Nature (not nurture) to blame for pandemic, say genome boffins

Evolution, not engineering, is to blame for Covid-19.

An analysis of the virus genome found no evidence that it was made in a laboratory or otherwise engineered.

Scientists in the US, UK and Australia, who revealed their findings in the journal Nature Medicine on Tuesday, said Covid-19 differed substantially from other coronaviruses and mostly resembled related viruses found in bats and pangolins.

The researchers, led by Kristian Andersen from the immunology and microbiology department at the Scripps Research Institute in California, referred to the new coronavirus as SARS-CoV-2.

“By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes,” said Andersen.

The first known severe illness caused by a coronavirus caused the 2003 severe acute respiratory syndrome (SARS) epidemic in China. The second began in 2012 in Saudi Arabia with the Middle East respiratory syndrome (MERS).

On December 31, Chinese authorities alerted the World Health Organisation (WHO) of an outbreak of a novel strain of coronavirus causing severe illness, which has since spread to more than 200,000 people.

Chinese scientists sequenced the genome of SARS-CoV-2 and shared it worldwide, and Andersen's team analysed the genetic template for spike proteins, armatures on the outside of the virus that it uses to grab and penetrate the outer walls of human and animal cells.

They focused on two key features of the spike protein: the receptor-binding domain (RBD), a kind of grappling hook that grips onto host cells; and the cleavage site, a molecular can opener that allows the virus to crack open and enter host cells.

The scientists found that the RBD portion of the SARS-CoV-2 spike proteins had evolved to effectively target a molecular feature on the outside of human cells called ACE2, a receptor involved in regulating blood pressure.

The spike protein was so effective at binding the human cells that the scientists concluded it was the result of natural selection, not genetic engineering.

This evidence was supported by data on SARS-CoV-2's backbone — its overall molecular structure. The scientists found that the SARS-CoV-2 backbone differed substantially from other coronaviruses and mostly resembled related viruses found in bats and pangolins.

Andersen and his collaborators then developed two possible scenarios for the new virus's most likely origins.

In the first, the virus evolved to its current pathogenic state through natural selection in a non-human host, then jumped to humans. SARS developed in civets and MERS in camels.

The researchers said SARS-CoV-2 was very similar to a bat coronavirus, but an intermediate host was probably involved between bats and humans.

In the second scenario, a non-pathogenic version of the virus jumped from an animal host into humans, then evolved to its pathogenic state.

Some coronaviruses from pangolins had an RBD structure similar to that of SARS-CoV-2, said the scientists, and a pangolin coronavirus could possibly have been transmitted to a human, either directly or through an intermediary, such as civets or ferrets.

The other distinct spike protein characteristic of SARS-CoV-2, the cleavage site, could have evolved within a human host, possibly via limited undetected circulation in the human population before the beginning of the epidemic.

The researchers said the SARS-CoV-2 cleavage site appears similar to the cleavage sites of strains of bird flu that transmit easily between people.

SARS-CoV-2 could have evolved such a virulent cleavage site in human cells and kicked off the current epidemic, as the coronavirus would possibly have become far more capable of spreading between people.

Study co-author Andrew Rambaut, from the University of Edinburgh in Scotland, said it was almost impossible to know which scenario was most likely.

If SARS-CoV-2 entered humans in its current pathogenic form from an animal source, it raised the probability of future outbreaks, as the illness-causing strain of the virus could still be circulating in the animal population and might once again jump into humans.

The chances were lower of a non-pathogenic coronavirus entering the human population, then evolving properties similar to SARS-CoV-2.