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The D614G mutation makes the virus more infectious

The SARS-CoV-2 virus emerged in Wuhan in China at the end of 2020 and rapidly spread worldwide. The entry of the viral particle into the cell depends upon the interaction of the spike (S) surface viral protein, or more specifically the RBD (“Receptor Binding Domain”), with the ACE2 cellular receptor. During the pandemic a variant with the D614G mutation rapidly became the dominant strain.

This mutation, situated within the S protein and outside the RBD domain, causes a change in the protein’s conformation and increases its capacity for binding with the ACE2 receptor. Researchers at the University of Berne in Switzerland have recently shown that this mutation gives the variant a selective advantage, increasing its capacities for replication and transmission.

The researchers firstly analysed in vitro the effects of the D614G mutation on the binding of the S protein of the virus to the ACE2 cellular receptor. They then studied capacities for replication of the original (614D) virus and the variant (614G) in human nasal and bronchial epithelial cells. It emerged that viral replication is increased in the variant carrying the 614G mutation.

After these in vitro tests the scientists carried out in vivo tests on different animal models: mice, hamsters and ferrets. In mice expressing human ACE2 cellular receptors, they firstly showed that replication capacity in the 614G variant is greater than in that of the original virus. In hamsters, a good model for illness caused by SARS-CoV-2 in humans, it was observed that transmission of the 614G variant is increased in comparison with the original virus. However, the variant did not have any impact on the seriousness of the illness. Finally, the researchers confirmed the same results with ferrets as they had obtained with the hamsters.

This can be schematically represented as follows:

In conclusion, the D614G mutation provides the virus with increased affinity for the ACE2 cellular receptor, an increase in rates of viral replication and more efficient transmission of the virus in different model animals. Other variants may appear, whether in humans or in the animal reservoir, as was the case with mink farms. It is therefore important to study emerging variants in vitro and in vivo so as to anticipate possible increases in transmission capacity or in viral virulence.

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