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
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | The copyright of this article belongs to American Society for Microbiology |
| Uncontrolled Keywords: | Omicron; SARS-CoV-2; neutralizing antibodies; spike conformation; spike protein; virus entry. |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 16 Jul 2024 07:02 |
| Last Modified: | 16 Jul 2024 07:02 |
| URI: | http://crdd.osdd.net/open/id/eprint/3189 |
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