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19 juin 2021 6 19 /06 /juin /2021 11:32

79 B cell epitopes were identified on the structural proteins S, M, N, the polyprotein orf1ab, and the accessory proteins orf3a, orf6, and orf8.

 

The highest ranking epitope was 1-M-24, which is found at the N-terminal end of M.

 

The patients' sera showed high magnitude reactivity between other epitopes on S, M, N and orf3a and lesser reactivity between epitopes on other proteins.

Epitopes with the highest reactivity in S were found in the fusion peptide, while less reactive epitopes were found in the receptor-binding domain.

Four of the epitopes exhibit potent neutralizing activity.
Four of the detected epitopes have previously demonstrated potent neutralizing activity, and all of them are among the top 10 epitopes in this study.

The team also found that anti-SARS-CoV-2 antibodies cross-reacted with homologous epitopes in the proteomes of other human and animal coronaviruses.

The researchers note that "hundreds of CoV [coronavirus] have been discovered in bats and other species, making contagion effects inevitable in the future."

The highest number (70) of cross-reactive epitopes was found in the bat betacoronavirus RaTG13, which is the virus most closely related to SARS-CoV-2 (96% nucleotide identity). This was followed by the pangolin coronavirus (51 epitopes) and SARS-CoV-1 (40 epitopes).

A region corresponding to the SARS-CoV-2 epitope 807-S-26 was cross-reactive in all coronaviruses, and a region corresponding to the SARS-CoV-2 epitope 1140-S-25 was cross-reactive in all betacoronaviruses.

What are the implications of the study?
The researchers say the results suggest that the structural M protein, particularly the 1-M-24 epitope, and the other new epitopes identified here should be explored as important targets in the development of improved diagnostics, vaccines and therapies for SARS-CoV- 2 and other dangerous coronaviruses that may emerge in the future.

Furthermore, “the broad cross-reactivity that we observe in some homologous peptide sequences may help guide the development of pan-CoV vaccines, especially given that antibodies that bind to 807-S-26 and 1140-S-25, the motifs of epitopes show cross-reactivity between all CoVs and all β-CoVs, respectively, are known to be potently neutralizing ”, says the team.

 

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