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Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells.
Kumar, Vipul; Dhanjal, Jaspreet Kaur; Bhargava, Priyanshu; Kaul, Ashish; Wang, Jia; Zhang, Huayue; Kaul, Sunil C; Wadhwa, Renu; Sundar, Durai.
  • Kumar V; DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, New Delhi, India.
  • Dhanjal JK; AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
  • Bhargava P; AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
  • Kaul A; AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
  • Wang J; AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
  • Zhang H; AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
  • Kaul SC; AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
  • Wadhwa R; AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
  • Sundar D; DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, New Delhi, India.
J Biomol Struct Dyn ; 40(1): 1-13, 2022 01.
Article in English | MEDLINE | ID: covidwho-436584
Semantic information from SemMedBD (by NLM)
1. withaferin A INTERACTS_WITH TMPRSS2 protei
Subject
withaferin A
Predicate
INTERACTS_WITH
Object
TMPRSS2 protei
2. withanone INTERACTS_WITH TMPRSS2 protei
Subject
withanone
Predicate
INTERACTS_WITH
Object
TMPRSS2 protei
3. Decision PROCESS_OF World
Subject
Decision
Predicate
PROCESS_OF
Object
World
4. MCF-7 Cells LOCATION_OF TMPRSS2 gene|TMPRSS2
Subject
MCF-7 Cells
Predicate
LOCATION_OF
Object
TMPRSS2 gene|TMPRSS2
5. withanone INTERACTS_WITH TMPRSS2 gene|TMPRSS2
Subject
withanone
Predicate
INTERACTS_WITH
Object
TMPRSS2 gene|TMPRSS2
6. withaferin A INTERACTS_WITH TMPRSS2 protein, human|TMPRSS2
Subject
withaferin A
Predicate
INTERACTS_WITH
Object
TMPRSS2 protein, human|TMPRSS2
7. withanone INTERACTS_WITH TMPRSS2 protein, human|TMPRSS2
Subject
withanone
Predicate
INTERACTS_WITH
Object
TMPRSS2 protein, human|TMPRSS2
8. Decision PROCESS_OF World
Subject
Decision
Predicate
PROCESS_OF
Object
World
9. MCF-7 Cells LOCATION_OF TMPRSS2 gene|TMPRSS2
Subject
MCF-7 Cells
Predicate
LOCATION_OF
Object
TMPRSS2 gene|TMPRSS2
10. withanone INTERACTS_WITH TMPRSS2 gene|TMPRSS2
Subject
withanone
Predicate
INTERACTS_WITH
Object
TMPRSS2 gene|TMPRSS2
ABSTRACT
Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated world-wide, in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use.Communicated by Ramaswamy H. Sarma.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Proteinase Inhibitors / Virus Internalization / Withanolides / SARS-CoV-2 Type of study: Prognostic study / Risk factors Topics: Vaccines Limits: Humans Language: English Journal: J Biomol Struct Dyn Year: 2022 Document Type: Article Affiliation country: 07391102.2020.1775704

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Proteinase Inhibitors / Virus Internalization / Withanolides / SARS-CoV-2 Type of study: Prognostic study / Risk factors Topics: Vaccines Limits: Humans Language: English Journal: J Biomol Struct Dyn Year: 2022 Document Type: Article Affiliation country: 07391102.2020.1775704