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N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains. | LitMetric

N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains.

Comput Struct Biotechnol J

Biomedical Research Foundation Academy of Athens, 4 Soranou Efesiou, 115 27 Athens, Greece.

Published: October 2021

AI Article Synopsis

Article Abstract

During the past two years, the world has been ravaged by a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acquired mutations in the SARS-CoV-2 genome affecting virus infectivity and/or immunogenicity have led to a number of novel strains with higher transmissibility compared to the original Wuhan strain. Mutations in the receptor binding domain (RBD) of the SARS-CoV-2 spike protein have been extensively studied in this context. However, mutations and deletions within the N-terminal domain (NTD) located adjacent to the RBD are less studied. Many of these are found within certain β sheet-linking loops, which are surprisingly long in SARS-CoV-2 in comparison to SARS-CoV and other related β coronaviruses. Here, we perform a structural and epidemiological study of novel strains carrying mutations and deletions within these loops. We identify short and long-distance interactions that stabilize the NTD loops and form a critical epitope that is essential for the recognition by a wide variety of neutralizing antibodies from convalescent plasma. Among the different mutations/deletions found in these loops, Ala 67 and Asp 80 mutations as well as His 69/Val 70 and Tyr 144 deletions have been identified in different fast-spreading strains. Similarly, deletions in amino acids 241-243 and 246-252 have been found to affect the network of NTD loops in strains with high transmissibility. Our structural findings provide insight regarding the role of these mutations/deletions in altering the epitope structure and thus affecting the immunoreactivity of the NTD region of spike protein.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489513PMC
http://dx.doi.org/10.1016/j.csbj.2021.10.004DOI Listing

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