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Satchu's Rich Wrap-Up
 
 
Tuesday 26th of May 2020
 
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Africa

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Apr 19 I was standing in front of the deserted streets of Gotham City at sunset; the sun shined thru darks clouds. @Nouriel
World Of Finance

New Yorkers are tough/resilient & most of us stayed in the city 2 survive & help in small or big ways (as any small act counts too) those who struggle rather than escape

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The Dollar Standard: The US Economy fell from 40% of World GDP in 1960 to just 25% today. However, 79.5% of all world trade is conducted in US dollars @RaoulGMI
World Currencies

The Dollar Standard: The US Economy fell from 40% of World GDP in 1960 to just 25% today. However, 79.5% of all world trade is conducted in US dollars. 84% of all non-domestic debt globally is US Dollar debt. Around $100trn of global debts are denominated in US Dollars.

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Total US domestic non-financial debts are $80 trn (and rising fast). The Fed balance sheet is currently $7 trn. @raoulGMI
U.S. Economy

If this recession is morphing into a global solvency event (which by definition is a slow miserable grind, not a shock and awe event, which is a liquidity event)

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When he is not lauded as "The Great Superforecasting Helmsman", the regime's eccentric and colourfully-robed leader often pretends he is a mere 'adviser', an absurd fiction
Law & Politics

When he is not lauded as "The Great Superforecasting Helmsman", the regime's eccentric and colourfully-robed leader often pretends he is a mere 'adviser', an absurd fiction that cowed members of the Politburo must nevertheless indulge on pain of liquidation.

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OCTOBER 30, 2014 BY DOMINIC CUMMINGS The Hollow Men II
Law & Politics


Blofeld: Kronsteen, you are sure this plan is foolproof? Kronsteen: Yes it is, because I have anticipated every possible variation of counter-move.

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India has technically been invaded by #China.@WPCION
Law & Politics


This is the Indian ITBP base at Finger 4, north bank of the Pangong Tso Lake, #Ladakh, #India 

China has occupied this base, built bunkers & even planted Chinese flag.

This is undisputed Indian territory.

This is happening right now.

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Why China’s Move to Rein In Hong Kong Is Just the Start @nytimes
Law & Politics




China’s move to strip away another layer of Hong Kong’s autonomy was not a rash impulse. It was a deliberate act, months in the making. 

It took into account the risks of international umbrage and reached the reasonable assumption that there would not be a significant geopolitical price to pay.

As a provocative move, it is just the latest.

With the world distracted by the pandemic’s devastating toll, China has taken a series of aggressive actions in recent weeks to flex its economic, diplomatic and military muscle across the region.

China’s Coast Guard rammed and sank a fishing boat in disputed waters off Vietnam, and its ships swarmed an offshore oil rig operated by Malaysia. 

Beijing denounced the second inauguration of Taiwan’s president, Tsai Ing-wen, and pointedly dropped the word peaceful from its annual call for unification with the island democracy.

Chinese troops squared off again last week with India’s along their contentious border in the Himalayas.



All are longstanding tensions, but the decision to impose new national security laws on Hong Kong, bypassing the semiautonomous territory’s own legislative process, shows what can happen with an unbridled China, no longer restrained by the fear of international rebuke.

“There was this idea before about China being cautious and trying to cultivate its soft power around the world,” said Jean-Pierre Cabestan, a professor at Hong Kong Baptist University and the author of “China Tomorrow: Democracy or Dictatorship?” “Those times are gone with Xi Jinping.”



Mr. Xi, who in seven years in power has pursued a “great rejuvenation” of the Chinese state, has emerged from the pandemic newly emboldened, seizing on nationalistic themes to deflect from the government’s early failures in stopping the coronavirus’s spread.

He still faces enormous economic and diplomatic challenges. New protests erupted in Hong Kong on Sunday, and resistance to greater control by Beijing could threaten the territory’s role as a financial center.

Officials and state media outlets have lashed out at the United States and other countries, accusing them of supporting “separatists” and “terrorists” in an effort to weaken the power of the Communist Party.




On the defensive over their handling of the virus, President Trump and his aides have sought to blame China for the pandemic’s toll in the United States. 

The criticism, by all appearances, has done little to moderate Mr. Xi’s actions. It may even have emboldened them, as Chinese officials point to the failures in the United States and other countries as evidence of the Communist Party’s better model of governance.

The Trump administration has, in turn, intensified its actions against China, imposing restrictions on trade and technology, praising Ms. Tsai’s inauguration and even marking the 25th anniversary of the disappearance of the 11th Panchen Lama, the second-highest figure in Tibetan Buddh



“The United States, in fact, is pouring oil on the fire, barrel by barrel,” Tian Feilong, a professor of law at Beihang University in Beijing, said in a telephone interview. 

“The central government is therefore actually just safeguarding its own most basic national security interests.”

China’s top diplomat, Wang Yi, said on Sunday that the two countries could still work together to promote global peace and stability, but he denounced those in the United States who seek American hegemony.

“It’s time for the United States to give up its wishful thinking of changing China,” Mr. Wang said, accusing American officials of having a Cold War mentality.

Mr. Xi’s move against Hong Kong has nonviolent echoes of President Vladimir V. Putin’s forceful seizure of Crimea from Ukraine in 2014, which was a violation of international law and of Russia’s previous diplomatic commitments. 

The annexation made Mr. Putin an international pariah for a while, but Russia still remains firmly in control of Crimea.


While Mr. Xi is using legislation rather than military force in a territory already under Chinese rule, it is nonetheless a brash move by an autocratic leader willing to risk international condemnation to resist what he views as foreign encroachment on his country’s security.

“The Communist Party doesn’t care anymore about the reactions, because it’s about survival, the stability of the one-party system, avoiding the fate of the Soviet Union,” Mr. Cabestan said. 

“Hong Kong is being perceived more and more as a base of surveillance, as a factor in the destabilization of the Chinese state.”




The challenges facing Mr. Xi come at a time when China’s major rivals, the United States above all, are in disarray, giving Mr. Xi more room to maneuver.

Britain, which is a signatory to the 1984 treaty that promised Hong Kong — its former colony — basic freedoms until 2047, issued a statement with Australia and Canada saying that they were “deeply concerned.” 

Senior Trump administration officials also denounced Mr. Xi’s gambit, warning that they could reconsider the territory’s special trade privileges or impose other sanctions. 

President Trump, whose few comments about Hong Kong have been inconsistent, said little.

For those who support Hong Kong’s unique status as Asia’s commercial and cultural crossroads, warnings no longer suffice in the face of determined pressure from Beijing.

Victoria Hui, a political scientist at the University of Notre Dame and author of a book on the 2014 Hong Kong protests known as the Umbrella Movement, said the international community had often spoken out against China’s steady accretion of power over the territory but had exacted no real punishment.


That has been the case for the most egregious violations of basic rights in Hong Kong in recent years, including extrajudicial kidnappings, excessive use of force by the police last year and the arrests of leading democratic leaders a week ago.

“The international pushback has been so weak,” Ms. Hui said. “Beijing is daring foreign governments to continue to issue words but take no actions.”

China’s tactics under Mr. Xi today contrast those of his immediate predecessors, who prioritized China’s reforms and opening over confrontation with its neighbors or the broader world. 

“Hide our strength, bide our time” was Deng Xiaoping’s adage a generation ago.

When Taiwan was moving to hold its first presidential elections in 1996, China conducted intimidating missile tests in the Taiwan Strait. 

It was forced to back down when President Bill Clinton ordered American aircraft carriers to the waters in a show of military support for the island’s defense.

Mr. Xi has steadily built up China’s air and naval power, making a similar move by the United States today much riskier. 

Chinese forces routinely menace the island, as its first operational aircraft carrier did last month, forcing Taiwan’s military to scramble jets and ships. 

The seventh similar incident this year, it signaled China’s determination to block Taiwan from formally establishing its independence.




For Beijing’s leaders, China’s sovereignty over Hong Kong is as emotionally charged.

Under the Basic Law, the mini-constitution that governs the territory, Hong Kong is obliged to adopt rules “to prohibit any act of treason, secession, sedition and subversion” against the Chinese government. 

When the city’s legislature tried to do so in 2003, Beijing retreated in the face of huge street protests.

“China was in a very different place globally,” said Rana Mitter, the director of the University of Oxford China Center. 

“China’s economy was growing in 2003, but it wasn’t the second biggest economy in the world and quite the economic behemoth it is today.”

There is also a more subtle difference that the pandemic has accentuated. Beijing spent years deflecting criticism of its system by saying that China was not yet ready for more democratic freedoms, effectively leaving open the possibility for greater liberalization of the political system, as many inside and outside the country hoped.

