SARS-CoV-2 was not made in a laboratory, researchers say

The novel coronavirus that causes COVID-19 mostly likely has a natural origin. It does not appear to be created in a laboratory, according to a new study published in Nature Medicine on March 17.

This is the seventh coronavirus that researchers have found that can infect humans. It is one of three that causes severe illness or death. The research team of Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes, and Robert F. Garry examined the virus’ genome by comparison of different coronaviruses to discover two notable features.

Feature one is that SARS-CoV-2 seems to be optimized to bind to ACE2 but not in the way that was proposed to be optimal for SARS-CoV the coronavirus that caused the SARS outbreak in 2003. Optimizing ACE2 binding based on prior knowledge of SARS-CoV would have been a probable laboratory manipulation. Because SARS-CoV-2 does not have a predicted optimized binding sequence, it is unlikely that SARS-CoV-2 is the result of a laboratory manipulation.

The second notable feature is a polybasic cleavage site at the boundary of two of the spike protein’s subunits. Cleavage sites affect host range and infectivity. Polybasic cleavage sites have been observed in other human coronaviruses but not in SARS-CoV-2’s closest relatives. Scientists anticipate that close relatives of SARS-CoV-2 with this same polybasic cleavage site will soon be discovered in an animal host.

Theories of transmission explored in this study include (i) natural selection in an animal before zoonotic transfer and (ii) natural selection in humans following zoonotic transfer. 

Initial cases of COVID-19 were linked to the Huanan market in Wuhan. There were many animals in that market including bats and illegally imported Malayan pangolins which carry coronaviruses with the SARS-CoV-2 optimized binding sequence. Since the sampling of animal coronaviruses is far from complete the direct progenitor to SARS-CoV-2 has not been identified. If SARS-CoV-2 acquired both notable features before jumping into humans the authors postulate that the animal host would require a sizable population and an ACE2 gene similar to the human one.

A second theory is that a virus similar to SARS-CoV-2 jumped into humans but passed undetected by human-to-human transmission until it acquired adaptations that enable the severity of disease observed with COVID-19. The scenario assumes that there was a period of unrecognized transmission prior to late November 2019. 

Understanding how the SARS-CoV-2 virus jumped species boundaries will give key insights that could show whether or not re-emergence could happen. For example if natural selection occurred before transfer to humans it is possible that the animal reservoir could once more re-infect humans.