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Discovery of Potent SARS-CoV-2 Inhibitors from Approved Antiviral Drugs via Docking and Virtual Screening

Author(s):

Samir Chtita *, Assia Belhassan, Adnane Aouidate, Salah Belaidi, Mohammed Bouachrine and Tahar Lakhlifi   Pages 1 - 14 ( 14 )

Abstract:


Background: Corona Virus Disease 2019 (COVID-19) pandemic threatens patients, societies and healthcare systems around the world. There is an emergent need to search for possible medications.

Objective: This article intends to use virtual screening and molecular docking methods to find potential inhibitors that can respond to COVID-19 from existing drugs.

Methods: To tack part in the current research investigation to define a potential target drug that may protect the world from emerged pandemic corona disease, we have carried out a virtual screening study by of 129 approved drugs that their metabolic characteristics, dosages used, potential efficacy and side effects are clear as they have been approved for treating existing infections. Especially 12 drugs against chronic hepatitis B virus, 37 against chronic hepatitis C virus, 37 against human immunodeficiency virus, 14 anti-herpesvirus, 11 anti- influenza, and 18 others drugs currently on the market were considered for this study. Then these drugs were evaluated using virtual screening and molecular docking studies in the active site of the (SARS-CoV-2) main protease (6lu7). Once the efficacy of the drug is determined, it can be approved for of their in vitro and in vivo activity against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that could be interesting for rapid clinical treatment of patients.

These drugs were ranked for potential effectiveness against SARS-CoV-2 and those with high molecular docking scores are proposed as novel candidates for repurposing. The N3 inhibitor co-crystallized with the protease (6lu7) and the anti-HIV protease inhibitor Lopinavir were used as standards for comparison.

Results: The results suggest the effectiveness of Beclabuvir, Nilotinib, Tirilazad, Trametinib and Glecaprevir as potent drugs against SARS-CoV-2 since they tightly bind to its main protease.

Conclusion: These promising drugs could inhibit the replication of the virus; hence, we suggest the repurposing of these compounds for thetreatment of COVID-19. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA. However, the assessment of these potential inhibitors as clinical drugs involves further in vivo tests for these drugs.

Keywords:

COVID-19, SARS-CoV-2, 6lu7, Antiviral, Docking, Virtual screening, Lopinavir.

Affiliation:

Laboratory of Physical Chemistry of Materials, Faculty of sciences Ben M’Sik, Hassan II University of Casablanca, B.P. 7955 Sidi Othmane, Casablanca, Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University, B.P. 11201 Zitoune, Meknes, Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University, B.P. 11201 Zitoune, Meknes, Laboratory of Molecular Chemistry and Environment, Group of Computational and pharmaceutical Chemistry, University of Biskra, BP145, 07000, Biskra, High School of Technology of Khenifra, Sultan Slimane University, B.P. 591, Khenifra, Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University, B.P. 11201 Zitoune, Meknes



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