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Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex
Ravikanth Vishnubhotla; Naveen Vankadari; Vijayasarathy Ketavarapu; Ramars Amanchy; Steffie Avanthi; Govardhan Bale; Duvvur Nageshwar Reddy; Mitnala Sasikala.
Afiliação
  • Ravikanth Vishnubhotla; Institute of Translational Research, Department of Genomics and Molecular Biology, Asian Institute of Gastroenterology and AIG Hospitals, Gachibowli, Hyderabad
  • Naveen Vankadari; Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
  • Vijayasarathy Ketavarapu; Institute of Translational Research, Department of Genomics and Molecular Biology, Asian Institute of Gastroenterology and AIG Hospitals, Gachibowli, Hyderabad
  • Ramars Amanchy; Division of Applied Biology, CSIR-IICT (Indian Institute of Chemical Technology), Ministry of Science and Technology (GOI), Hyderabad 500007, Telangana, India
  • Steffie Avanthi; Institute of Translational Research, Department of Genomics and Molecular Biology, Asian Institute of Gastroenterology and AIG Hospitals, Gachibowli, Hyderabad
  • Govardhan Bale; Institute of Translational Research, Department of Genomics and Molecular Biology, Asian Institute of Gastroenterology and AIG Hospitals, Gachibowli, Hyderabad
  • Duvvur Nageshwar Reddy; Institute of Translational Research, Department of Genomics and Molecular Biology, Asian Institute of Gastroenterology and AIG Hospitals, Gachibowli, Hyderabad
  • Mitnala Sasikala; AIG Hospitals
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-179663
ABSTRACT
SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 for activation and entry. With the aid of whole-exome sequencing, we report a variant rs12329760 in TMPRSS2 gene and its mutant V160M, which might impede viral entry. Furthermore, we identified TMPRSS2 cleavage sites in S2 domain of spike glycoprotein and report the structure of TMPRSS2 in complex with spike glycoprotein. We also report the structures of protease inhibitors in complex with TMPRSS2, which could hamper the interaction with spike protein. These findings advance our understanding on the role of TMPRSS2 and in the development of potential therapeutics.Competing Interest StatementThe authors have declared no competing interest.View Full Text
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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
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