Molecular docking and dynamics study to explore phytochemical ligand molecules against the main protease of SARS-CoV-2 from extensive phytochemical datasets

ABSTRACT

Background

The high transmission and pathogenicity of SARS-CoV-2 has led to a pandemic that has halted the world’s economy and health. The newly evolved strains and scarcity of vaccines has worsened the situation. The main protease (M^pro) of SARS-CoV-2 can act as a potential target due to its role in viral replication and conservation level.

Methods

In this study, we have enlisted more than 1100 phytochemicals from Asian plants based on deep literature mining. The compounds library was screened against the M^pro of SARS-CoV-2.

Results

The selected three ligands, Flemichin, Delta-Oleanolic acid, and Emodin 1-O-beta-D-glucoside had a binding energy of −8.9, −8.9, −8.7 KJ/mol respectively. The compounds bind to the active groove of the main protease at; Cys145, Glu166, His41, Met49, Pro168, Met165, Gln189. The multiple descriptors from the simulation study; root mean square deviation, root mean square fluctuation, radius of gyration, hydrogen bond, solvent accessible surface area confirms the stable nature of the protein-ligand complexes. Furthermore, post-md analysis confirms the rigidness in the docked poses over the simulation trajectories.

Conclusions

Our combinatorial drug design approaches may help researchers to identify suitable drug candidates against SARS-CoV-2.

KEYWORDS:

• SARS-CoV-2
• phytochemicals
• molecular docking
• admet
• molecular dynamics

Article highlights

1. The perceptible 1182 phytochemicals were retrieved from Asian plants after a rigorous literature review.

2. The molecular docking was performed against the M^pro to find a suitable drug candidate, where flemichin, delta-oleanolic acid, emodin 1-O-beta-D-glucoside had an energy of −8.9, −8.9, −8.7 KJ/mol, respectively.

3. With the help of ADMET filtering, the best three potential drug candidates were evaluated where no toxic and carcinogenic effects were found.

4. All the pharmacological prominences showed positive results, and no adverse effects were found.

5. The molecular dynamics simulation study helps to validate the docked interactions where stable conformations and rigid profiles of the docked complexes were observed.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.