Screening of Natural Compounds as Inhibitor of Mpro SARS-CoV-2 Protein; A Molecular Dynamics Approach.

Background: New strains of SARS-CoV-2 are continually emerging worldwide. Recently, WHO warned of a severe new wave in Europe. Current vaccines cannot fully prevent reinfection in vaccinated individuals.

Aim: Given this issue, recent research focuses on new antiviral candidates with high efficacy and minimal side effects.

Objectives: Screen natural compounds as inhibitors of Mpro SARS-CoV-2 protein using molecular dynamics.

Methods: In this study, we have screened the potential of plant-based natural anti-viral compounds. A library of the 579 compounds was generated using currently available literature and online databases. All these compounds were screened based on their binding affinities as predicted by molecular docking analysis and compounds having binding affinity values ≤ -10 Kcal/mol were considered for analysis. Furthermore, from physicochemical assessment, drug-likeness initially nine compounds were identified as the antiviral targets for the selected viral proteins. After ADMET analysis and simulations, the compound 9064 with the lowest RMSD, Coul-SR interaction energy (-71.53 kJ/mol), and LJ-SR energy (-95.32 kJ/mol) was selected as the most stable drug candidate against COVID-19 main protease Mpro.

Results: The ΔG value, calculated using MMGBSA also revealed strong binding of the compound with Mpro. The selected antiviral compound 9064 is an antioxidant flavonoid (Catechin or Cianidanol), which was previously known to have significant immunomodulatory, anti-inflammatory, and antioxidant properties.

Conclusion: Considering the limitations of currently available vaccines, our study may provide new insight into potential drugs that may prevent SARS-CoV-2 infection in humans.