Study identifies genetic changes that likely enabled SARS-CoV-2 to jump from bats to humans

A new study, involving the University of Cambridge led by the Pirbright Institute, has identified important genetic changes in SARS-CoV-2 – the virus that causes COVID-19 – that may be responsible for the jump of bats to humans, and it has been determined which animals have cellular receptors that can effectively penetrate the virus into their cells.

The identified genetic adaptations were similar to those made by SARS-CoV – which caused the 2002-2003 SARS epidemic – when they were adapted from bats to infect humans. This suggests that there may be a common mechanism by which these families mutate viruses to jump from animals to humans. This concept could be used in future research to identify viruses that circulate in animals that can adapt to humans (known as zoonoses) and that could pose a pandemic threat.

‘This study used a non-infectious, safe platform to determine how changes in proteins in the cells are affected in the cells of different wild, livestock and companions, something we will need to monitor closely as additional SARS CoV-2 variants arise. the coming months, “said Dr Stephen Graham in the Department of Pathology at the University of Cambridge, who was involved in the study.

In the SARS epidemic from 2002 to 2003, scientists were able to identify closely related isolates in bats and civilians, in which the virus was thought to have been adapted to infect humans. In the current COVID-19 outbreak, however, scientists do not yet know the identity of the intermediate host or do they have similar samples to analyze. But they have the sequence of a related bat coronavirus called RaTG13, which shares 96 percent resemblance to the SARS-CoV-2 genome. The new study compared the vein proteins of both viruses and identified several important differences.

SARS-CoV-2 and other coronaviruses use their vein proteins to access cells by binding to their surface receptors, for example ACE2. Like a lock and key, the ear protein must have the right shape to match the receptors of the cell, but the receptors of each animal have a slightly different shape, meaning that the ear protein binds better to some than others.

To investigate whether these differences between SARS-CoV-2 and RaTG13 were involved in the adaptation of SARS-CoV-2 in humans, scientists swapped these regions and examined how well these resulting ear proteins bound human ACE2 receptors – using a method that does not involve the use of live virus.

The results, published in the journal PLOS Biology, showed that SARS-CoV-2 nails containing RaTG13 regions could not bind effectively to human ACE2 receptors, whereas the RaTG13 nails containing SARS-CoV-2 regions could bind more effectively to human receptors – although not at the same level as the SARS-CoV-2 areas. -CoV-2 ear protein. This possibly indicates that similar changes in the SARS-CoV-2 ear protein have historically occurred, which may have played a key role in causing the virus to jump through the species barrier.

Researchers have also investigated whether the SARS-CoV-2 ear protein can bind to the ACE2 receptors of 22 different animals to determine which of these, if any, are susceptible to infection. They showed that bat and bird receptors had the weakest interaction with SARS-CoV-2. The lack of binding to bat receptors adds weight to the evidence that SARS-CoV-2 probably adjusted its ear protein when it jumped from bats to humans, possibly via an intermediate host.

ACE2 receptors for dogs, cats and cattle have been identified as the strongest interaction with the SARS-CoV-2 ear protein. Effective access to cells can mean that infection can be more easily established in these animals, although receptor binding is only the first step in viral transmission between different animal species.

“As we saw with the outbreaks on Danish mink farms last year, it is essential to understand which animals can be infected by SARS-CoV-2 and how mutations in the viral vein protein alter their ability to infect different species,” said Graham.

The susceptibility of an animal to infection and its consequent ability to infect others depend on a variety of factors – including whether SARS-CoV-2 is capable of repeating once inside cells, and the ability of the animal to fight the virus. Further studies are needed to understand whether livestock and companion animals may be susceptible to COVID-19 infection in humans and act as reservoirs for this disease.