7Z0Y

THSC20.HVTR04 Fab bound to SARS-CoV-2 Receptor Binding Domain

Summary for 7Z0Y

• Entry DOI: 10.2210/pdb7z0y/pdb
• Descriptor: THSC20.HVTR04 Fab heavy chain, THSC20.HVTR04 Fab light chain, Spike protein S1, ... (6 entities in total)
• Functional Keywords: neutralizing antibody, sars-cov-2, spike, rbd, antiviral protein, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 71230.38

Authors

Wibmer, C.K. (deposition date: 2022-02-23, release date: 2022-04-13, Last modification date: 2024-11-20)

Primary citation

Hingankar, N.,Deshpande, S.,Das, P.,Rizvi, Z.A.,Wibmer, C.K.,Mashilo, P.,Ansari, M.Y.,Burns, A.,Barman, S.,Zhao, F.,Mukherjee, S.,Torres, J.L.,Chattopadhyay, S.,Mehdi, F.,Sutar, J.,Rathore, D.K.,Pargai, K.,Singh, J.,Sonar, S.,Jakhar, K.,Dandotiya, J.,Bhattacharyya, S.,Mani, S.,Samal, S.,Singh, S.,Kshetrapal, P.,Thiruvengadam, R.,Batra, G.,Medigeshi, G.,Ward, A.B.,Bhatnagar, S.,Awasthi, A.,Sok, D.,Bhattacharya, J.
A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant.
Plos Pathog., 18:e1010465-e1010465, 2022

PubMed Abstract: Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.HVTR04 and THSC20.HVTR26) showed potent neutralization of SARS-CoV-2 VOCs at picomolar concentrations, including the Delta variant (B.1.617.2). One of these (THSC20.HVTR26) also retained activity against the Omicron variant. These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein and prevent virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as a cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness.

PubMed: 35482816
DOI: 10.1371/journal.ppat.1010465

Experimental method

X-RAY DIFFRACTION (2.95 Å)