Computational screening of dual inhibitors from FDA approved antiviral drugs on SARS-CoV-2 spike protein and the main protease using molecular docking approach

Shanthi Sabarimurugan, Indu Purushothaman, Rajarajan Swaminathan, Arun Dharmarajan, Sudha Warrier, Sangeetha Kothandan

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Abstract

The deadly disease-causing novel coronavirus has recently swept across the world and endangered many human lives. Although, various research on therapeutic measures to solve this pandemic crisis has been published; no favourable results have been achieved. We propose the use of potential FDA-approved dual inhibitors which can inhibit two targets (either on entry-level or the main protease) for the effective treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We screened 12 FDA-approved antiviral inhibitors listed in Drug bank and analysed the ADMET properties of each drug of interest to study the bioavailability, safety and toxicity. Two potential targets, the spike protein and the main protease of SARS-CoV-2 obtained from PDB have been used for molecular docking. All the selected drugs were docked with both targets and demonstrated strong hydrogen bond (HB) interactions in multiple active sites. Amongst these, the range of binding energy was from 3-7 kcal/mol for spike protein and 2-8 kcal/mol for the main protease. Upon comparison of all the processed drugs ganciclovir and zanamivir displayed significant binding energy with HB interactions with both, spike (-9.2 and -9 kcal/mol respectively) and the main protease (-9 kcal/mol). Ribavirin and tenofovir showed significant binding energy above -8 kcal/mol with seven HB interactions with the main protease and also spike protein. The novel findings regarding the antiviral properties of these dual inhibitors using a computational approach will be a good starting point for the efficacy determination of these drugs for pre-clinical and clinical studies aimed at developing active antivirals to target SARS-CoV-2.

Original languageEnglish
Pages (from-to)160-172
Number of pages13
JournalActa Virologica: international journal
Volume65
Issue number2
DOIs
Publication statusPublished - 2021

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