China, Mr. Mitter said, is now a “state which no longer apologizes for being authoritarian.”

On Friday, Mr. Xi told delegates at the annual session of the legislature, the National People’s Congress, that the country’s system was the “the broadest, most genuine, and most effective democracy to safeguard the fundamental interests of the people.”

Such confidence has allowed Mr. Xi to brush aside international concerns about China’s behavior at home and abroad: the absence of government transparency and accountability, the countless arrests of those who express dissent, the mass detention of more than one million Uighurs and other Muslims in the western province of Xinjiang.

It has also emboldened China in ways that create the possibility of armed conflict.

On the remote border with India, Chinese forces have twice in the last month clashed with Indian troops, prompting both sides to send in re-enforcements. India has accused China of blocking patrols on its side on the Line of Control, the unofficial border.

China has also stepped up its efforts to dominate the South China Sea despite the territorial claims of countries like Vietnam, Malaysia and the Philippines.

In April, it created two new administrative districts to govern the islands it controls in the Paracel and Spratly chains. China’s Navy also said that it had succeeded in growing cabbage and other vegetables in the sand of Woody Island, helping to feed the growing number of troops stationed there.


“Chinese aggression is not always just rhetorical,” Alice G. Wells, an assistant U.S. Secretary of State, said in a telephone briefing in Washington last week.

“So whether it’s in the South China Sea or whether it’s along the border with India,” she said, “we continue to see provocations and disturbing behavior by China that raises questions about how China seeks to use its growing power.”



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07-OCT-2019 :: Joshua Wong told German Media "Hongkong ist das neue Berlin"
Law & Politics


“The Folks in Hong Kong [whom Xi is seeking to unmask so he can exercise algorithmic control over them] are in open rebellion. 

Joshua Wong told German Media “Hongkong ist das neue Berlin” referencing the “Ich bin ein Berliner” speech given by United States President John F. Kennedy on June 26, 1963, in West Berlin.

I am sure Xi sees Hong Kong and Taiwan like a virus and he is looking to impose a quarantine just like he has imposed on Xinjiang. 

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”No force can stop the Chinese people and the Chinese nation forging ahead”, he said
Law & Politics

“Unity is iron and steel; unity is a source of strength,” “Complete reunification of the motherland is an inevitable trend..no one and no force can ever stop it!” he added.

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However, no direct ancestral virus or intermediate host for the cross-species transmission of SARS-CoV-2 to humans has yet been identified.
Market Crashes / Panic


Notably, efficient human to human transmission appears to have occurred as soon as the outbreak of SARS-CoV-2 was recognized 

Human angiotensin-converting enzyme 2 (ACE2) has been identified as the receptor for the spike protein of SARS-CoV-2 and virus entry is also facilitated by the serine protease TMPRSS2 [5,9-11]. 

By sequence comparison, we found that the spike protein of SARS-CoV-2 is closely related to that of a bat coronavirus, RaTG13 [6], while other parts of the viral genome are more distantly linked [7]. 

Interestingly, an additional polybasic cleavage motif, PRRA, is found in the S1/S2 cleavage site of SARS-CoV-2 spike protein, but not in the bat coronavirus strain, RaTG13 [12]. 

Previous studies have shown that protease-mediated entry is one of the determinants of success in SARS coronavirus infection [13,14]. 

It is speculated that the acquisition of mutations or additional motifs to facilitate S1/S2 cleavage may enhance SARS-CoV-2 infection in humans.

Human angiotensin-converting enzyme 2 (ACE2) has been identified as the receptor for the spike protein of SARS-CoV-2 and virus entry is also facilitated by the serine protease TMPRSS2 [5,9-11]. 

By sequence comparison, we found that the spike protein of SARS-CoV-2 is closely related to that of a bat coronavirus, RaTG13 [6], while other parts of the viral genome are more distantly linked [7]. 

Interestingly, an additional polybasic cleavage motif, PRRA, is found in the S1/S2 cleavage site of SARS-CoV-2 spike protein, but not in the bat coronavirus strain, RaTG13 [12].
Previous studies have shown that protease-mediated entry is one of the determinants of success in SARS coronavirus infection [13,14]. 

It is speculated that the acquisition of mutations or additional motifs to facilitate S1/S2 cleavage may enhance SARS-CoV-2 infection in humans.

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We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans
Market Crashes / Panic


We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, 




Introduction

Three coronaviruses have crossed the species barrier to cause deadly pneumonia in humans since the beginning of the 21st century: severe acute respiratory syndrome coronavirus (SARS-CoV) (Drosten et al., 2003, Ksiazek et al., 2003), Middle-East respiratory syndrome coronavirus (Zaki et al., 2012) (MERS-CoV), and SARS-CoV-2 (Huang et al., 2020, Zhu et al., 2020). SARS-CoV emerged in the Guangdong province of China in 2002 and spread to five continents through air travel routes, infecting 8,098 people and causing 774 deaths. In 2012, MERS-CoV emerged in the Arabian Peninsula, where it remains a major public health concern, and was exported to 27 countries, infecting a total of ∼2,494 individuals and claiming 858 lives. A previously unknown coronavirus, named SARS-CoV-2, was discovered in December 2019 in Wuhan, Hubei province of China and was sequenced and isolated by January 2020 (Zhou et al., 2020, Zhu et al., 2020). SARS-CoV-2 is associated with an ongoing outbreak of atypical pneumonia (Covid-2019) that has affected over 90,000 people and killed more than 3,000 of those affected in >60 countries as of March 3, 2020. On January 30, 2020, the World Health Organization declared the SARS-CoV-2 epidemic a public health emergency of international concern.

In addition to the highly pathogenic zoonotic pathogens SARS-CoV, MERS-CoV, and SARS-CoV-2, all belonging to the β-coronavirus genus, four low-pathogenicity coronaviruses are endemic in humans: HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E. To date, no therapeutics or vaccines are approved against any human-infecting coronaviruses.


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Origin of #COVID19
Market Crashes / Panic


“If they can get you asking the wrong questions, they don't have to worry about answers.”


 “There's always more to it. This is what history consists of. It is the sum total of the things they aren't telling us.”

“A paranoid is someone who knows a little of what's going on. ”


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'One thing people need to know is that Google is a vaccine company...They're partnering w/all the pharma cos...a $761 million partnership w/Glaxo. harvesting medical information...all turned into sellable data.'@robertkennedyjr
Information & Communication Technology

"One thing people need to know is that Google is a vaccine company...They're partnering w/all the pharma cos...Google has a $761 million partnership w/Glaxo. What they're doing is harvesting medical information...all turned into sellable data." @robertkennedyjr #MalkinLive

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Coronavirus is 'uniquely adapted to infect humans': Top vaccine scientist says it could only have come from an animal through a 'freak of nature' - and the possibility it leaked from Wuhan lab MUST be investigated @MailOnline
Market Crashes / Panic


A team of scientists has produced evidence that the pandemic virus is ‘uniquely adapted to infect humans’, raising fresh questions over whether its origins were natural or could have occurred in a laboratory.

Professor Nikolai Petrovsky, a top vaccine researcher who headed the Australian team, said the virus was ‘not typical of a normal zoonotic [animal to human] infection’ since it appeared with the ‘exceptional’ ability to enter human bodies from day one.

He said the virus should have emerged from an animal through ‘a freak event of nature’ but the possibility that it had leaked from a laboratory could not be ruled out.

Petrovsky, professor of medicine at Flinders University in Adelaide, runs a biotech research unit that will start human trials for a Covid-19 vaccine next month.

‘I haven’t seen a zoonotic virus that has behaved in this way before,’ he said.

He told The Mail on Sunday that new viruses crossing over from animals normally strengthen as they adapt to human hosts, but for unexplained reasons, this new coronavirus seems perfectly adapted to infect humans without the need to evolve.


He pointed to the ‘coincidence’ that the most closely related known viruses were being studied in a laboratory in Wuhan, the Chinese city where the pandemic erupted, and insisted that the possibility of a leak, however remote, should not be ignored in the search for its origin.

‘The implications may not be good for scientists or global politics, but just because the answers might cause problems, we can’t run away from them,’ he added. ‘There is currently no evidence of a leak but enough circumstantial data to concern us. It remains a possibility until it is ruled out.’

Prof Petrovsky has gone further than any other expert in raising the idea that the virus escaped from one of two laboratories researching bat viruses in Wuhan.

Richard Ebright, one of the world’s top biosecurity experts, also told this newspaper that the odds of this new virus containing such unusual features and occurring naturally were ‘possible – but improbable’.

Ebright, professor of chemical biology at Rutgers University, in New Jersey, said scientists at the Wuhan Institute of Virology were creating chimeric coronaviruses (new hybrid micro-organisms) and seeking funding to test their ability to infect human cells while using procedures that leave no sign of human manipulation.

