There are new indications that China manufactured the novel coronavirus.
The unique structural features of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, produce an extremely high infection rate and multi-organ secondary infections making this virus more dangerous and challenging for therapeutic interventions.
Although sharing the same human angiotensin converting enzyme-2 receptor, SARS-CoV-2 is more selective for the human receptor and is, overall, far more infectious than SARS-CoV-1, the coronavirus responsible for the 2002-2003 pandemic, which also originated in China.
One of those unique features of SARS-CoV-2 is a furin polybasic cleavage site that facilitates membrane fusion between the virus and the human cell and is widely known for its ability to enhance pathogenicity and transmissibility, but is not present in any closely related bat coronaviruses.
The enhanced ability for membrane fusion may be a cause for the multi-organ infection observed in SARS-CoV-2 patients.
A new scientific study published on August 19, 2020 suggests that other structures in SARS-CoV-2, similar to those found in Middle East Respiratory Syndrome coronavirus (MERS-CoV), may also contribute to that alternate infection process.
The MERS-CoV 2012 pandemic produced a total of 2519 cases and 866 deaths, an extraordinary 34% mortality rate.
Like SARS-CoV-2, MERS-CoV is believed to have originated in bats of the beta-coronavirus lineage, but may have passed through camels as an intermediate host before infecting humans.
Unlike SARS-CoV-2, which uses the angiotensin converting enzyme-2 receptor for human infection, MERS-CoV uses a different receptor, Dipeptidyl peptidase 4 (DPP4), and its overall structure is only 40% similar SARS-CoV-2, meaning one could not have evolved from the other.
Yet, SARS-CoV-2 appears to possess a dual receptor strategy for the infection of human cells, similar to MERS-CoV.
In a comparative sequence analysis of the N-terminal domain of the spike protein that drives the binding and fusion process, the authors identified three extended “loop” regions in SARS-CoV-2 and MERS-CoV, but not in SARS-CoV-1, which may give SARS-CoV-2 additional capability to bind to and enter a variety of human cells.
Taken together the unique structural features of SARS-CoV-2 suggest a coronavirus that was highly adapted for human infection.
Over the course of the COVID-19 pandemic, numerous unsuccessful attempts have been made to provide conclusive evidence that SARS-CoV-2 is naturally occurring.
A recent non-peer reviewed article “A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic,” written by Jonathan Latham and Allison Wilson and published on their own website has garnered some interest in the non-scientific media as a possible explanation for the natural origin of SARS-CoV-2.
This elegantly-written and well-documented review, which provides a unique and valuable translation of a Chinese clinical study, is nevertheless marred by offering an untenable theory of the origin of SARS-CoV-2 based on the serendipitous linking of a series of undocumented assumptions.
Although not concisely stated, the Latham-Wilson theory seems to suggest that SARS-CoV-2 originated as respiratory infections in miners working in a cave in Mojiang, Yunnan Province China in 2012, who were infected by a coronavirus while working among bat feces, presumably by RaTG13, SARS-CoV-2's alleged closest relative,
Over time, RaTG13 rapidly evolved inside at least one of the miners to create SARS-CoV-2. Biological samples from that miner eventually found their way to the Wuhan Institute of Virology, where unfrozen samples of the fully human-adapted SARS-CoV-2 infected a laboratory worker and began the COVID-19 pandemic.
First of all, the extent of viral evolution in a single patient that would be required to go from RaTG13 to SARS-CoV-2, about 1,200 nucleotides, is unprecedented in the annals of scientific inquiry.
Latham and Wilson attribute the adaptation to the viral load within a large lung surface area and, in particular, a lengthy infection lasting over four months.
Yet, despite the presence of an active infection of a coronavirus highly adapted for human infection, there is no evidence of human-to-human transmission, even though the Chinese clinical study provides no indication of special quarantine efforts and a therapeutic regime resembling that for ordinary respiratory infections, including fungal infections.
Although it seems likely that the miners experienced an initial viral respiratory infection and secondary, probably bacterial infections, tests for viral infections, including SARS-CoV-1, were negative during the course of hospitalisation.
It was only afterwards, that the Chinese clinical study mentions a positive test for an unidentified virus, one possibility being henipa-like virus, which was also discovered in the same cave along with numerous types of bat coronaviruses.
Strangely, the Wuhan Institute of Virology was experimenting with RaTG13 during 2017 and 2018, while SARS-CoV-2 was supposedly tucked away in a freezer, the Chinese scientists never making the connection between RaTG13 and the miners' infection.
Finally, although not conclusive in itself, it seems that such a unique, direct bat-to-human natural coronavirus infection would have been big news in the virology community in 2012, yet it went practically unnoticed.
If the Latham and Wilson theory proves anything, it demonstrates the lengths one must go in evidence-stretching to show that SARS-CoV-2 is naturally-occurring, when one begins by precluding the possibility that it was manufactured in a laboratory.
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. His email address is firstname.lastname@example.org.
(Disclaimer: The opinions expressed above are the personal views of the author and do not reflect the views of ZMCL.)