TY  - JOUR
N1  - The copyright of this article belongs to American Society for Microbiology
ID  - open3189
UR  - 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
IS  - 11
A1  - Kumar, Sahil
A1  - Delipan, Rathina
A1  - Chakraborti, Debajyoti
A1  - Kanjo, Kawkab
A1  - Singh, Randhir
A1  - Singh, Nittu
A1  - Siddiqui, Samreen
A1  - Tyagi, Akansha
A1  - Jha, Vinitaa
A1  - Thakur, Krishan Gopal
A1  - Pandey, Rajesh
A1  - Vardarajan, Raghavan
A1  - Ringe, Rajesh P.
Y1  - 2023/11/30/
N2  - 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.


PB  - American Society for Microbiology
JF  - Journal of virology
VL  - 97
KW  - Omicron; SARS-CoV-2; neutralizing antibodies; spike conformation; spike protein; virus entry.
SN  - 1098-5514
TI  - Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity 
ER  -