Host-virus interaction drives adaptive mutation in bat CoV related to SARS-CoVs.

Origin of SARS-CoV in Bats

The earlier SARS outbreak in China was the result of a virus almost entirely identical to that in market civets in the Chinese province of Guangdong. Following this, many other similar CoVs, called SARS-related (SARSr) CoVs, have been found all over China and Europe, in horseshoe bats, sharing 96% of nucleotides with both human and civet SARS-CoVs.

The greatest consistent variability was in the spike protein-encoding region and the accessory protein ORF3, and 8. Every single nucleotide in the SARS-CoV has been found in one or other bat CoV genome. This indicates that the SARS-CoV could well have arisen in bats through recombination.

It is essential to find the key sites on the virus, which play a crucial part in the ability to jump species since these could predict the odds of such events occurring between animals and humans. The researchers have already discovered a variety of SARSr-CoV viruses that can infect Chinese horseshoe bats, which have significant genetic diversity. The current study focuses on a single element, namely, the ACE2 molecule in the bat host.

Multiple ACE2 Receptors and Spike Proteins

There is a range of ACE2 molecules which can support infection with either SARS or SARSr CoVs, but the degree of readiness with which they bind to the variety of spike proteins found in the different viruses varies. Among them, the SARSr-CoV has a higher binding affinity to the human ACE2 molecule, which could indicate the high possibility of species spillover to humans.

The presence of certain specific residues at the receptor-SARSr-CoV spike protein junction suggests that such adaptation has been going on for a considerable period of time. This indicates the need to keep watch for a potential zoonotic pandemic, not unlike the current SARS-CoV outbreak.

These viruses consist of two clades distinguished by the size of the S protein. The variations in the receptor-binding domain (RBD) do not hinder the binding of ACE2 by any clade 1 strain, but those in clade 2 cannot because of deletions. This narrows down the field of origin of SARS-CoV.