Record Details

Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity

DIR@IMTECH: CSIR-Institute of Microbial Technology

View Archive Info
 
 
Field Value
 
Title Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity
 
Creator Kumar, Sahil
Delipan, Rathina
Chakraborti, Debajyoti
Kanjo, Kawkab
Singh, Randhir
Singh, Nittu
Siddiqui, Samreen
Tyagi, Akansha
Jha, Vinitaa
Thakur, Krishan Gopal
Pandey, Rajesh
Vardarajan, Raghavan
Ringe, Rajesh P.
 
Subject QR Microbiology
 
Description The Omicron subvariants have substantially evaded host-neutralizing antibodies and adopted an endosomal route of entry. The virus has acquired several mutations in the receptor binding domain and N-terminal domain of S1 subunit, but remarkably, also incorporated mutations in S2 which are fixed in Omicron sub-lineage. Here, we found that the mutations in the S2 subunit affect the structural and biological properties such as neutralization escape, entry route, fusogenicity, and protease requirement. In vivo, these mutations may have significant roles in tropism and replication. A detailed understanding of the effects of S2 mutations on Spike function, immune evasion, and viral entry would inform the vaccine design, as well as therapeutic interventions aiming to block the essential proteases for virus entry. Thus, our study has identified the crucial role of S2 mutations in stabilizing the Omicron spike and modulating neutralization resistance to antibodies targeting the S1 subunit.

The Omicron subvariants have substantially evaded host-neutralizing antibodies and adopted an endosomal route of entry. The virus has acquired several mutations in the receptor binding domain and N-terminal domain of S1 subunit, but remarkably, also incorporated mutations in S2 which are fixed in Omicron sub-lineage. Here, we found that the mutations in the S2 subunit affect the structural and biological properties such as neutralization escape, entry route, fusogenicity, and protease requirement. In vivo, these mutations may have significant roles in tropism and replication. A detailed understanding of the effects of S2 mutations on Spike function, immune evasion, and viral entry would inform the vaccine design, as well as therapeutic interventions aiming to block the essential proteases for virus entry. Thus, our study has identified the crucial role of S2 mutations in stabilizing the Omicron spike and modulating neutralization resistance to antibodies targeting the S1 subunit.
 
Publisher American Society for Microbiology
 
Date 2023-11-30
 
Type Article
PeerReviewed
 
Relation https://journals.asm.org/doi/full/10.1128/jvi.00922-23?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
http://crdd.osdd.net/open/3189/
 
Identifier Kumar, Sahil and Delipan, Rathina and Chakraborti, Debajyoti and Kanjo, Kawkab and Singh, Randhir and Singh, Nittu and Siddiqui, Samreen and Tyagi, Akansha and Jha, Vinitaa and Thakur, Krishan Gopal and Pandey, Rajesh and Vardarajan, Raghavan and Ringe, Rajesh P. (2023) Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity. Journal of virology, 97 (11). ISSN 1098-5514