To date, no one has stated the urgent universal need to aggressively investigate the true origin of SARS-CoV-2, the coronavirus responsible for COVID-19, better than Karl and Dan Sirotkin in their August 12, 2020 article “Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?”
“Despite claims from prominent scientists that SARS‐CoV‐2 indubitably emerged naturally, the etiology of this novel coronavirus remains a pressing and open question: Without knowing the true nature of a disease, it is impossible for clinicians to appropriately shape their care, for policy‐makers to correctly gauge the nature and extent of the threat, and for the public to appropriately modify their behaviour.”
As the authors correctly note, serial passage, that is, the repeated re-infection within an animal or human population allows a virus to specifically adapt to the infected species.
That process occurs naturally in the wild, but it can be greatly accelerated in the laboratory by deliberate serial passaging of viruses in cell culture systems or animals, potentially leaving few or no traces as to whether the adapted viruses are naturally-occurring or laboratory-manipulated.
That type of "gain of function" experimentation can become particularly dangerous if viruses are adapted for human infection by serial passaging them through cell cultures and animal models that have been genetically-modified to express human receptors.
There are numerous scientific publications describing serial passaging of coronaviruses through “humanised” cell cultures and animal models, thus potentially creating a new coronavirus “pre-adapted” for human infection.
At present, the scientific consensus is that SARS-CoV-2 came from bats, but how it evolved to infect humans remains unknown.
China has claimed that a bat coronavirus named RaTG13 is the closest relative to SARS-CoV-2, but RaTG13 is not actually a virus because no biological samples exist. It is only a genomic sequence of a virus for which there are now serious questions about its accuracy.
In contrast, Dr Li-Meng Yan, a Chinese virologist and whistleblower, has implied that RaTG13 may have been used to divert the world’s attention away from the true source of the COVID-19 pandemic, a novel coronavirus that originated in military laboratories overseen by China's People’s Liberation Army and created by the manipulation of Zhoushan coronaviruses ZC45 and/or ZXC21.
SARS-CoV-2 has signs of serial passaging and the direct genetic insertion of novel amino acids sequences for which no natural evolutionary pathway has been identified.
Although SARS-CoV-2 appears to have the “backbone” of bat coronaviruses, its spike protein, which is responsible for binding to the human cell and its membrane fusion-driven entry, has sections that do not appear in any closely-related bat coronaviruses.
SARS-CoV-2’s receptor binding domain, the specific element that binds to the human cell, has a ten times greater binding affinity than the first SARS virus that caused the 2002-2003 pandemic.
Furthermore, SARS-CoV-2 appears to be “pre-adapted” for human infection and has not undergone a similar natural mutation process within the human population that was observed during the 2002-2003 SARS outbreak.
Those observations plus the inexplicable genetic distance between SARS-CoV-2 and any of its potential bat predecessors suggest an accelerated evolutionary process obtained by laboratory-based serial passaging through genetically-engineered mouse models containing humanised receptors previously developed by China.
The other unique feature of SARS-CoV-2 is a furin polybasic cleavage site that facilitates membrane fusion between the virus and the human cell and widely known for its ability to enhance pathogenicity and transmissibility, but also is not present in any closely related bat coronaviruses.
There are no readily-available animal models to produce a unique furin polybasic cleavage site by serial passaging, but techniques for the artificial insertion of such furin polybasic cleavage sites by genetic engineering have been used for over ten years.
To paraphrase Karl and Dan Sirotkin, unless the zoonotic hosts necessary for completing a natural jump from animals to humans are identified, the dual‐use gain‐of‐function research practice of viral serial passage and the artificial insertion of unique viral features should be considered viable routes by which SARS-CoV-2 arose and the COVID-19 pandemic was initiated.
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Lawrence Sellin, PhD is a retired US Army Reserve colonel. He has previously worked at the US Army Medical Research Institute of Infectious Diseases and conducted basic and clinical research in the pharmaceutical industry.