TY - JOUR
T1 - A broadly neutralizing monoclonal antibody overcomes the mutational landscape of emerging SARS-CoV-2 variants of concern
AU - Parray, Hilal Ahmad
AU - Narayanan, Naveen
AU - Garg, Sonal
AU - Rizvi, Zaigham Abbas
AU - Shrivastava, Tripti
AU - Kushwaha, Sachin
AU - Singh, Janmejay
AU - Murugavelu, Praveenkumar
AU - Anantharaj, Anbalagan
AU - Mehdi, Farha
AU - Raj, Nisha
AU - Singh, Shivam
AU - Dandotiya, Jyotsna
AU - Lukose, Asha
AU - Jamwal, Deepti
AU - Kumar, Sandeep
AU - Chiranjivi, Adarsh K.
AU - Dhyani, Samridhi
AU - Mishra, Nitesh
AU - Kumar, Sanjeev
AU - Jakhar, Kamini
AU - Sonar, Sudipta
AU - Panchal, Anil Kumar
AU - Tripathy, Manas Ranjan
AU - Chowdhury, Shirlie Roy
AU - Ahmed, Shubbir
AU - Samal, Sweety
AU - Mani, Shailendra
AU - Bhattacharyya, Sankar
AU - Das, Supratik
AU - Sinha, Subrata
AU - Luthra, Kalpana
AU - Batra, Gaurav
AU - Sehgal, Devinder
AU - Medigeshi, Guruprasad R.
AU - Sharma, Chandresh
AU - Awasthi, Amit
AU - Garg, Pramod Kumar
AU - Nair, Deepak T.
AU - Kumar, Rajesh
N1 - Publisher Copyright:
Copyright: © 2022 Parray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85144597061&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1010994
DO - 10.1371/journal.ppat.1010994
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 36508467
AN - SCOPUS:85144597061
SN - 1553-7366
VL - 18
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 12
M1 - e1010994
ER -