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TitleA combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant.
Journal, issue, pagesPLoS Pathog, Vol. 18, Issue 4, Page e1010465, Year 2022
Publish dateApr 28, 2022
AuthorsNitin Hingankar / Suprit Deshpande / Payel Das / Zaigham Abbas Rizvi / Constantinos Kurt Wibmer / Poppy Mashilo / Mohammed Yousuf Ansari / Alison Burns / Shawn Barman / Fangzhu Zhao / Sohini Mukherjee / Jonathan L Torres / Souvick Chattopadhyay / Farha Mehdi / Jyoti Sutar / Deepak Kumar Rathore / Kamal Pargai / Janmejay Singh / Sudipta Sonar / Kamini Jakhar / Jyotsna Dandotiya / Sankar Bhattacharyya / Shailendra Mani / Sweety Samal / Savita Singh / Pallavi Kshetrapal / Ramachandran Thiruvengadam / Gaurav Batra / Guruprasad Medigeshi / Andrew B Ward / Shinjini Bhatnagar / Amit Awasthi / Devin Sok / Jayanta Bhattacharya /
PubMed AbstractAlthough 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 ...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.
External linksPLoS Pathog / PubMed:35482816 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.8 - 26.0 Å
Structure data

EMDB-26467: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up and 1 RDB down)
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-26470: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR26 (1 RBD up, 1 RBD down)
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-26472: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR26 (1 RBD up)
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-26473: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR26 (3 RBD down)
Method: EM (single particle) / Resolution: 26.0 Å

PDB-7z0x:
THSC20.HVTR26 Fab bound to SARS-CoV-2 Receptor Binding Domain
Method: X-RAY DIFFRACTION / Resolution: 1.8 Å

PDB-7z0y:
THSC20.HVTR04 Fab bound to SARS-CoV-2 Receptor Binding Domain
Method: X-RAY DIFFRACTION / Resolution: 2.95 Å

Chemicals

ChemComp-EPE:
4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / pH buffer*YM / HEPES

ChemComp-HOH:
WATER / Water

ChemComp-SO4:
SULFATE ION / Sulfate

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsANTIVIRAL PROTEIN / Neutralizing antibody / SARS-CoV-2 / Spike / RBD / IMMUNOLOGY / IMMUNE SYSTEM

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