BENGALURU: As the spread of SARS-CoV-2 continues to add to the global Covid-19 cases tally, a group of Indo-US scientists that analysed DNA data from more than 3 lakh individuals have found that the virus can be fooled by introducing variants of the receptor in the human body as decoys Scientists from MedGenome and SciGenom Research Foundation (SGRF), who collaborated to analyse DNA sequence and variation data from more than 3 lakh individuals to predict susceptibility to the Covid-19 disease, identified variations in the ACE-2 protein gene (in humans) that are predicted to make individuals more susceptible to the virus.While the study started off with the need to understand why some individuals are more severely affected than others by the virus, important for managing at-risk individuals — it also found how the virus could be countered. The pre-print study has been published in bioRxiv, an open access preprint repository for the biological sciences.Beating Virus At Its GameSekar Seshagiri, president, SciGenom Research Foundation, and lead author of the paper told TOI over telephone from the US: “The virus is a submicroscopic tennis ball with little spikes (S-protein) jetting out of its surface. In the middle of the ball is the viral genome. The virus uses its S-protein to attach to a human host cell receptor called ACE2 and sneaks into the cell. ACE2 has a normal cellular role in managing blood pressure in our body. It sticks out of the cell like an antenna from the cell surface.”The virus cleverly attaches to the ACE2 and uses it like a door to get into the cell. Once inside the cell it co-opts and takes control of the cellular machinery to make tens of thousands of copies of itself and eventually gets out to infect other neighbouring cells.As this process continues there is so much of the virus in the infected person’s lungs, that the body expels it by way of coughing and sneezing. The virus hitches a ride when the patient coughs or sneezes and travels in expelled body fluid droplets. If it finds a new human host it settles down, takes over the next victim and thus spreads.Therefore, Seshagiri said that a modified ACE2 carrying the more sticky variants can be made recombinantly like insulin in cell culture. “The purified ACE2 — “modified antenna” — can be given to patients with perhaps serious symptoms as a treatment. It will act like a sink, absorb the virus and prevent it from sticking to ACE2 on the cells and invading it. It’s a way to beat the virus in its own game by supplying a rationally engineered ‘decoy ACE2’ variant,” he said.ACE-2 & SusceptibilitySARS-CoV-2 enters human cells by binding to ACE2, a cell surface protein. One of the reasons the virus is highly infectious is because it can bind to the ACE2 cell receptor with higher affinity compared to the previous SARS-CoV virus which caused SARS, which was less contagious even though it caused an epidemic in 2003.Natural human ACE2 protein variation encoded in an individual’s DNA can allow the virus to bind to ACE2 either strongly or weakly and hence alter their susceptibility to the disease which has caused the current pandemic.“We analyzed ACE2 protein altering variants from over 3 lakh individuals variant data from across the world and have found variants that are predicted to bind to the virus less tightly and hence make individuals less susceptible – giving these individuals natural protection against the invading virus,” Seshagiri said.“The converse is also true; in this data set, we found ACE2 variants that will render individuals more susceptible to the virus,” Dr Eric Stawiski, vice-president, Bioinformatics, MedGenome said.