Asked about the chance of a leak, he replied: ‘There definitely is a possibility. But there is no basis to say a high probability.’

Last week, the MoS revealed details of a key study challenging China’s claims that the pandemic emerged from a Wuhan animal market in December. The researchers were ‘surprised’ to find the virus ‘already pre-adapted to human transmission’, contrasting its stability with another coronavirus that evolved rapidly as it spread around the planet during the 2002-04 SARS epidemic. 

Their findings are backed by the Australian team’s study into the ‘spike protein’ that binds Sars-CoV-2 – the new strain of coronavirus that causes disease – to cells in human bodies. 

The research, posted on Cornell University’s website but not yet peer-reviewed, used computer modelling to test the spike protein’s ability to bind to humans and 12 possible animal hosts.

It found the ability to bind to human cells far exceeded its ability in other species. ‘This indicates Sars-CoV-2 is a highly adapted human pathogen,’ it said, ‘raising questions as to whether it arose in nature by a rare chance event or whether its origins lie elsewhere.’

Prof Petrovsky said it seemed ‘very unusual’ for an ‘exquisitely human adaptive virus’ to have suddenly crossed from an animal host to humans last year.



‘This is either a remarkable coincidence or a sign of human intervention,’ he said. ‘It is possible the virus was a fluke event and it turns out humans were the perfect host.

‘But we don’t have evidence for this because no one has found this virus in an intermediate host animal [for example pangolin] yet.

‘No one can say a laboratory leak is not a possibility.’

He claimed that scientists were reluctant to discuss the possibility of botched lab experiments or leaks since any backlash could lead to research restrictions and threaten crucial research. However, he added, it was vital to discover the source of the virus.

Prof Petrovsky said that if Sars-CoV-2 was a natural event, another related virus could erupt again from the same source with even more devastating consequences. 

‘Next time, it could have far worse mortality rates,’ he warned.

He also highlighted the ‘furin cleavage site’, which allows the spike protein to bind to cells in human tissues including the lungs, liver and small intestines.


Previous studies have noted the efficiency of this cleavage method, which does not exist in the most similar coronaviruses – although researchers in 2009 modified the SARS virus to introduce a furin cleavage site in a similar position to Sars-CoV-2 and found this increased the infectivity of the virus.


In the latest study published on Friday, three German scientists highlighted how this cleavage site was essential for the infection of human lung cells. 

One US expert in biomedical sciences, who did not wish to be named, said there was no direct evidence to support the idea that the virus was engineered or leaked from a lab, although ‘the location of the acquired furin mutation is quite surprising’.

Another leading research scientist said a member of his team ‘went a bit pale when he looked at this’.

A paper earlier this year by Yong-Zhen Zhang, the Chinese diseases expert who published the first genome sequence for Sars-CoV-2, said this was ‘arguably the most important’ difference between the new virus and its closest known relative, which was derived from a bat by Wuhan researchers.

Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris, said the ‘body of evidence’ suggested this was a natural virus. ‘You would see signatures if this was an engineered virus and I don’t see any evidence that it is engineered,’ he said.

Last week Chinese health officials confirmed they had ordered some labs to destroy samples of the coronavirus to ensure work was not being carried out in units that did not meet global biosafety rules.

Wuhan virus lab was signed off by EU Brexit chief Michel Barnier in 2004 - despite French intelligence warnings that China's poor bio-security reputation could lead to a catastrophic leak 

The construction of the Chinese laboratory at the centre of mounting suspicion over the source of the Covid-19 pandemic was signed off by the EU’s chief Brexit negotiator Michel Barnier – despite warnings by French intelligence services.

Mr Barnier – currently embroiled in acrimonious negotiations with the UK over a post-Brexit trade deal – was the French foreign minister when he gave the go-ahead for work to start on the Wuhan Institute of Virology in 2004, under a joint deal with the Chinese.

The move came despite strong opposition from French diplomatic and security advisers, who argued that the Chinese reputation for poor bio-security could lead to a catastrophic leak.

They also warned that Paris could lose control of the project, and even suggested that Beijing could harness the technology to make biowarfare weapons.

Eleven years later, as the laboratory prepared to open, the French architects of the project complained that they had, as feared, been ousted by the Chinese communist government.



Mr Barnier’s role in helping to establish the Wuhan institute can be revealed as part of a Mail on Sunday investigation into French connections to the laboratory.

The site was carrying out research on coronaviruses when the outbreak started in the city last November.

A growing number of scientific and security experts are now questioning the Chinese government’s insistence that the virus originated in a wildlife market in Wuhan, with Beijing’s refusal to allow an international investigation only adding to the growing suspicions.

Last week, The Mail on Sunday revealed that experts now believe the coronavirus was taken into the market by someone already carrying the disease.

Biologists who carried out a landmark study say they were ‘surprised’ to find the virus was ‘already pre-adapted to human transmission’.

Jacques Chirac, the French president at the time of the deal, pushed for the Wuhan institute to be set up after the 2003 SARS outbreak, which affected 26 countries and resulted in more than 8,000 cases and 774 deaths. 

Mr Chirac, along with his pro-Beijing prime minister Jean-Pierre Raffarin, promised French funding and expertise in return for a share of the intellectual copyright on the lab’s discoveries.

They argued that a French-Chinese collaboration could develop effective – and lucrative – vaccines to prevent a repeat of a deadly virus pandemic.


France is a global leader in virus research, but the Chirac government also saw the deal as a way to forge stronger trade links with China than its Western rivals.

According to a report in France’s Le Figaro newspaper, institutions such as the General Directorate for External Security, the French equivalent of MI6, expressed repeated concern at the lack of international control over Chinese laboratories and issues with ‘transparency’.

A source told the newspaper: ‘What you have to understand is that a P4 [high-level bio-security] laboratory is like a nuclear reprocessing plant. It’s a bacteriological atomic bomb.

‘The viruses that are tested are extremely dangerous – diving suits, decontamination airlocks etc must be followed to the letter.’

As part of the deal, up to 50 French scientists were expected to travel to Wuhan to help the Chinese run the laboratory properly – but they never went.



Alain Merieux, the French billionaire who was instrumental in setting up the Wuhan laboratory in partnership with his Institut Merieux in Lyons, abandoned the project in 2015, saying: ‘I am giving up the co-chairmanship of [the] P4 [laboratory], a Chinese tool. It belongs to them, even if it was developed with technical assistance from France.’


According to Le Figaro, a diplomat with a close knowledge of the deal added: ‘We knew the risks involved and thought that the Chinese would control everything and quickly eject us from the project.

‘We believed that providing this cutting-edge technology to a country with an endless power agenda would risk exposing France in return.’

Their fears were compounded in 2015 when China implemented a new policy of ‘dual use’ technologies, which allows their armed forces to use any civilian technology for military purposes.

The Wuhan institute became operational in January 2018, and coincided with a visit to Beijing by current French president Emmanuel Macron and Mr Raffarin, who was made a ‘special envoy to China’.

Last night, a Foreign Ministry source in Paris confirmed that Mr Barnier had helped set up the Wuhan institute when he was foreign minister as ‘the hand that signed the paper’.


Mr Barnier, a Gaullist conservative, served as foreign minister for just over a year, from April 2004 to June 2005.


The source said: ‘The aim was to develop vaccines following the SARS crisis between 2002 and 2004.

‘There was much co-operation on a range of issues between France and China at the time, and Michel Barnier was implementing government policy.’

The source added that opposition to the move had come from a number of people, including senior figures within the French security services.

‘The issue of bio-security was certainly a cause for concern within agencies including the DGSE,’ said the source.

A security services source involved in the case at the time said: ‘The Chinese laboratories were not inspiring a great deal of trust, but the government had its own reasons for progressing with this.’ 

World Health Organisation hails 'goodwill ambassador' Peng Liyuan on its website as a singing star... but fails to mention she's the wife of China's President, amid concerns over WHO'S handling of the coronavirus pandemic

Peng Liyuan is listed on the World Health Organisation’s website alongside former Liberian president Ellen Johnson Sirleaf and Liverpool goalkeeper Alisson Becker as one of nine ‘goodwill ambassadors’.

When she was appointed, the then-head of the WHO hailed the Chinese folk singer’s ‘world famous voice and her compassionate heart’, saying she was ‘a big bright star with a huge and respectful audience of admirers’.

There was, however, no mention of the other reason why Peng is so well known – she is the wife of Xi Jinping, President of China and leader of its Communist Party.


Peng, who holds the rank of major-general in the army, sang in uniform for soldiers after they crushed pro-democracy protests in Tiananmen Square – although state censors have sought to scrub these pictures from the internet.

