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What are the effects of mutations in the South African variant?

The 501Y.V2 variant of SARS-CoV-2, known as the South African variant, is now the dominant strain in South Africa and is spreading rapidly within other countries. This variant principally contains 8 mutations in the spike surface protein: L18F, D80A, D215G, K417N, E484K, N501Y and A701V, and 1 deletion of 3 amino acids, Del242-244.

Researchers in different institutes in Beijing have analysed the effects of these mutations on levels of infectivity and antibody neutralization. To this end they produced pseudo-typed or pseudo-virus viruses, that is, viral particles that are not SARS-CoV-2 particles, which do not express their own proteins on the surface but SARS-CoV-surface proteins. These pseudo-viruses are incapable of self-replicating but can enter and infect a cell one time only, by imitating the entry process of SARS-CoV-2. They are therefore incapable of self-replicating.

The scientists produced 18 types of pseudo-virus, consisting of different combinations of the 8 mutations found in the spike protein of the South-African variant, compared to the basal variant (which carries only the D614G mutation).

The researchers first of all tested the capacity of these different mutant viruses to infect cells. No significant difference was observed in the infectivity of these different mutations as compared to the basal strain. They then checked the sensitivity of these variants to monoclonal neutralizing antibodies. The majority of the monoclonal antibodies had weaker neutralization activity with the mutant viruses as compared to the basal viral strain. The researchers observed that the number of mutations in the RBD (the domain that interacts with the ACE2 cellular receptor to enable the entry of the viral particle into the cell) correlates to the aptitude of the virus to escape antibody actions. E484K and N501Y were shown to be the principal mutations responsible for this weakening of neutralization effectiveness. Position 484 corresponds to an important epitope (a region targeted by antibodies) and has been the subject of numerous mutations already described (E484A, E484G, E448D and E484K). However, the K417N mutation may cause greater sensitivity to neutralization: it could enhance the stability of an “open” conformation of the S protein, making this region more accessible to antibodies.

The results of this study show a reduction in neutralization of the South African variant by antibodies. This may be a worrying factor in relation to the effectiveness of vaccines developed against the basal strain of SARS-CoV-2. However, this study is based only on pseudotype viruses that are used as a study model and may not reflect the behaviour of a complete replicating virus.

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