Author:
Parray Hilal Ahmad,Narayanan Naveen,Garg Sonal,Rizvi Zaigham Abbas,Shrivastava Tripti,Kushwaha Sachin,Singh Janmejay,Murugavelu Praveenkumar,Anantharaj Anbalagan,Mehdi Farha,Raj Nisha,Singh Shivam,Dandotiya Jyotsna,Lukose Asha,Jamwal Deepti,Kumar Sandeep,Chiranjivi Adarsh K.,Dhyani Samridhi,Mishra Nitesh,Kumar Sanjeev,Jakhar Kamini,Sonar Sudipta,Panchal Anil Kumar,Tripathy Manas Ranjan,Chowdhury Shirlie Roy,Ahmed Shubbir,Samal Sweety,Mani Shailendra,Bhattacharyya Sankar,Das Supratik,Sinha Subrata,Luthra Kalpana,Batra Gaurav,Sehgal Devinder,Medigeshi Guruprasad R.,Sharma Chandresh,Awasthi Amit,Garg Pramod Kumar,Nair Deepak T.,Kumar Rajesh
Abstract
The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.
Funder
THSTI Intramural grant
Bill and Melinda Gates Foundation
Regional Centre for Biotechnology
Ministry of Science and Technology, Government of India
ESRF Access Program of the Department of Biotechnology
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
Reference47 articles.
1. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies;Y Cao;Nature,2021
2. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies;LA VanBlargan;Nat Med,2022
3. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor;Nature,2020
4. Extremely potent monoclonal antibodies neutralize Omicron and other SARS-CoV-2 variants;Z Chen;medRxiv,2022
5. Predicting the mutational drivers of future SARS-CoV-2 variants of concern;MC Maher;Sci Transl Med,2022