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A broadly neutralizing monoclonal antibody overcomes the mutational landscape of emerging SARS-CoV-2 variants of concern.
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.
  • Parray HA; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Narayanan N; Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Garg S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Rizvi ZA; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Shrivastava T; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Kushwaha S; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
  • Singh J; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Murugavelu P; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Anantharaj A; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Mehdi F; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Raj N; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Singh S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Dandotiya J; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Lukose A; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Jamwal D; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Kumar S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Chiranjivi AK; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Dhyani S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Mishra N; Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
  • Kumar S; ICGEB-Emory Vaccine Center, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
  • Jakhar K; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Sonar S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Panchal AK; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Tripathy MR; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Chowdhury SR; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Ahmed S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Samal S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Mani S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Bhattacharyya S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Das S; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Sinha S; Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
  • Luthra K; Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
  • Batra G; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Sehgal D; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
  • Medigeshi GR; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Sharma C; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Awasthi A; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Garg PK; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Nair DT; Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, Haryana, India.
  • Kumar R; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
PLoS Pathog ; 18(12): e1010994, 2022 12.
Article in English | MEDLINE | ID: covidwho-2162605
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 FabRBD 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Animals / Humans Language: English Journal: PLoS Pathog Year: 2022 Document Type: Article Affiliation country: Journal.ppat.1010994

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Animals / Humans Language: English Journal: PLoS Pathog Year: 2022 Document Type: Article Affiliation country: Journal.ppat.1010994