The revelation that China’s first lady has been serving in such a prominent role will fuel pressure on the WHO, which has been criticised during the pandemic – sparked by concerns over its current boss’s close relationship with Beijing.

‘The definition of goodwill seems to be stretched,’ said Tory MP Tom Tugendhat, chairman of the Foreign Affairs Committee. ‘The WHO should choose people who champion the rights of those they’re there to serve, not those whose record leaves their commitment in doubt.’

Peng, who joined the People’s Liberation Army in 1980, made her name on China’s state-run television as a singer of syrupy songs praising the Communist Party and her country’s rise to power.



She married Xi in 1987, when he was the divorced deputy mayor of the city of Xiamen. She was appointed by Margaret Chan, China’s first head of a United Nations body, who has since joined a key Communist Party policy body.

Peng was reappointed to the WHO by Chan’s successor Tedros Adhanom Ghebreyesus, who also tried to hand one of the posts to Zimbabwean dictator Robert Mugabe before outrage forced a retreat.

Peng has attended influential summits and has joined her husband at key UN meetings. She has also met Bill Gates, the billionaire philanthropist who bailed out the WHO after its funding was cut by the US in fury over its pro-China stance. Donald Trump has called the WHO a ‘pipe organ’ for Beijing’s interests.

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The Lancet article included the genome, I put a red box around the two segments that are the Frankenstein-bits of the puzzle, one segment from a bat 900 miles away. @davegreenidge57
Market Crashes / Panic

The Lancet article was how most of the world learned early on that #COVIDー19 didn’t originate in the market as assumed. The article included the genome, I put a red box around the two segments that are the Frankenstein-bits of the puzzle, one segment from a bat 900 miles away.

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In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus @Cornell
Market Crashes / Panic


Abstract

The devastating impact of the COVID-19 pandemic caused by SARS–coronavirus 2 (SARS- CoV-2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in SARS-CoV-2 susceptibilities across animal species. Traditional lab-based methods will ultimately answer many of these questions but take considerable time. Increasingly powerful in silico modeling methods provide the opportunity to rapidly generate information on newly emerged pathogens to aid countermeasure development and also to predict potential future behaviors. We used an in silico structural homology modeling approach to characterize the SARS-CoV-2 spike protein which predicted its high affinity binding to the human ACE2 receptor. Next we sought to gain insights into the possible origins and transmission path by which SARS-CoV-2 might have crossed to humans by constructing models of the ACE2 receptors of relevant species, and then calculating the binding energy of SARS-CoV-2 spike protein to each of these. Notably, SARS-CoV-2 spike protein had the highest overall binding energy for human ACE2, greater than all the other tested species including bat, the postulated source of the virus. This indicates that SARS-CoV-2 is a highly adapted human pathogenOf the species studied, the next highest binding affinity after human was pangolin, which is most likely explained by a process of convergent evolution. Binding of SARS-CoV-2 for dog and cat ACE2 was similar to affinity for bat ACE2, all being lower than for human ACE2, and is consistent with only occasional observations of infections of these domestic animals. Snake ACE2 had low affinity for spike protein, making it highly improbable that snakes acted as an intermediate vector. Overall, the data indicates that SARS-CoV-2 is uniquely adapted to infect humans, raising important questions as to whether it arose in nature by a rare chance event or whether its origins might lie elsewhere.



Introduction

The devastating impact of COVID-19 infections caused by SARS–coronavirus 2 (SARS-CoV-2) has stimulated unprecedented international activity to discover effective vaccines and drugs for this and other pathogenic coronaviruses.1-16 It has also raised important questions on the mechanisms of zoonotic transfer of viruses from animals to humans, questions as to whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in SARS-CoV-2 susceptibility across animal species.17-19 Understanding how viruses move between species may help us prevent or minimize these pathways in the future. Elucidating the molecular basis for the different susceptibilities of species may also shed light on the differences in susceptibilities in different sub-groups of humans.
Very recently, Shi et al. published the results of experiments to determine the susceptibility to SARS-CoV-2 of ferrets, cats, dogs, and other domesticated animals.20 They showed that SARS- CoV-2 virus replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. Other studies have reported the susceptibility of other animal species to SARS-CoV-2.17,20,21 Susceptible species such as macaques, hamsters and ferrets are used as animal models of SARS-CoV-2 infection.22-24 In the absence of purified, isolated ACE2 from all the relevant animal species that could be used to measure the molecular affinities to spike protein experimentally, computational methods offer considerable promise for determining the rank order of affinities across species, as a method to impute which species may be permissive to SARS-CoV-2.
Here we show how computational chemistry methods from structure-based drug design can be used to determine the relative binding affinities of the SARS-CoV-2 spike protein for its receptor, angiotensin converting enzyme (ACE)-2, a critical initiating event for SARS-CoV-2 infection, across multiple common and exotic animal species.25-27 The aim of these studies was to better understand the species-specific nature of this interaction and see if this could help elucidate the origin of SARS-CoV-2 and the mechanisms for its zoonotic transmission.
Materials and Methods
Homology modelling of structures
To construct the three-dimensional structure of the SARS-CoV-2 spike protein, the sequence was retrieved from NCBI Genbank Database (accession number YP_009724390.1). A PSI-BLAST search against the PDB Database for template selection was performed and the X-ray structure of SARS coronavirus spike template (refcode 6ACC) was selected with 76.4% sequence similarity to SARS-CoV-2 spike protein. The protein sequences of the ACE2 proteins for different species is summarized in Table 11 and full sequence alignment in Supplementary Figure 1. The phylogenetic tree for ACE2 proteins from selected animal species is illustrated in Supplementary Figure 2. The 3D-structures were built using Modeller 9.21 (https://salilab.org/modeller/).28 The quality of the generated models was evaluated using the GA341 score and DOPE scores, and the models assessed using SWISS-MODEL structure assessment server (https://swissmodel.expasy.org/assess).29
Protein Structure preparation
The X-ray crystal structures of human ACE2 (recode 3SCI) and human SARS spike protein (refcode 5XLR) were retrieved from Protein Data Bank. Protein preparation and removal of non- essential and non-bridging water molecules for docking studies were performed using the UCSF Chimera package (https://www.cgl.ucsf.edu/chimera/).30
Molecular Docking
These modelled structures were docked against SARS-CoV-2 spike protein structure using the HDOCK server (http://hdock.phys.hust.edu.cn/).31,32 Molecular docking was performed on the homology modelled SARS-CoV-2 spike protein with human and animal ACE2 proteins. The SARS-CoV spike protein was also docked with human ACE2 protein to obtain the docking pose for binding energy calculations. The docking poses were ranked using an energy-based scoring function. The docked structures were analyzed using UCSF Chimera software.
Molecular Dynamics Simulation
The final models were optimized using the AMBER99SB-ILDN force field in Gromacs2020 (http://www.gromacs.org/).33 Docked complexes (SARS-CoV-2 spike with human ACE2, human
SARS-CoV spike with human ACE2, SARS-CoV-2 spike with bat ACE2 etc) were used as starting geometries for MD simulations. Simulations were carried out using the GPU accelerated version of the program with the AMBER99SB-ILDN force field I periodic boundary conditions on an Oracle Cloud Server. Docked complexes were immersed in a truncated octahedron box of TIP3P water molecules. The solvated box was further neutralized with Na+ or Cl− counter ions using the tleap program. Particle Mesh Ewald (PME) was employed to calculate the long-range electrostatic interactions. The cutoff distance for the long-range van der Waals (VDW) energy term was 12.0 Å. The whole system was minimized without any restraint. The above steps applied 2500 cycles of steepest descent minimization followed by 5000 cycles of conjugate gradient minimization. After system optimization, the MD simulations was initiated by gradually heating each system in the NVT ensemble from 0 to 300 K for 50 ps using a Langevin thermostat with a coupling coefficient of 1.0/ps and with a force constant of 2.0 kcal/mol·Å2 on the complex. Finally, a production run of 100 ns of MD simulation was performed under a constant temperature of 300 K in the NPT ensemble with periodic boundary conditions for each system. During the MD procedure, the SHAKE algorithm was applied for the constraint of all covalent bonds involving hydrogen atoms. The time step was set to 2 fs. The structural stability of the complex was monitored by the RMSD and RMSF values of the backbone atoms of the entire protein. Finally, the free energies of binding were calculated for all the simulated docked structures. Calculations were also performed for up to 500 ns on human ACE2 to ensure that 100ns is sufficiently long for convergence. Duplicate production runs starting with different random seeds were also run to allow estimates of binding energy uncertainties to be determined for the strongest binding ACE2 structures.
MM‐PBSA binding free energy study
The binding free energies of the protein‐protein complexes were evaluated in two ways. The traditional method is to calculate the energies of solvated SARS-CoV-2 spike and ACE2 proteins and that of the bound complex proteins and derive the binding energy by subtraction.
ΔG (binding, aq) = ΔG (complex, aq) – (ΔG (spike, aq) + ΔG (ACE2, aq) (1)
We also calculated binding energies using the molecular mechanics Poisson Boltzmann surface area (MM-PBSA) tool in GROMACS that is derived from the nonbonded interaction energies of the complex.34,35 The method is also widely used method for binding free energy calculations. The binding free energies of the protein complexes were analyzed during equilibrium phase from the output files of 100 ns MD simulations. The g_mmpbsa tool in GROMACS was used after molecular dynamics simulations, the output files obtained were used to post-process binding free energies by the single-trajectory MM-PBSA method. Specifically, for a non-covalent binding interaction in the aqueous phase the binding free energy, ΔG (bind,aq), is: –
ΔG (bind,aqu) = ΔG (bind,vac) + ΔG (bind,solv) (2)
where ΔG (bind,vac) is the binding free energy in vacuum, and ΔG(bind,solv) is the solvation free energy change upon binding: –
ΔG (bind,solv) = ΔG (R:L, solv) - ΔG (R,solv) - ΔG (L,solv) (3)
where ΔG (R:L,solv), ΔG (R,solv) and ΔG (L,solv) are solvation free energies of complex, receptor and ligand, respectively.
Free energy decomposition analyses were also performed by MM-PBSA decomposition to get a detailed insight into the interactions between the ligand and each residue in the binding site. The binding interaction of each ligand–residue pair includes three terms: the van der Waals contribution, the electrostatic contribution, and the solvation contribution.
Interaction energy
Another estimate of the strength of the interaction between protein-protein complex can be obtained from the non-bonded interaction energy between the complex. GROMACS has the ability to decompose the short-range nonbonded energies between any number of defined groups. To compute the interaction energies as a part of our analysis, we reran the trajectory files obtained during simulation to recompute energies using -rerun command. The interaction energy is the combination of short range Coulombic interaction energy (Coul-SR:Protein-Protein) and the short-range Lennard-Jones energy (LJ-SR:Protein-Protein (see Table 3).
While this paper was being prepared, a paper by Guterres and Im described a substantial improvement in protein-ligand docking results using high-throughput MD simulations.36 They employed docking using AutoDock Vina, followed by MD simulation using CHARMM. The parameters they advocated were very similar to those used in our study. Proteins were solvated in a box of TIP3P water molecules extending 10 Å beyond the proteins and the particle-mesh Ewald method was used for electrostatic interactions. Nonbonded interactions over 10 and 12 Å were truncated. Their systems were minimized for 5000 steps using the steepest descent method followed by 1 ns equilibration with an NVT setting. For each protein-ligand complex, they ran 3 × 100 ns production runs from the same initial structure using different initial velocity random seeds and an integration step size of 2 fs.Results
The ancestry of SARS-CoV-2 traces back to the human, civet and bat SARS-CoV strains, which all use the same ACE2 proteins for cellular entry.37-39 The similarities and variations in sequences for both the SARS-CoV-2 spike protein and the SARS spike protein were determined from sequences retrieved from NCBI GenBank Databank and aligned using CLUSTALW. The spike protein receptor binding domain (RBD) region showed a 72% identity between the two viruses (Figure 1).

