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. 2021 Sep 15:1240:130506.
doi: 10.1016/j.molstruc.2021.130506. Epub 2021 Apr 29.

Screening of cryptogamic secondary metabolites as putative inhibitors of SARS-CoV-2 main protease and ribosomal binding domain of spike glycoprotein by molecular docking and molecular dynamics approaches

G Prateeksha  1 , Tikam S Rana  2 , Ashish K Ashthana  2 , Saroj K Barik  1 , Brahma N Singh  1
Affiliations

Screening of cryptogamic secondary metabolites as putative inhibitors of SARS-CoV-2 main protease and ribosomal binding domain of spike glycoprotein by molecular docking and molecular dynamics approaches

G Prateeksha et al. J Mol Struct. .

Abstract

The unprecedented quick spreading of newly emerged SARS-CoV-2, the virus responsible for causing COVID-19 has put the whole world in vast crisis. Several prophylactic interventions are being performed to discover the effective anti-COVID-19 agent. Thus, the present study aims to identify the cryptogamic secondary metabolites (CSMs) as potent inhibitors of two major targets of SARS-Cov2, namely 3-chymotrypsin-like protease (3CLpro) and receptor-binding domain (RBD) of spike glycoprotein (SGP), by implementing a computational approach. Molecular docking was carried out on Autodock 4.2 software with the 3CLpro (PDB ID:6LU7) and RBD of SGP (PDB ID:6W41) of the virus. Lopinavir and Arbidol were taken as positive controls to compare the efficacy of randomly selected 53 CSMs. The drug-likeness and pharmacokinetics properties of all metabolites were accessed to discern the anti-COVID 19 activity acting well at the physiological conditions. The docking results predicted that Marchantin E and Zeorin would potentially block the catalytic site of 3CLpro with the interaction energy values of -8.42 kcal/mol and -9.04 kcal/mol, respectively. In addition, Usnic acid revealed its ability to combat the interaction of RBD of SGP to angiotensin-converting enzyme-2 in docking analysis. To certify the potent metabolites for both targets of SARS-CoV-2, MD analysis was performed for 100 ns. The results confirmed that Marchantin E could inhibit SARS-CoV-2 3CLpro and RBD of SGP as well as reveals excellent pharmacokinetic properties. The present study suggests that the identified CSMs could be quickly positioned for further experimental validation to propose promising inhibitors of SARS-CoV-2.

Keywords: Cryptogamic secondary metabolites; Main protease; Molecular docking; Molecular dynamics; Ribosomal binding domain; SARS-CoV-2.

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Conflict of interest statement

The authors declare that there are no conflicts of interest. Dr. Brahma Nand Singh reports financial support was provided by DBT and CSIR and DBT, India. Dr. B.N. Singh reports a relationship with CSIR-NBRI, Lucknow that includes: employment.

Figures

Image, graphical abstract
Graphical abstract
Fig. 1
Fig. 1
3D and 2D images of interaction pattern of 3CLpro-Marchantin E, 3CLpro-Zeorin and 3CLpro-Lopinavir.
Fig. 2
Fig. 2
3D and 2D images of interaction pattern of RBD-Marchantin E, RBD-Zeorin, RBD-Usnic acid and RBD-Arbidol.
Fig. 3
Fig. 3
RMSD graph of 3CLpro backbone (a) fixed with Marchantin E (blue line), Zeorin (green line) and Lopinavir (red line). RBD backbone of SGP (b) interacted with Marchantin E (blue line), Zeorin (green line), Usnic acid (purple line) and Arbidol (red line). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
Fig. 4
RMSF graph of main protease (a) complexed with marchantin E (blue line), Zeorin (green line) and Lopinavir (red line). RBD of SGP (b) bound with Marchantin E (blue line), Zeorin (green line), Usnic acid (purple line) and Arbidol (red line). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5
Fig. 5
Rg graphs of 3CLpro (a) complexed with Marchantin E (blue line), Zeorin (green line) and Lopinavir (red line). RBD of SGP (b) bound with Marchantin E (blue line), Zeorin (green line), Usnic acid (purple line) and Arbidol (red line). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 6
Fig. 6
Plots of intramolecular H_bond between (a) 3CLpro-Marchantin E (blue)/3CLpro-Zeorin (green)/ 3CLpro-Lopinavir (red) and (b) RBD-Marchantin E (blue)/ RBD-Zeorin (green)/ RBD-Usnic acid (purple) and RBD-Arbidol (red). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 7
Fig. 7
Per-residue energy decomposition analysis for 3CLpro (a) with Marchantin E (blue), Zeorin (green), and Lopinavir (red) and RBD (b) with Marchantin E (blue) Zeorin (green), RBD-Usnic acid, RBD-Arbidol. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
See this image and copyright information in PMC

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