How do we know SARS-CoV-2 wasn’t man-made?
The American Association of Public Opinion Research reported that 29% of Americans polled believe that SARS-CoV-2, the virus responsible for COVID-19, was created in a lab. A group of virologists, evolutionary biologists, and pathologists published a report in the journal Nature Medicine to discuss and argue against the theory that SARS-CoV-2 was man-made. They posit the conflicting theory that SARS-CoV-2 is the product of natural selection. While this report does not contain data, it provides a series of research based arguments as to why they believe SARS-CoV-2 is the product of natural selection, passage through multiple species hosts, and adaptation to effectively spread from human to human.
The DNA sequence of SARS-CoV-2 is 96% identical to a virus found in bats, which is part of the same coronavirus family as SARS-CoV-2, SARS (Severe Acute Respiratory Syndrome), and MERS (Middle East Respiratory Syndrome). These viruses were more geographically contained but still caused deadly disease in humans in 2003 (SARS) and 2012 (MERS). However, the differences from the original bat virus are very important. One of the factors thought to increase the ability of SARS-CoV-2 to infect humans is the spike protein. The spike protein is expressed on the surface of SARS-CoV-2 and allows it to bind to host cells, so that the virus can gain entry into the cells. Think of a key and lock. Many viruses use normal processes of the host as locks to gain entry into host cells. In this case, the spike protein is the key and the lock is human angiotensin converting enzyme 2 (ACE2). ACE2 is an enzyme that binds to the outside of host cells.
The bat spike protein does not bind strongly to ACE2. Instead the parts of the SARS-CoV-2 spike protein responsible for binding are nearly identical to that region on the spike protein of a different coronavirus. This second coronavirus normally infects an endangered ant-eater like animal called the pangolin. Using the known sequence of the bat coronavirus, researchers are able to model and predict changes in the spike protein that would increase its binding to ACE2. According to the authors of this report, there are very logical changes which would increase the binding of the bat spike protein to ACE2. The substitution of the pangolin receptor binding domain is not a predicted change. The change in the spike protein of SARS-CoV-2 is most likely to have occurred through a transmission event from bats to pangolins.
Binding to ACE2 by the spike protein is further enhanced in SARS-CoV-2 by the presence of a furin cleavage site and O-linked glycans near this cleavage site. The spike protein has 2 subunits, S1 and S2. These two subunits are linked by a region, the cleavage site, that is recognized by an enzyme (in this case the enzyme is furin) which cuts the two subunits into two (cleavage in this sense is like a butcher cleaver and not revealed by a low cut top). O-linked glycans are carbohydrates which are attached by oxygen, and their presence further enhances binding of the SARS-CoV-2 spike protein to ACE2. These O-linked glycans are not found in either the bat or pangolin coronaviruses. Rather, these are found exclusively in human coronaviruses. The authors suggest that this enhancement was gained when the virus made the jump from the animal hosts to humans, and permitted this virus to be spread from human to human.
Finally, laboratory experiments which study viruses often require another type of DNA to make enough virus to carry out experiments. This is a viral backbone, because it provides a structure in which the scientist can attach the DNA sequences they want to study. There are a number of known backbones, with known sequences, which help express the DNA the researcher wants to study. There is no trace of this type of viral backbone in the sequences of SARS-CoV-2 obtained from patients. This further convinced these authors that SARS-CoV-2 was not created in the lab.
The original bat virus was probably transmitted to the pangolin. The bat virus changed to infect the pangolin and acquired the changes in the binding domain of the pangolin virus spike protein. Most likely due to illegal hunting and trade of the endangered pangolin, the virus was transmitted to humans. The pangolin spike protein modifications allowed the virus to enter cells by binding to ACE2. Finally, the addition of the O-linked glycans around the spike protein cleavage site allowed the virus to not only infect humans, but to be transmitted from human to human.
The theory that SARS-CoV-2 arose from natural selection is supported by similar cross-species transmission events that have lead to the emergence of other novel viruses. Viruses can mutate rapidly, which is why there are many cases of viruses adapting to infect new host species. These transfers have involved bat viruses (Ebola, SARS, MERS), pig viruses (swine flu), and bird viruses (avian flu). The authors of this report prove none of the theories with empirical data. Instead they compare the emerging data on SARS-CoV-2 with previous data on other coronaviruses and their own experience to critically consider the possibility that SARS-CoV-2 was engineered in a lab. It makes a compelling case that SARS-CoV-2 arose from a series of natural selection events, which could very likely occur again.
See primary paper at https://www.nature.com/articles/s41591-020-0820-9
By Daniele Cary