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Evolutionary insights into the furin cleavage sites of SARS-CoV-2 variants from humans and animals.
Nagy, Abdou; Basiouni, Shereen; Parvin, Rokshana; Hafez, Hafez M; Shehata, Awad A.
  • Nagy A; Department of Virology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Sharkia, 44511, Egypt. abdonagy@zu.edu.eg.
  • Basiouni S; Clinical Pathology Department, Faculty of Veterinary Medicine, Benha University, Benha, Egypt.
  • Parvin R; Department of Pathology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh.
  • Hafez HM; Institute of Poultry Diseases, Faculty of Veterinary Medicine, Free University, Berlin, Germany.
  • Shehata AA; Avian and Rabbit Diseases Department, Faculty of Veterinary Medicine, Sadat City University, Sadat City, Egypt. awad.shehata@vet.usc.edu.eg.
Arch Virol ; 166(9): 2541-2549, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1309045
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Polymorphism, Genetic / Furin / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: Arch Virol Year: 2021 Document Type: Article Affiliation country: S00705-021-05166-z

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Polymorphism, Genetic / Furin / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: Arch Virol Year: 2021 Document Type: Article Affiliation country: S00705-021-05166-z