Discussion
Knowing which species may be permissive to SARS-CoV-2 is very important, both in respect of identifying intermediate hosts and potential source of the original virus, as well as helping to identify suitable species for use as infection models to allow testing of COVID-19 drugs and vaccines. Directly testing broad ranges of species for virus susceptibility is difficult and time consuming and in the cases of very rare species, may not even be practicable. A less direct method to try and obtain the same information might involve measurement of binding affinity of the SARS- CoV-2 spike protein to the target ACE2 receptor from different species. This can be done, for example, through use of cell lines transfected with ACE2 receptors from each individual species, but this would again be time consuming and not practicable. A third approach, adopted here, is to use fast, efficient in silico structural modelling and docking algorithms, using available genomic and structural biology data, to generate relevant ACE2 structural models and use molecular dynamics to calculate the binding energies. Notably, this approach surprisingly revealed that the binding energy between SARS-CoV-2 spike protein and ACE2 was highest for humans out of all species tested, suggesting that SARS-CoV-2 spike protein is uniquely evolved to bind and infect cells expressing human ACE2. This finding is particularly surprising as, typically, a virus would be expected to have highest affinity for the receptor in its original host species, e.g. bat, with a lower initial binding affinity for the receptor of any new host, e.g. humans. However, in this case, the affinity of SARS-CoV-2 is higher for humans than for the putative original host species, bats, or for any potential intermediary host species.
The calculated binding energies of SAR-Cov2 spike protein with ACE2 from selected species are in general agreement with the relatively limited amount of published information. SAR-Cov2 binding affinity to monkey ACE2 was lower than for human ACE2. Young cynomolgus macaques when infected expressed viral RNA in nasal swabs but did not develop overt clinical symptoms whereas aged animals showed higher viral RNA loads and some weight loss and rapid respiration associated with moderate interstitial pneumonia and virus replication in upper and lower respiratory tract.23,48 Syrian hamsters and ferrets are highly susceptible to SARS-CoV infection and are used as animal models of the disease. Mahdy published a preprint reviewing SARS-CoV-2 infection in animals and suggested that SARS-CoV-2 might recognize ACE2 from a variety of animal species, including palm civet, the intermediate host for SARS-CoV. 45
Although bats carry many coronaviruses including SARS-CoV, a relative of SARS-CoV-2, direct evidence for existence of SARS-CoV-2 in bats has not been found. As highlighted by our data, the binding strength of SARS-CoV-2 for bat ACE2 is considerably lower than for human ACE2suggesting that even if SARS-CoV-2 did originally arise from a bat precursor it must later have adapted its spike protein to optimise its binding to human ACE2There is no current explanation for how, when or where this might have happened. Instances of direct human infection by coronaviruses or other bat viruses is rare with transmission typically involving an intermediate host. For example, lyssaviruses such as Hendra are periodically transmitted from bats to horses and then to humans who contact the infected horse. Similarly, SARS-CoV was shown to be transmitted from bats to civet cats and from them to humans. To date, a virus identical to SARS-CoV-2 has not been identified in bats or any other non-human species, making its origins unclear. To date, the most closely related coronavirus to SARS-CoV-2, is the bat coronavirus, BatCoV RaTG1, which has 96% whole-genome identity to SARS-CoV-2.50. The fact that SARS-CoV-2 has also not been found in any likely intermediate host raises questions of the origins of the original SARS-CoV-2 virus that infected human case zero in late 2019. Wuhan, the epicentre of the outbreak, hosts China’s only BSL4 facility and is the site of considerable bat coronavirus research. Identification of an intermediate animal host in which SARS-CoV-2 might have adapted to a human ACE2 permissive form would go a long way to alleviating concerns that SARS-CoV-2 is not a natural virus. Lam et al.44 made confused public claims of finding SARS-CoV-2 in Malayan pangolins, suggesting that pangolins were an intermediate vector for SARS-CoV-2. However, further sequence analysis of these claims by Zhang et al. established that Pangolin-CoV was a very different coronavirus that had modest at best ~90% sequence similarity to SARS-CoV-2While Pangolin- CoV spike RBD shared some similarities to SARS-CoV-2, its spike protein did not share the furin cleavage site that was a prominent feature of SARS-CoV-2 spike protein.51 Hence, any similarity of Pangolin-CoV to SARS-CoV-2 was restricted to the residues in the RBD and RBM. Overall, Pangolin-CoV is only a distant relative of SARS-CoV-2.
Based on our data, the similarity of Pangolin-CoV to SARS-CoV-2 in the spike RBM could be a case of convergent evolution of the two viruses, whereby the close similarity of the structure of the pangolin ACE2 spike binding domain (SBD) to the same region of human ACE2, drove the convergent evolution of the spike protein RBD of both viruses, allowing them to bind to pangolin and human ACE2, respectively. Such close similarity of pangolin and human ACE2 SBD could make it easy for any pangolin CoV to cross from pangolins to humans. Nevertheless, with no virus matching the SARS-CoV-2 sequence identified in pangolins this makes it less likely that SARS- CoV-2 has a pangolin originHowever, this does call for more intensive survey of coronaviruses in pangolin populations, should such viruses pose future human pandemic threats. This finding also supports the need for strict enforcement of a worldwide ban on any trafficking of pangolins to reduce risks of pangolin coronaviruses crossing to humans and becoming a trigger for a future coronavirus pandemic. However, there continues to be a lack of evidence to indicate that SARS- CoV-2 is a pangolin-derived virus that first crossed from pangolins to humans in late 2019.
Early in the COVID-19 outbreak it was suggested that snakes may be an intermediate vector. ACE2 of turtle and snake has very low homology to human ACE2 and SARS-CoV-2 was shown to not bind to reptile ACE2, making snakes unlikely as possible hosts for SARS-CoV-2. 46 This is consistent with our own data predicting moderate to low binding of SARS-CoV-2 to snake ACE2. Rodents varied widely in their permissiveness to SARS-CoV with mice being resistant and hamsters permissive. Similarly there is inefficient virus replication of SARS-CoV-2 in mice making them unsuitable as models to test SARS or COVID-19 vaccines or drugs. 47 This reflects the low predicted binding energy of SARS-CoV-2 spike protein for mouse ACE2, as demonstrated by our model data. Mice only became permissive for SARS infection when made transgenic for human ACE2, with the same likely to be true for SARS-CoV-2. By contrast, hamsters were highly permissive for SARS-CoV infection. Our model predicted that hamster should be permissive to SARS-CoV-2 infection based on the predicted strong binding of SARS-Cov-2 spike protein for hamster ACE2 (Table 4). Consistent with our model data, Syrian hamsters have been shown to exhibit clinical and histopathological responses to SARS-CoV-2 that closely mimic human upper and lower respiratory tract infections, with high virus shedding and ability to transmit to naïve contact animals.24 Ferrets were another permissive model of SARS CoV infection, and our modelling data indicated that SARS-CoV-2 has a similar binding energy to ferret, as it does to hamster, ACE2 (Table 4). Consistent with our model data, ferrets have been shown to be permissive to infection with SARS-CoV-2, with high virus titre in the upper respiratory tract, virus shedding, infected ferrets showing acute bronchiolitis but without severe disease or death, and active transmission to naïve ferrets through direct contact.20,22
Cat and tiger ACE2 were shown by our model to have similar binding affinity for SARS-CoV-2 spike protein and both these species have been shown to be permissive for SARS-CoV-2 infection. Similarly our data suggests that SARS-CoV-2 binds with moderate affinity to dog ACE2 suggesting that dogs may be susceptible to infection by SARS-CoV-2. In the case of companion animals that live in close proximity to humans, Shen at al. state that SARS-CoV-2 can be efficiently transmitted in cats and dogs while Shi et al. found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but that ferrets and cats were permissive to infection. Temmam et al. tested 9 cats and 12 dogs living in close contact with their owners, two of whom tested positive for SARS-CoV-2 and 11 of 18 others showed clinical signs of COVID-19 but no antibodies against SARS-CoV-2 were detectable in their blood using an immunoprecipitation assay. Goumeniu et al. published an editorial querying the role of dogs in the Lombardy COVID-19 outbreak and recommended use of computational docking experiments to provide evidence for or against infection of dogs.43 Hence, our model data suggesting that dog ACE2 might be permissive for SARS-CoV-2 binding and infection is therefore consistent with anecdotal reports of dogs being infected with SARS-CoV-2. Hence other genetic factors could underlie the apparent lack of susceptibility of dogs to COVID-19 clinical infection.
It is known that gain of function (GOF) mutations occur in viruses that can lead to pandemics. GOF means viruses gain a new property e.g. in influenza virus GOF has been associated with the acquisition of a new function, such as mammalian transmissibility, increased virulence for humans, or evasion of existing host immunity.49 The conditioning of viruses to humans as pandemics progress is well recognized. However, the SARS-CoV-2 structures and sequences that we employed were from viruses collected very early in the pandemic. It is therefore not clear how SARS-CoV-2 could have developed such a high affinity for human ACE2, notably higher than for those of putative zoonotic sources for SARS-CoV-2, unless it has been previously selected on human ACE2 or an ACE2 of another species bearing a closely homologous spike protein binding domain. Interestingly, pangolin ACE2 bears some similarities in its SBD to human ACE2This marries with the fact that Pangolin-CoV shares a highly similar RBD to SARS-CoV-2, although their remaining sequence has only 90% similarity. This could be consistent with a process of convergent evolution whereby human and pangolin coronaviruses infecting via ACE2, have come to the same solution in respect of evolving an optimal spike RBD for binding of either human or pangolin ACE2, respectively. Our data does indicate that humans might be permissive to pangolin CoVs that use ACE2 for cell entry, a fact that needs to be borne in mind in respect of future potential coronavirus pandemic sources. However, this does not mean that pangolin ACE2 was the receptor on which the SARS-CoV-2 spike protein RBD was initially selected, with the strength of binding to pangolin ACE2 lower than binding to human ACE2. This makes it unlikely that pangolins are the missing intermediate host. If SARS-CoV-2 spike was selected on pangolin ACE2, then given the higher affinity of SARS-CoV-2 for human ACE2 than for bat ACE2, SARS-CoV-2 would have to have circulated in pangolins for a long period of time for this evolution and selection to occur and to date there is no evidence of a SARS-CoV-2 like virus circulating in pangolins.
Another possibility would be a short term evolutionary step where a pangolin was recently co- infected with a bat ancestor to SARS-CoV-2 at the same time as it was infected by a pangolin CoV allowing a recombination event to occur whereby the spike RBD of the pangolin virus was inserted into the bat CoV, thereby conferring the bat CoV with high binding for both pangolin and human

