Title:Current Insights and Molecular Docking Studies of the Drugs under Clinical Trial
as RdRp Inhibitors in COVID-19 Treatment
Volume: 28
Issue: 46
Author(s): Irine Pauly, Ankit Kumar Singh, Adarsh Kumar, Yogesh Singh, Suresh Thareja, Mohammad A. Kamal, Amita Verma*Pradeep Kumar*
Affiliation:
- Bioorganic and Medicinal Chemistry Research Laboratory, Department of
Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, 211007, India
- Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, 151401, India
Keywords:
SARS-CoV-2, COVID-19, RdRp, remdesivir, life cycle, docking and simulation.
Abstract:
Study Background & Objective: After the influenza pandemic (1918), COVID-19 was declared a Vth
pandemic by the WHO in 2020. SARS-CoV-2 is an RNA-enveloped single-stranded virus. Based on the structure
and life cycle, Protease (3CLpro), RdRp, ACE2, IL-6, and TMPRSS2 are the major targets for drug development
against COVID-19. Pre-existing several drugs (FDA-approved) are used to inhibit the above targets in
different diseases. In coronavirus treatment, these drugs are also in different clinical trial stages. Remdesivir
(RdRp inhibitor) is the only FDA-approved medicine for coronavirus treatment. In the present study, by using
the drug repurposing strategy, 70 preexisting clinical or under clinical trial molecules were used in scrutiny for
RdRp inhibitor potent molecules in coronavirus treatment being surveyed via docking studies. Molecular simulation
studies further confirmed the binding mechanism and stability of the most potent compounds.
Material and Methods: Docking studies were performed using the Maestro 12.9 module of Schrodinger software
over 70 molecules with RdRp as the target and remdesivir as the standard drug and further confirmed by
simulation studies.
Results: The docking studies showed that many HIV protease inhibitors demonstrated remarkable binding interactions
with the target RdRp. Protease inhibitors such as lopinavir and ritonavir are effective. Along with
these, AT-527, ledipasvir, bicalutamide, and cobicistat showed improved docking scores. RMSD and RMSF
were further analyzed for potent ledipasvir and ritonavir by simulation studies and were identified as potential
candidates for corona disease.
Conclusion: The drug repurposing approach provides a new avenue in COVID-19 treatment.
