tetano
Editor, Senior Moderator
Comput Struct Biotechnol J
. 2021 Oct 4.
doi: 10.1016/j.csbj.2021.10.004. Online ahead of print.
N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains
Apostolos Klinakis[SUP] 1 [/SUP], Zoe Cournia[SUP] 1 [/SUP], Theodoros Rampias[SUP] 1 [/SUP]
Affiliations
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 of the spike protein 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.
Keywords: N-terminal domain mutations; SARS-CoV-2; immune escape; virus evolution.
. 2021 Oct 4.
doi: 10.1016/j.csbj.2021.10.004. Online ahead of print.
N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains
Apostolos Klinakis[SUP] 1 [/SUP], Zoe Cournia[SUP] 1 [/SUP], Theodoros Rampias[SUP] 1 [/SUP]
Affiliations
- PMID: 34630935
- PMCID: PMC8489513
- DOI: 10.1016/j.csbj.2021.10.004
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 of the spike protein 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.
Keywords: N-terminal domain mutations; SARS-CoV-2; immune escape; virus evolution.