New studies clearly indicate that the human COVID-19 causing virus, SARS-CoV-2, developed the ability to infect humans in bats.

There has been a significant debate about the origin of SARS-CoV-2 virus. A major concern was that it was “engineered by humans as a bioterrorism weapon.” Recent data, however, show that this virus probably developed the ability to infect humans while infecting bats and other species prior to jumping to humans. 

Several scientific groups examined the genetic sequence of coronaviruses isolated from bats and pangolins in different areas of Asia. What they found is a remarkable evolution of these viruses that eventually yielded a virus that could readily infect human beings.

The spike protein on the virus (red arms) binds to the ACE2 protein on respiratory cells to initiate COVID-19 infection.

One analysis focused on the gene sequence of the virus’ spike protein, which is the protein that binds to the ACE2 protein on humans cells and allows infection of cells lining the respiratory tract. When examining the spike protein sequence from different bats and pangolins in Asia, it becomes clear there were changes in the genetic sequence that markedly altered the ability of these viruses to infect different species. 

These viruses essentially split into two groups — one group that infected through the ACE2 protein (like SARS-CoV-2) and another group that appears to infect through another mechanism. This latter group of viruses, isolated initially from Cambodian bats, has a unique mutation in this region that prevents any binding to any ACE2 protein and likely causes no infection in humans. 

The ACE2 binding protein regions of the spike protein (Identified as RBD) are similar between SAR-CoV-2 and the Bat RaTG13 and GD pangolin viruses. This suggests these mutations first occurred in other animals.

In the ACE2 binding group of viruses there is evidence that these viruses evolved in several species of animals, and can infect may different animals. This indicates these viruses can bind to ACE2 proteins from many species. The fact that even SARS-CoV-2 binds efficiently to the ACE2 protein of several animal species would seem to invalidate concerns that the SARS-CoV-2 was purposely either selected or specifically optimized for human ACE2 binding.

Bat, pangolin and human viruses bind to the human ACE2 protein. Therefore the bat and pangolin viruses can infect humans. In fact, the pangolin virus (orange line) binds to human cells better than SARS-CoV-2 (purple line)!

Unfortunately, this also suggests that that the human ACE2 binding of SARS-CoV-2 is not entirely optimized for the human ACE2 protein binding. This suggests that new variants could become better at infecting humans through adaptive evolution as the virus spreads through the human population   

While this information resolves the engineering concerns, it raises concerns about new mutations that can improve human infectivity. Despite this, the more we know about this virus the better we will be at understanding how to defeat it as new variants arise.

Published by jbakerjrblog

Immunologist, former Army MD, former head of allergy and clinical immunology at University of Michigan, vaccine developer and opinionated guy.

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