ACE2. Such recombination events are known to occur with other RNA viruses and can explain creation of some pandemic influenza strains49. Nevertheless, such events are by necessity rare as they require coinfection of the one host at exactly the same time. Most importantly, if such a recombination event had occurred in pangolins it might have been expected to have similarly triggered an epidemic spread of the new highly permissive SARS-CoV-2 like virus among pangolin populations, such as we now see occurring across the human population. Currently there is no evidence of such a pangolin SARS-CoV-2 like outbreak, making this whole scenario less likely. Indeed, pangolins might be protected from SARS-CoV-2 infection due to the existence of cross- protective spike RBD neutralising antibodies induced by exposure to pangolin CoV, given the RBD similarity of these two viruses. Another possibility which still cannot be excluded is that SARS- CoV-2 was created by a recombination event that occurred inadvertently or consciously in a laboratory handling coronaviruses, with the new virus then accidentally released into the local human population.
Given the seriousness of the ongoing SARS-CoV-2 pandemic, it is imperative that all efforts be made to identify the original source of the SARS-CoV-2 virus. In particular, it will be important to establish whether COVID-19 is due to a completely natural chance occurrence where a presumed bat virus was transmitted to humans via an intermediate animal host or whether COVID-19 has alternative origins. This information will be of paramount importance to help prevent any similar human coronavirus outbreak in the future.

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An insertion unique to SARS-CoV-2 exhibits superantigenic character strengthened by recent mutations
Market Crashes / Panic


Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized con- dition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. These symptoms and the associated laboratory values strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic superantigens to MHCII molecules and T cell receptors (TCRs). Here, we used structure-based computational models to demonstrate that the SARS-CoV-2 spike (S) exhibits a high-affinity motif for binding TCR, interacting closely with both the α- and β-chains variable domains’ complementarity-deter- mining regions. The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in any other SARS coronavirus), which is highly similar in both sequence and structure to bacterial superantigens. Further examination revealed that this interaction between the virus and human T cells is strengthened in the context of a recently reported rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2. Furthermore, the interfacial region includes se- lected residues from a motif shared between the SARS viruses from the 2003 and 2019 pandemics, which has intracellular adhesion mol- ecule (ICAM)-like character. These data suggest that the SARS-CoV-2 S may act as a superantigen to drive the development of MIS-C as well as cytokine storm in adult COVID-19 patients, with important implications for the development of therapeutic approaches.

MIS-C manifests as persistent fever and hyperinflammation with multi organ system involvement including cardiac, gastrointestinal, re- nal, hematologic, dermatologic and neurologic symptoms (5-7) which are highly reminiscent of toxic shock syndrome (TSS)

Here, we used computational modelling to determine whether the SARS-CoV-2 S possesses SAg activity. We demonstrate that an insert present in SARS-CoV-2 S, which is absent from SARS1 and MERS, me- diates high affinity, non-specific binding to the TCR. Notably, a motif of ~20 amino acids enclosing this insert unique to SARS-CoV-2 among beta coronaviruses has sequence and structure features highly similar to those of the SEB toxin. Furthermore, our analysis indicates that a SARS-CoV-2 S mutation detected in a European strain may enhance TCR binding, suggesting such mutations may account for geographical differences in MIS-C occurrence. These finding have important implications for the management and treatment of COVID-19.


