In-Silico Molecular Docking, Validation, Drug-Likeness, and ADMET Studies of Antiandrogens to Use in the Fight against SARS-CoV-2
A Saih, E Imane, H Baba, M Bouqdayr, H Ghazal, S Hamdi, S Moussamih, H Bennani, R Saile, A Kettani, L Wakrim
doi:10.22036/PCR.2022.324549.2016
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 -1 ) and bicalutamide (-8.6 Kcal mol -1 ) 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.
SUPPLEMENTARY MATERIALS Supplementary Table 1 : Molecular docking scores (in -Kcal mol -1 ) of TMPRSS2 protein with its selected inhibitors (ligands). Supplementary Table 2 : Identification of the active site of TMPRSS2 protein using the CASTp server Supplementary Table 3 : Drug likeness results of the six studied ligands. Supplementary Table 4 : pharmacokinetic parameters of the six tested compounds.
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