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. 2021 Jul;39(10):3627-3637.
doi: 10.1080/07391102.2020.1769733. Epub 2020 Jun 1.

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

Muhammad Tahir Khan  1 , Arif Ali  2 , Qiankun Wang  2 , Muhammad Irfan  3 , Abbas Khan  2 , Muhammad Tariq Zeb  4 , Yu-Juan Zhang  5 , Sathishkumar Chinnasamy  2 , Dong-Qing Wei  2   6
Affiliations

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

Muhammad Tahir Khan et al. J Biomol Struct Dyn. 2021 Jul.

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 (Mpro) (PDB ID 6MO3). The crystallographic structure of Mpro 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.

Keywords: COVID-19; Marine drugs; dock; interactions; molecular dynamics.

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Figures

Figure 1.
Figure 1.
Structure of marine compounds. C-1 CID 11170714 containing halogen group (Br). These marine drugs have been identified in the previous study (Felix et al., 2017), active against latent Mycobacterium tuberculosis isolates. The drug has been observed as potent against Mpro, forming many hydrogen and hydrophobic interactions.
Figure 2.
Figure 2.
Interaction between C-1 CID 11170714 and Mpro apo. Drug has been shown, enclosed in black color blanket, signifying the binding pocket (Vilar et al., 2008).
Figure 3.
Figure 3.
COVID-19 Mpro residues forming hydrogen and hydrophobic interactions with five marine compounds. Compound C1 CID 11170714 exhibited more hydrogen and hydrophobic interactions. C2 interaction with Cys145, the active site of SARS-CoV 3CLpro creating a catalytic dyad (Cys145 and His41).
Figure 4.
Figure 4.
Interaction of C1 after MD simulation. Residues, Ser46, Met49, Asp187, Gln192, Ala194, Thr169, and Gln189, are involved in hydrogen bonding.
Figure 5.
Figure 5.
RSMD and RMSF of Mpro in complex with C1 compound. The complex exhibited a stable RMSD and RMSF during a 100 ns MD simulation period.
Figure 6.
Figure 6.
RMSD and RMSF of compound C1.
Figure 7.
Figure 7.
Distance matrix between C1 and Mpro during 100 ns (100,000 ps).
Figure 8.
Figure 8.
Radius of gyration. The degree of folding is constant during the whole simulation period.
None
See this image and copyright information in PMC

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