Popularization of research advances on COVID-19

Another coronavirus could reach humans

SARS-CoV-2, a new coronavirus identified and isolated at the beginning of 2020, has now spread throughout the world. By the 5th of March 2021, the WHO (World Health Organisation) had registered more than 114 million people infected, with 2,5 million deaths. SARS-CoV-2 seems to closely resemble the coronavirus found in bats, suspected of being a reservoir for the virus. Other coronaviruses had already emerged from this reservoir and caused epidemics in humans, such as MERS-CoV.

However, several other coronaviruses infecting bats are very close to SARS-CoV-2. Amongst them, the most similar is labelled RaTG13: 96% of its genome is identical to that of the virus responsible for COVID-19. Because of their similarities, and because of the damage caused by SARS-CoV-2, Chinese researchers (Chinese Academy of Science, Beijing), have studied the possibility that the RaTG13 virus may be able to infect humans.

To evaluate the possible passage and transmission of this virus to a new host, it is necessary to investigate whether the virus can enter this host. It is necessary therefore to study the interaction between surface proteins of the virus and the cellular receptors of different species of animal. Binding of the virus to the cellular receptor is an indispensable step for cell infection, implying successful crossing of the species barrier. In the case of SARS-CoV-2, the spike (S) surface viral protein, and more specifically its RBD, binds to the human ACE2 cellular receptor so as to enter the cell.

In order to study the interaction between the RBD of the RaTG13 virus and the human ACE2 receptor, the researchers analysed their structure. They were able to observe that the structure of the RaTG13 virus RBD, in its action of binding to the human receptor, is extremely similar to that of the RBD of SARS-CoV-2, even though the interaction seems to be 70 times weaker. In addition, they studied the binding of the RBD of RaTG13 or SARS-CoV-2 with the ACE2 receptor of 24 wild and domestic animal species (including monkeys, rabbits, mice, rats, horses, dogs and cats). The RaTG13 virus interacts with a certain number of the ACE2 receptors of these different species, although the number with which SARS-CoV-2 interacts is substantially greater. The researchers observed that the RaTG13 virus had the greatest affinity with the ACE2 receptor in horses.

The scientists also evaluated the effect of 6 mutations in the RBD of RaTG13 on its binding with the ACE2 human receptor. The 6 mutations enable entry of the virus into cells carrying the ACE2 receptor to be augmented. They also underlined the key role of position 501 of the S protein in its liaison with the ACE2 receptor. Position 501, mutated in the UK, South African and Brazilian (N501Y) variants that have now spread to many countries, had already been linked to an increase in the transmissibility of SARS-CoV-2. So just a few isolated mutations in the RBD domain could allow the RaTG13 virus to adapt to a new host. Finally, the researchers also wanted to know if infection by SARS-CoV-2 could protect against the RaTG13 virus. They therefore analysed the serum (containing antibodies) of patients who had previously been infected by SARS-CoV-2. The serum enabled the RaTG13 virus to be neutralised, thereby proving the existence of cross-immunity between the two viruses.

The RaTG13 virus may therefore be able to infect numerous different hosts: the appearance of mutations could enable it to adapt to and to spread across various animal species. This virus, like others similar to it, could also cross the species barrier and infect humans. It is therefore very important to monitor the coronaviruses carried in many animal reservoirs.

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