SARS-CoV-2 spike harbors a high affinity site for TCR β-chain binding, which contains an insertion, P681RRA684, unique to SARS2. 

SARS-CoV-2 is distinguished by the existence of this four-residue inser- tion, PRRA, preceding the furin cleavage site (R685-S686 peptide bond) between the subunits S1 and S2 of each protomer (Fig. 2A). Structural comparison of the trimeric S proteins between SARS-CoV and SARS- CoV-2 further shows their close structural similarity in general (except for the RBD which is engaged in specific interfacial interactions (18)), but the two spikes significantly differ near the PRRARS motif unique to SARS-CoV-2, which is exposed to the extracellular medium (Fig. 2B).

Further examination of the motif near PRRA reveals close structural similarity to the SEB superantigen as well as sequence similarities to neurotoxins and a viral SAg. The insertion PRRA together with the sequentially preceding seven amino acids and succeeding Arg (fully conserved among β-coronaviruses) have been pointed out to form a motif, Y674QTQTNSPRRAR685, homologous to that of neurotoxins from Ophiophagus (cobra) and Bungarus genera, as well as neurotoxin-like regions from three RABV strains (21) (Fig. 2C). We further noticed that the same segment bears close similarity to HIV-1 glycoprotein gp120 superantigenic motif F164-V164.

Figure 2: Sequence and structural properties of the insert “PRRA” motif. A-B SARS- CoV-2 encodes both a cleavage site (1) and neurotoxin motifs (21) near the insertion PRRA that distinguishes it from SARS-CoV. (A) Sequence alignment of SARS-CoV-2 and multiple SARS-CoV and Bat SARS-like CoV strains (1) near the insertion PRRA. (B) Structural alignment of SARS-CoV-2 and SARS-CoV at the same region. The PRRARS motif is shown in red sticks. (C) Sequence similarity between neurotoxin motifs and the close neighborhood of the PRRA insert, reported earlier (21) as well as HIV-1 gp120 SAg motif (22) in the last row. (D) SARS-CoV-2 S trimer composed of S1 subu- nits only. The protomers are colored orange, red and gray, and displayed in van der Waals format. The protruding motifs E661-R685 are highlighted in white, green, red, and blue representing the hydrophobic, hydrophilic, acidic, and basic residues.


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01-MAR-2020 :: The Origin of the #CoronaVirus #COVID19
Market Crashes / Panic


What is clear is that the #COVID19 was bio-engineered.

“If they can get you asking the wrong questions, they don't have to worry about answers.”

 “There's always more to it. This is what history consists of. It is the sum total of the things they aren't telling us.”

“A paranoid is someone who knows a little of what's going on. ”

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Epic Tourism Decline Has Holiday Destinations Scrambling @economics
Tourism, Travel & Transport



Chances are you don’t have many summer vacation plans for 2020, and even if you do, they probably won’t look anything like past excursions to far-off lands.

When and where people will be able to travel again—if they feel comfortable doing so—is unclear, but countries that depend on tourism are devising strategies to welcome foreign visitors amidst the coronavirus pandemic. 

Luring guests may not be easy and providing arrangements that protect both tourists and locals will be a logistical feat.

These efforts come as the trillion-dollar international tourism industry is poised for its worst performance since 1950, according to a United Nations World Tourism Organization report. 

Tourist trips globally could drop this year 58% to 78% compared with 2019 and destinations could lose up to $1 trillion in tourism income—ending a decade of continuous growth

Figures for the first quarter of the year show that tourism is on track for the organization’s ominous scenarios, with trips down 57% in the month of March alone and a total of $80 billion in income already lost.

Saint Lucia, where income from inbound international travel represents more than half of gross domestic product, is among the first countries in the Caribbean to announce a plan to reopen. 

In the first phase, U.S. tourists will be allowed to visit the island-state beginning June 4, and 1,500 hotel rooms are being prepared to comply with a Covid-19 certification process. 

The abrupt halt of tourism in the Caribbean, where many of the island nations haven’t fully recovered from hurricanes Irma and Maria in 2017, will result in the region’s deepest recession in more than a half-century, the International Monetary Fund estimates.

Still, the GDP of their most tourism-reliant countries—Greece, Portugal, Cyprus, Malta and Croatia—is forecast to plunge between 5.8% and 9.7% in 2020.

Other popular destinations in the EU—home to nine of the 20 most-visited countries globally in 2018—want to reopen for tourists, too. Italy—among the countries in Europe hardest-hit by the virus—is lifting an unofficial border closure on June 3 for tourists from the Schengen Zone and scrapping a 14-day quarantine requirement. 

Spain is considering reopening its border to Schengen passengers in early July, while a two-week isolation for all visitors is due to end in May.

Globally, the travel and tourism sectors generated 330 million direct and indirect jobs in 2019, according to the World Travel and Tourism Council. 

However, their recent research suggests the industry is on track to lose more than 100 million jobs because of the pandemic, with 75% of them likely to come from G20 economies. 

Already 25 million jobs were lost in one month as of late April, WTTC research shows.


Airlines and hotels were the first to experience the economic impact of the pandemic. 

Scheduled flights globally plunged in April 61% compared with 2019, to 1.6 million, according to figures from OAG. 

Airlines worldwide are estimated to lose this year $314 billion in passenger revenue this year, a 55% drop compared with 2019, according to the International Air Transport Association, and as of early May airlines in Europe, the U.S. and Asia have secured more than $85 billion in state aid.

Confirmed reservations for April through September declined an average of 37% for each week of March and April compared with a year ago, according to a survey of hotels and resorts from Duetto. In recent earnings announcements, Marriott International and Hilton Worldwide both reported a 90% drop in revenue per available room in April.

Even after travelers feel comfortable booking trips again, the virus’s impact on tourism is likely to last. 

According to WTTC, the ‘new normal’ in travel will comprise additional standards and protocols in airports and hotels: tests before flying and upon arrival; contact tracing; improved hygiene and cleaning procedures on-board and during stays; and increased use of contactless check-ins and payments.



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Currency Markets at a Glance WSJ
World Currencies


Euro 1.0918

Dollar Index 99.63

Japan Yen 107.84

Swiss Franc 0.9706

Pound 1.2218

Aussie 0.6572

India Rupee 75.6825

South Korea Won 1235.21

Brazil Real 5.4435

Egypt Pound 15.86

South Africa Rand 17.5417

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@jairbolsonaro's populism is leading Brazil to disaster @FT @gideonrachman
Emerging Markets


On a visit to Brazil last year, I had a chat with a prominent financier about the parallels between Donald Trump and Jair Bolsonaro.

“They are very similar,” she said, before adding: “But Bolsonaro is much stupider.” 

But the country has the second-highest infection rate in the world and the sixth-highest recorded Covid-19 deaths. 

The number of deaths in Brazil, which accounts for roughly half the population of Latin America, is now doubling every two weeks, compared with every two months in the hard-hit UK.

Oliver Stuenkel, a professor at the Getúlio Vargas Foundation in São Paulo, says, “What Bolsonaro wants to do is to disassociate himself from the economic crisis that is approaching.”

The social isolation measures that Mr Bolsonaro decries, may actually help him politically. They could prevent the mass demonstrations that provided the impetus for the drive to impeach Ms Rousseff

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10-MAY-2020 :: ―Brazil is the global epicenter of the coronavirus.
Emerging Markets


In Brazil we have a toxic mix of a „‟Voodoo‟‟ President @jairbolsonaro and a runaway #COVID19

Brazilians aren‘t infected by anything, even when they fall into a sewer

“It‟s tragic surrealism ... I can‟t stop thinking about Gabriel García Márquez when I think about the situation Manaus is facing.” Guardian

Viruses are in essence non linear exponential and multiplicative and COVID19 has „‟escape velocity‟‟ in Brazil.

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Remittances are the largest single source of international development finance. But the World Bank projects that remittances to developing countries will slump by 23 percent this year—down to US$445 billion @CGDev
World Of Finance


Remittances are the largest single source of international development finance. But the World Bank projects that remittances to developing countries will slump by 23 percent this year—down to US$445 billion, versus the $574 billion it had projected without the crisis.

Remittances have been as large as 10 percent of gross domestic product in countries like Guatemala and Senegal, 20 percent in Honduras, and 30 percent in Haiti. 

The worst might await countries like Nepal, where the value of remittances is almost a third of GDP and prospects for migration to the Gulf—doubly slammed by falling oil prices—especially dim.

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If Brammertz did not already exist, Hollywood might have imagined him. had been known in human rights circles as something of an Indiana Jones of international justice @VanityFair
Misc.


