Publikationsdatenbank

Evolutionary insights into the furin cleavage sites of SARS-CoV-2 variants from humans and animals (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Nagy, Abdou

Basiouni, Shereen

Parvin, Rokshana

Hafez, Hafez M. (WE 15)

Shehata, Awad A.

Quelle

Archives of virology : official journal of the Virology Division of the International Union of Microbiological Societies

Bandzählung: 166

Heftzählung: 9

Seiten: 2541 – 2549

ISSN: 0304-8608

Sprache

Englisch

Verweise

URL (Volltext): https://link.springer.com/article/10.1007/s00705-021-05166-z

DOI: 10.1007/s00705-021-05166-z

Pubmed: 34258664

Kontakt

Nutztierklinik: Abteilung Geflügel

Königsweg 63
14163 Berlin
+49 30 838 62676
gefluegelkrankheiten@vetmed.fu-berlin.de

Abstract / Zusammenfassung

The SARS-CoV-2 spike protein Q677P/H mutation and furin cleavage site (FCS) have been shown to affect cell tropism and virus transmissibility. Here, we analyzed the frequency of Q677P/H and FCS point mutations in 1,144,793 human and 1042 animal spike protein sequences and from those of the emergent variants B.1.1.7, B.1.351, P.1, B.1.429 + B.1.427, and B.1.525, which were deposited in the database of the GISAID Initiative. Different genetic polymorphisms, particularly P681H and A688V, were detected in the FCS, mainly in human isolates, and otherwise, only pangolin and bat sequences had these mutations. Multiple FCS amino acid deletions such as Δ680SPRRA684 and Δ685RSVA688 were only detected in eight and four human isolates, respectively. Surprisingly, deletion of the entire FCS motif as Δ680SPRRARSVA688 and Δ680SPRRARSVAS689 was detected only in three human isolates. On the other hand, analysis of FCS from emergent variants showed no deletions in the FCS except for spike P681del, which was detected in seven B.1.1.7 isolates from the USA. Spike Q677P was detected only once in variant, B.1.1.7, whereas Q677H was detected in all variants, i.e., B.1.1.7 (n = 1938), B.1.351 (n = 28), P.1 (n = 9), B.1.429 + B.1.427 (n = 132), and B.1.525 (n = 1584). Structural modeling predicted that mutations or deletions at or near the FCS significantly alter the cleavage loop structure and would presumably affect furin binding. Taken together, our results show that Q677H and FCS point mutations are prevalent and may have various biological effects on the circulating variants. Therefore, we recommend urgent monitoring and surveillance of the investigated mutations, as well as laboratory assessment of their pathogenicity and transmissibility.