Anti-COVID-19 terpenoid from marine sources: A docking, admet and molecular dynamics study

Nayim Sepay; Aishwarya Sekar; Umesh C Halder; Abdullah Alarifi; Mohd Afzal

doi:10.1016/j.molstruc.2020.129433

Anti-COVID-19 terpenoid from marine sources: A docking, admet and molecular dynamics study

J Mol Struct. 2021 Mar 15:1228:129433. doi: 10.1016/j.molstruc.2020.129433. Epub 2020 Oct 10.

Authors

Nayim Sepay¹, Aishwarya Sekar², Umesh C Halder¹, Abdullah Alarifi³, Mohd Afzal³

Affiliations

¹ Department of Chemistry, Jadavpur University, Kolkata-70032, India.
² Department of Bioinformatics, Stella Maris College (Autonomous), Chennai, Tamilnadu-600 086, India.
³ Catalytic Chemistry Research Chair, Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

Traditional medicines contain natural products (NPs) as main ingredient which always give new direction and paths to develop new advanced medicines. In the COVID-19 pandemic, NPs can be used or can help to find new compound against it. The SARS coronavirus-2 main protease (SARS CoV-2 M^pro) enzyme, arbitrate viral replication and transcription, is target here. The study show that, from the electronic features and binding affinity of all the NPs with the enzyme, the compounds with higher hydrophobicity and lower flexibility can be more favorable inhibitor. More than fifty NPs were screened for the target and one terpenoid (T3) from marine sponge Cacospongia mycofijiensis shows excellent SARS CoV-2 M^pro inhibitory activity in comparison with known peptide based inhibitors. The molecular dynamics simulation studies of the terpenoids with the protein indicates that the complex is stable and hydrogen bonds are involved during the complexation. Considering binding affinity, bioavailability, pharmacokinetics and toxicity of the compounds, it is proposed that the NP T3 can act as a potential drug candidate against COVID-19 virus.

Keywords: ADME; ATAD5, ATPase family AAA domain-containing protein 5; Ahr, aryl hydrocarbon receptor; Ar, androgen receptor; Ar-lbd, androgen receptor ligand binding domain; Cyto, cytotoxicity; Dili, hepatotoxicity carcino carcinogenicity; Docking; Er, estrogen receptor alpha; Er-lbd, estrogen receptor ligand binding domain; HSE, Heat shock factor response element; MMP, Mitochondrial Membrane Potential; Molecular dynamics; Mutagen, mutagenicity; Natural products; PPAR-Gamma, Peroxisome Proliferator Activated Receptor Gamma; Sars cov-2 mpro; Toxicity; nrf2/ARE, Nuclear factor (erythroid-derived 2)-like 2/antioxidant responsive element; sars, severe acute respiratory syndrome.