Marine natural compounds as potents inhibitors against the main protease of SARS-CoV-2—a molecular dynamic study

Abstract

Sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA (ssRNA) virus, responsible for severe acute respiratory disease (COVID-19). A large number of natural compounds are under trial for screening compounds, possessing potential inhibitory effect against the viral infection. Keeping in view the importance of marine compounds in antiviral activity, we investigated the potency of some marine natural products to target SARS-CoV-2 main protease (M^pro) (PDB ID 6MO3). The crystallographic structure of M^pro in an apo form was retrieved from Protein Data Bank and marine compounds from PubChem. These structures were prepared for docking and the complex with good docking score was subjected to molecular dynamic (MD) simulations for a period of 100 ns. To measure the stability, flexibility, and average distance between the target and compounds, root mean square deviations (RMSD), root mean square fluctuation (RMSF), and the distance matrix were calculated. Among five marine compounds, C-1 (PubChem CID 11170714) exhibited good activity, interacting with the active site and surrounding residues, forming many hydrogen and hydrophobic interactions. The C-1 also attained a stable dynamic behavior, and the average distance between compound and target remains constant. In conclusion, marine natural compounds may be used as a potential inhibitor against SARS-CoV-2 for better management of COVID-19.

Graphical Abstract

Keywords:

• Marine drugs
• COVID-19
• dock
• interactions
• molecular dynamics

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgements

The current study as technically supported by Director PTRL KP, Peshawar, Dr. Sajid Ali, Molecular biologist, and Anwar Sheed Khan, microbiologist. Conceptualization was carried out by DQW, GS, and MTK; data curation by MTK, AA, QW, and SC; experimental work by MTK, QW, AA, and AK; formal analysis by AA, SC, and MTK; funding acquisition by DQW and approval by DQW and GS.

Additional information

Funding

Dong-Qing Wei is supported by the grants from the Key Research Area Grant 2016YFA0501703 of the Ministry of Science and Technology of China, the National Natural Science Foundation of China (Contract no. 61832019, 61503244), the Science and Technology Commission of Shanghai Municipality (Grant: 19430750600), the Natural Science Foundation of Henan Province (162300410060), and Joint Research Funds for Medical and Engineering and Scientific Research at Shanghai Jiao Tong University (YG2017ZD14). The computations were partially performed at the Peng Cheng Lab and the Center for High-Performance Computing, Shanghai Jiao Tong University.