In-Silico Molecular Docking, Validation, Drug-Likeness, and ADMET Studies of Antiandrogens to Use in the Fight against SARS-CoV-2

Document Type : Regular Article

Authors

1 1- Virology Unit, Immunovirology Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco. 2- Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik Hassan II University of Casablanca, Morocco.

2 1- Virology Unit, Immunovirology Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco. 2- Centre for Doctoral Studies in Health Sciences, Faculty of Medicine and Pharmacy, Casablanca, Morocco

3 1- Virology Unit, Immunovirology Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco 2- Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik Hassan II University of Casablanca, Morocco

4 1- National Center for Scientific and Technical Research (CNRST), Rabat 10102, Morocco 2- Department of Fundamental Sciences, School of Medicine, Mohammed VI University of Health Sciences, Casablanca, Morocco

5 1- Environmental Health Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco.

6 1- Immunology and Biodiversity Laboratory, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Morocco.

7 1- Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik Hassan II University of Casablanca, Morocco.

8 1- Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik Hassan II University of Casablanca, Morocco

9 1- Virology Unit, Immunovirology Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco.

10.22036/pcr.2022.324549.2016

Abstract

The SARS-CoV-2 is the novel coronavirus that causes the pandemic COVID-19, which has originated in Wuhan, China, in December 2019. Early studies have generally shown that human Angiotensin-Converting Enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are responsible for the viral entry of SARS-CoV-2 into target cells. TMPRSS2 as androgen-regulated is highly expressed in the prostate and other tissues including the lung. We investigated the interaction between the TMPRSS2 protein and selected antiandrogens, namely Bicalutamide, Enzalutamide, Apalutamide, Flutamide, Nilutamide, and Darolutamide using in-silico molecular docking. The results showed that Apalutamide (-8.8 Kcal/mol) and Bicalutamide (-8.6 Kcal/mol) had the highest docking score. The molecular docking process was validated by re-docking the peptide like-inhibitor-serine protease hepsin and superimposing them onto the reference complex. Last of all, the tested compounds have been evaluated for their pharmacokinetic and drug likeness properties and concluded that these compounds except Nilutamide (mutagenic) can be granted as potential inhibitors of SARS-CoV-2. This in-silico study result encourages its use as means for drug discovery of new COVID-19 treatment.

Graphical Abstract

In-Silico Molecular Docking, Validation, Drug-Likeness, and ADMET Studies of Antiandrogens to Use in the Fight against SARS-CoV-2

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History

  • Receive Date: 14 January 2022
  • Accept Date: 29 March 2022

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