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SARS-CoV-2 Virus−Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response

Luís Queirós-Reis, Priscilla Gomes da Silva, José Gonçalves, Andrea Brancale, Marcella Bassetto Orcid Logo, João R. Mesquita

International Journal of Molecular Sciences, Volume: 22, Issue: 19, Start page: 10836

Swansea University Author: Marcella Bassetto Orcid Logo

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DOI (Published version): 10.3390/ijms221910836

Abstract

Coronavirus disease 19, or COVID-19, is an infection associated with an unprecedented worldwide pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has led to more than 215 million infected people and more than 4.5 million deaths worldwide. SARS-CoV-2 cell infe...

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Published in: International Journal of Molecular Sciences
ISSN: 1422-0067
Published: MDPI AG 2021
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa58363
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Abstract: Coronavirus disease 19, or COVID-19, is an infection associated with an unprecedented worldwide pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has led to more than 215 million infected people and more than 4.5 million deaths worldwide. SARS-CoV-2 cell infection is initiated by a densely glycosylated spike (S) protein, a fusion protein, binding human angiotensin converting enzyme 2 (hACE2), that acts as the functional receptor through the receptor binding domain (RBD). In this article, the interaction of hACE2 with the RBD and how fusion is initiated after recognition are explored, as well as how mutations influence infectivity and immune response. Thus, we focused on all structures available in the Protein Data Bank for the interaction between SARS-CoV-2 S protein and hACE2. Specifically, the Delta variant carries particular mutations associated with increased viral fitness through decreased antibody binding, increased RBD affinity and altered protein dynamics. Combining both existing mutations and mutagenesis studies, new potential SARS-CoV-2 variants, harboring advantageous S protein mutations, may be predicted. These include mutations S13I and W152C, decreasing antibody binding, N460K, increasing RDB affinity, or Q498R, positively affecting both properties.
Keywords: SARS-CoV-2; Spike protein; hACE2; protein structures
College: College of Science
Funders: No funding
Issue: 19
Start Page: 10836