this paper is crucial to designing a virus that is infective in humans--molecular geneticist

5-1-20  The Newsweek report revealed an alarming tidbit: The Wuhan lab at the center of the controversy had for years been engaged in gain-of-function research.  What exactly is it?  It’s a line of research where scientists take viruses and study how they might be modified to become deadlier or more transmissible. https://webcache.googleusercontent.com/search?q=cache:RMzskv7jhwsJ:https://triblive.com/news/politics-election/trump-administration-ended-pandemic-early-warning-program-to-detect-coronaviruses/+&cd=28&hl=en&ct=clnk&gl=us&client=safari

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12-1-2014   These critical genetic features include those that based on previous experimental validation are predicted to confer virulence and/or have the ability to transmit efficiently in mammals.  In this context, genomes are sequenced, mutations are detected relative to earlier viruses and prototype strains, significance is appraised based on prior knowledge of genetic markers, and phenotypes are tested using a variety of in vitro and in vivo experiments. Viruses possessing phenotypes of interest or concern often become candidates for reverse-genetics studies, which are essential to elucidate the precise molecular correlate(s) of a given phenotype.  https://mbio.asm.org/content/5/6/e02431-14

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2013    Now for the first time since the controversy erupted in November 2011, there is a growing recognition among scientists that GOF virology – experiments with H5N1 and now H7N9 and H7N7 viruses – will not help us predict a pandemic  (Morse et al, 2012; Merson et al, 2013), nor will it help us develop more effective vaccines (Butler, 2012; Malakoff, 2013), the two principal arguments for doing the research.   https://www.embopress.org/doi/pdf/10.1002/emmm.201303475   

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  The purported benign aim of this line of research was to investigate the potential of bat coronaviruses to infect humans, to improve scientists’ ability to predict pandemics, and to develop vaccines or other therapies. However, this is also gain-of-function research, which aims to make viruses more infective or transmissible.  Such research has come under increasing criticism by scientists for many years, due to its tendency to pose huge risks for little benefit….The NIH’s money was directed through the US-based Eco-Health Alliance, headed by Dr Peter Daszak,  USAID and Chinese institutions….

  In the experiment at WIV, China 2014-5 the scientists took a mouse coronavirus and exchanged its spike  protein – the part on the surface of the virus that determines infectivity – for one from a bat coronavirus that was similar to the virus that causes the human epidemic disease SARS. They kept the mouse virus “backbone” – its basic RNA and protein molecular structure. The bat coronavirus, in its natural state, was unable to infect humans as its spike protein was inadequate – it was not able to dock onto the ACE2 receptor on human cells. 

  Infectivity is supposed to be determined just by the spike protein.  So joining the bat spike protein with the mouse virus backbone should have resulted in a virus that was non-infectious to humans.  But the resulting genetically engineered chimeric virus unexpectedly turned out to be highly infectious to humans….

  The London-based molecular geneticist

Dr. Michael Antoniou commented, “The information on amino acid sequences provided in this paper is crucial to designing a virus that is infective in humans.  Anyone with access to a standard laboratory would be able to use the information to estimate the amino acid sequence needed to engineer an RBD that would be highly likely to infect human cells.”

  Dr. Antoniou explained how their data makes what would otherwise have been a laborious process far quicker and more efficient.  If you start with no information, you could engineer a human-infective virus like SARS-CoV-2 by using a “directed iterative evolutionary selection process”. This would involve using genetic engineering in a mutagenesis procedure to generate a large number of randomly mutated versions of the SARS-CoV spike protein RBD, which would then be selected for strong binding to the human ACE2 receptor and consequently high infectivity of human cells.

  In 2017 WIV scientists, including Shi Zhengli, published a study with funding shared between Chinese and US institutions, the latter including the US NIH and USAID, found that two genetically engineered chimeric viruses replicated “efficiently” in human cells.  The consequences of escape of such viruses could be serious….

  After all, if the belief gained traction that the virus might have escaped from a lab, virologists could expect their research to be “impacted adversely by tighter laboratory controls”, as the leading vaccine researcher Professor Nikolai Petrovsky has pointed out in explaining why the majority of scientists seem to be supporting the idea that the virus originated in a wet market rather than a lab.     https://www.gmwatch.org/en/news/latest-news/19410-chinese-and-us-scientists-genetically-engineered-bat-coronaviruses-in-dangerous-gain-of-function-research-stretching-back-years