Félicien Kabuga was one of the world’s most wanted fugitives, believed by authorities to have been responsible for underwriting the 1994 Rwandan genocide and providing the hundreds of thousands of machetes that ethnic Hutu marauders used to slaughter at least 800,000 citizens. 

But until his dramatic capture on May 16, in a dawn raid, Kabuga had been living in hiding for 26 years—in Kenya, Germany, and, recently, in France. 

Hunting génocidaires (the perpetrators of genocide) had largely become an analog business in a digital world. Investigators waited for tips from informants. 


He applied the tools of the counterterrorism trade—including cell phone geolocation, “pattern of life” intelligence, and sophisticated, big-data-crunching analytical tools—to hunting war criminals


Colonel Èric Emeraux took part in the raid. “After 26 years as a fugitive,” he said, “when you find 20 members of the gendarmerie, plus prosecutors, in your flat on a Saturday morning, you understand it is the end of the game.” 


So, the minute Kabuga was nabbed, a police technician swabbed the inside of the old man’s cheek and raced the genetic material to a forensic lab, where the DNA was compared against a 2007 sample from Germany—Kabuga’s last-known location. 

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Sub-Saharan Africa only recorded its index case on February 28 when Nigerian epidemiologists confirmed the presence of the coronavirus in an ill expatriate who had entered the country from Milan @Pol_Sec_Analyst
Africa

The first is undoubtedly timing. The United States and Italy—the two countries most affected by the coronavirus pandemic—registered their index cases on January 21 and 31 respectively.  #COVID19 

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How Mauritius beat the pandemic @mailandguardian @simonallison
Market Crashes / Panic



On March 18, a Wednesday, Prime Minister Pravind Jugnauth announced that three people in Mauritius had contracted Covid-19. 

Two cases were from a cruise ship and one was a person who had flown in from the United Kingdom. Grimly, the prime minister told the country: “We are in a state of emergency.”

Exactly eight weeks later — May 13, another Wednesday — Jugnauth’s administration made a very different announcement. 

After a total of 332 cases and 10 deaths, Mauritius was now Covid-19 free. “Mauritius now has zero active cases,” said the country’s health minister. “We have won the battle … but we have not yet won the war.”


When the scale of the pandemic became clear, the World Health Organisation (WHO) designated Mauritius as a high-risk country. Not only did the island have extensive links with hotspots in Europe and Asia — tourism is the foundation of its economy — but it is also the 10th most densely-populated country in the world. These are fertile conditions for the spread of the coronavirus.


As early as January, Mauritius had begun to restrict flights coming in from China. 

Flights from Europe were soon added to that list, and screening at airports became mandatory for all incoming passengers. Covid-19 arrived anyway.

On the day that the first three cases were confirmed, Jugnauth set up a high-level ministerial coronavirus committee. 

This was the driving force behind the country’s response, and included the ministers of health, finance, tourism, infrastructure and commerce. 

It was chaired personally by the prime minister. The committee met every day, including weekends, and sometimes meetings would go on for three hours. 

Initially the meetings were face to face — later, when one of the committee members became infected, they started meeting online.

“Having a prime minister meeting and chairing the meeting every day, it’s a commitment that I have never seen in any other country,” said Dr Laurent Musango, who sat on the committee.





“It’s the opposite to what you had in Burundi,” said Musango, referring to that country’s expulsion of the WHO’s advisory team.


Anyone identified as a contact of someone who had been infected. As of May 19 , Mauritius had conducted 92764 tests. This works out to a little over 7% of the 1.2-million population — the highest testing ratio in any African country, says the WHO.



There are several factors unique to Mauritius that made it easier to contain the virus, Caussy says. A big one is its geography: islands can shut their border in a way that mainland countries just cannot. 

Mauritius also has a small, highly-literate and largely co-operative population. It helps too that the country has a history of good governance: on the Mo Ibrahim Foundation’s African governance index, Mauritius has been ranked number one for the past decade.

But there are still plenty of things that other countries can learn from Mauritius, said Caussy. One is the importance of a free press and reliable information. 

“Freedom of expression. You have to get the public agenda. This is very important.” It means that government actions are scrutinised, and that government officials are forced to be accountable to citizens. It also means that citizens are more inclined to believe what they read in the media, and take it seriously.

Another is political will, said the WHO’s Musango. The government acted early and decisively, which allowed it to get on top of the pandemic before it got out of control. 


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The worrying development is Transmission Hotspots #COVID19 and the Spillover Moment
Africa



Kano in Nigeria for example


Western Cape growing at an alarming rate @sugan250388

Someone with close knowledge of the medical profession said it was almost impossible to secure a hospital bed in several cities.


The Aga Khan hospital in Dar es Salaam had a well-equipped ward for 80 coronavirus patients, but several were dying each night, he said.

The Question for SSA is whether these Transmission Hot Spots expand and conflate?



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02-MAR-2020 :: The #COVID19 and SSA and the R Word
Africa


We Know that the #Coronavirus is exponential, non linear and multiplicative.

what exponential disease propagation looks like in the real world. Real world exponential growth looks like nothing, nothing, nothing ... then cluster, cluster, cluster ... then BOOM!

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At a busy East African border, testing truckers created perfect conditions for coronavirus to spread @washingtonpost
Africa


NAMANGA, KENYA — When Habibu Juma Ali lined up his truck full of Whitedent toothpaste behind hundreds of others waiting to cross the border from Tanzania into Kenya, he didn’t expect to wait two weeks to get tested for the novel coronavirus.


More than 150 tested positive and were turned back. The rest spent interminable days waiting for their results.



At a meeting Friday to resolve the growing crisis, Kenya and Tanzania agreed that starting next week, drivers will have to get negative test certificates before starting their journeys. 

For many of the thousands of truckers who have already spent days or weeks in Namanga waiting for tests, that decision will have come too late.

“If my results come back positive, who can say how many people I’d have infected?” said Ali, 47. “I’m almost sure most of us here have now got the virus.”


Truck drivers distribute goods but also sometimes diseases, as became especially clear during HIV’s spread in Africa, where they carry the virus at double the rate of the general population


Tanzanian President John Magufuli has said numbers are falling, but a U.S. Embassy statement last week said that many hospitals in the former capital, Dar es Salaam, had been overwhelmed and that the likelihood of contracting the virus in that city was “extremely high.”


In Namanga, because contact tracing is done only once someone tests positive, the lag in getting results means truckers can rack up hundreds of contacts before knowing their status


Friday’s agreement stipulated that the results of all further tests of truck drivers will be released publicly but “without mentioning the nationality of the infected.”


The United States and Canada don’t test truckers crossing their 5,500-mile border. In East Africa, though, testing is more common: Uganda has found dozens of infected Kenyan truck drivers, and Zambia closed its border to Tanzanian truckers after an outbreak at the border created a hot spot there.



“Really, honestly, you are not preventing, you are spreading,” said Robert Kimani, a Kenyan driver transporting tomatoes from Iringa, in central Tanzania, who had his own reason to be angry. 

He had initially been tested five days earlier, but when results were announced, his name was missing from the list.

“There were four of us like that. They didn’t even have the courtesy to tell me what happened,” he said in an interview later. 

“In the days I’ve been waiting, where have I not been? I have been all over. Maybe the virus can be all over, too.”

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Are fund managers in the country walking on thin ice? @BD_Africa @renaldodsouza
World Of Finance


According to the data released, 52.8 percent of total Sh76.1 billion in Assets Under Management (AUM) by licensed fund managers in Kenya is invested in Kenya Government securities. This is higher than 49.8 percent and 45.8 percent in 2019 and 2018 respectively.


A significant portion of banks capital in the form of customers’ deposits is invested in Government securities. Data from the CBK shows that banks hold 54.6 percent of total domestic debt.

This is equivalent to Sh1.7 trillion of the Sh3.1 trillion domestic debt as at the end of March 2020 and over a quarter of the country’s Sh6.3 trillion public debt.


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23-DEC-2019 :: Kenyan lenders are the second most exposed to the government with almost 300 per cent of their equity lent out to the State
World Of Finance


Kenyan lenders are the second most exposed to the government with almost 300 per cent of their equity lent out to the State. However, Egyptian banks are even more exposed on lending Cairo 603 per cent of their equity.

What this tells me is that an important Source of Buy Side Demand for GOK Shilling Paper is now ''limit Long'' If You are sitting on the Credit Committee of a Kenyan Bank and exercising some degree of oversight, I would argue that then you would be demanding a Hard Cap. 

Therefore, given the fact that GOK issuance is not going to slow down but will probably accelerate, I would be keeping a close eye on the Curve. Staying ahead of the Curve was a remarkable book by the renowned Investor George Soros. It’s worth reading.

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by Aly Khan Satchu (www.rich.co.ke)
 
 
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May 2020
 
 
 
 
 
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