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Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (Mpro) of SARS-CoV-2 and inhibit its activity.
Kumar, Vipul; Dhanjal, Jaspreet Kaur; Kaul, Sunil C; Wadhwa, Renu; Sundar, Durai.
  • Kumar V; DAILAB, Department of Biochemical Engineering & 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.
  • 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 & Biotechnology, Indian Institute of Technology (IIT) Delhi, New Delhi, India.
J Biomol Struct Dyn ; 39(11): 3842-3854, 2021 07.
Article in English | MEDLINE | ID: covidwho-324383
Semantic information from SemMedBD (by NLM)
1. Caffeic Acid Phenethyl Ester INTERACTS_WITH Peptide Hydrolases
Subject
Caffeic Acid Phenethyl Ester
Predicate
INTERACTS_WITH
Object
Peptide Hydrolases
2. withanone INTERACTS_WITH Peptide Hydrolases
Subject
withanone
Predicate
INTERACTS_WITH
Object
Peptide Hydrolases
3. Peptide Hydrolases PART_OF 2019 novel coronavirus
Subject
Peptide Hydrolases
Predicate
PART_OF
Object
2019 novel coronavirus
4. Withania somnifera (plant) LOCATION_OF Withanolides
Subject
Withania somnifera (plant)
Predicate
LOCATION_OF
Object
Withanolides
5. withaferin A NEG_INTERACTS_WITH Protease Inhibitors
Subject
withaferin A
Predicate
NEG_INTERACTS_WITH
Object
Protease Inhibitors
6. Peptide Hydrolases PART_OF Genus: Coronavirus
Subject
Peptide Hydrolases
Predicate
PART_OF
Object
Genus: Coronavirus
7. Laboratory LOCATION_OF Validation
Subject
Laboratory
Predicate
LOCATION_OF
Object
Validation
8. Pharmaceutical Preparations TREATS Disease
Subject
Pharmaceutical Preparations
Predicate
TREATS
Object
Disease
9. Caffeic Acid Phenethyl Ester INTERACTS_WITH Peptide Hydrolases
Subject
Caffeic Acid Phenethyl Ester
Predicate
INTERACTS_WITH
Object
Peptide Hydrolases
10. withanone INTERACTS_WITH Peptide Hydrolases
Subject
withanone
Predicate
INTERACTS_WITH
Object
Peptide Hydrolases
11. Peptide Hydrolases PART_OF 2019 novel coronavirus
Subject
Peptide Hydrolases
Predicate
PART_OF
Object
2019 novel coronavirus
12. Withania somnifera (plant) LOCATION_OF Withanolides
Subject
Withania somnifera (plant)
Predicate
LOCATION_OF
Object
Withanolides
13. withaferin A NEG_INTERACTS_WITH Protease Inhibitors
Subject
withaferin A
Predicate
NEG_INTERACTS_WITH
Object
Protease Inhibitors
14. Peptide Hydrolases PART_OF Genus: Coronavirus
Subject
Peptide Hydrolases
Predicate
PART_OF
Object
Genus: Coronavirus
15. Laboratory LOCATION_OF Validation
Subject
Laboratory
Predicate
LOCATION_OF
Object
Validation
16. Pharmaceutical Preparations TREATS Disease
Subject
Pharmaceutical Preparations
Predicate
TREATS
Object
Disease
ABSTRACT
The recent novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV) has caused a large number of deaths around the globe. There is an urgent need to understand this new virus and develop prophylactic and therapeutic drugs. Since drug development is an expensive, intense and time-consuming path, timely repurposing of the existing drugs is often explored wherein the research avenues including genomics, bioinformatics, molecular modeling approaches offer valuable strengths. Here, we have examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) (active withanolides of Ashwagandha) and Caffeic Acid Phenethyl Ester (CAPE, bioactive ingredient of propolis) to a highly conserved protein, Mpro of SARS-CoV-2. We found that Wi-N and CAPE, but not Wi-A, bind to the substrate-binding pocket of SARS-CoV-2 Mpro with efficacy and binding energies equivalent to an already claimed N3 protease inhibitor. Similar to N3 inhibitor, Wi-N and CAPE were interacting with the highly conserved residues of the proteases of coronaviruses. The binding stability of these molecules was further analyzed using molecular dynamics simulations. The binding free energies calculated using MM/GBSA for N3 inhibitor, CAPE and Wi-N were also comparable. Data presented here predicted that these natural compounds may possess the potential to inhibit the functional activity of SARS-CoV-2 protease (an essential protein for virus survival), and hence (i) may connect to save time and cost required for designing/development, and initial screening for anti-COVID drugs, (ii) may offer some therapeutic value for the management of novel fatal coronavirus disease, (iii) warrants prioritized further validation in the laboratory and clinical tests.Communicated by Ramaswamy H. Sarma.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Risk factors Limits: Humans Language: English Journal: J Biomol Struct Dyn Year: 2021 Document Type: Article Affiliation country: 07391102.2020.1772108

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Risk factors Limits: Humans Language: English Journal: J Biomol Struct Dyn Year: 2021 Document Type: Article Affiliation country: 07391102.2020.1772108