Title:Discovery of Potent SARS-CoV-2 Inhibitors from Approved Antiviral Drugs via Docking and Virtual Screening
Volume: 24
Issue: 3
Author(s): Samir Chtita *, Assia Belhassan, Adnane Aouidate, Salah Belaidi, Mohammed Bouachrine and Tahar Lakhlifi
Affiliation:
- Laboratory of Physical Chemistry of Materials, Faculty of sciences Ben M’Sik, Hassan II University of Casablanca, B.P. 7955 Sidi Othmane, Casablanca,Morocco
Keywords:
COVID-19, SARS-CoV-2, 6lu7, antiviral, docking, virtual screening, lopinavir.
Abstract:
Background: Coronavirus Disease 2019 (COVID-19) pandemic continues to threaten
patients, societies and healthcare systems around the world. There is an urgent need to search for
possible medications.
Objective: This article intends to use virtual screening and molecular docking methods to find
potential inhibitors from existing drugs that can respond to COVID-19.
Methods: To take part in the current research investigation and to define a potential target
drug that may protect the world from the pandemic of corona disease, a virtual screening
study of 129 approved drugs was carried out which showed 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 other drugs currently on the market were
considered for this study. These drugs were then evaluated using virtual screening and
molecular docking studies on the active site of the (SARS-CoV-2) main protease (6lu7). Once
the efficacy of the drug is determined, it can be approved for its in vitro and in vivo
activity against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which
can be beneficial for the rapid clinical treatment of patients.
These drugs were considered potentially effective against SARS-CoV-2 and those with high
molecular docking scores were proposed as novel candidates for repurposing. The N3 inhibitor cocrystallized
with 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 can inhibit the replication of the virus; hence, the repurposing
of these compounds is suggested for the treatment 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 requires further in vivo tests
of these drugs.
