tetano
Editor, Senior Moderator
J Mol Struct
. 2020 Oct 10;129433.
doi: 10.1016/j.molstruc.2020.129433. Online ahead of print.
Anti-COVID-19 terpenoid from marine sources: a docking, ADMET and molecular dynamics study
Nayim Sepay[SUP] 1 [/SUP], Aishwarya Sekar[SUP] 2 [/SUP], Umesh C Halder[SUP] 1 [/SUP], Abdullah Alarifi[SUP] 3 [/SUP], Mohd Afzal[SUP] 3 [/SUP]
Affiliations
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[SUP]pro[/SUP]) 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[SUP]pro[/SUP] 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; AR, Androgen Receptor; AR-LBD, Androgen Receptor Ligand Binding Domain; ATAD5, ATPase family AAA domain-containing protein 5; AhR, Aryl hydrocarbon Receptor; Docking; ER, Estrogen Receptor Alpha; ER-LBD, Estrogen Receptor Ligand Binding Domain; HSE, Heat shock factor response element; MMP, Mitochondrial Membrane Potential; Molecular Dynamics; Natural Products; PPAR-Gamma, Peroxisome Proliferator Activated Receptor Gamma; SARS CoV-2 Mpro; SARS, Severe acute respiratory syndrome; Toxicity; cyto, Cytotoxicity; dili, Hepatotoxicity carcino Carcinogenicity; mutagen, Mutagenicity; nrf2/ARE, Nuclear factor (erythroid-derived 2)-like 2/antioxidant responsive element.
. 2020 Oct 10;129433.
doi: 10.1016/j.molstruc.2020.129433. Online ahead of print.
Anti-COVID-19 terpenoid from marine sources: a docking, ADMET and molecular dynamics study
Nayim Sepay[SUP] 1 [/SUP], Aishwarya Sekar[SUP] 2 [/SUP], Umesh C Halder[SUP] 1 [/SUP], Abdullah Alarifi[SUP] 3 [/SUP], Mohd Afzal[SUP] 3 [/SUP]
Affiliations
- PMID: 33071352
- PMCID: PMC7547581
- DOI: 10.1016/j.molstruc.2020.129433
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[SUP]pro[/SUP]) 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[SUP]pro[/SUP] 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; AR, Androgen Receptor; AR-LBD, Androgen Receptor Ligand Binding Domain; ATAD5, ATPase family AAA domain-containing protein 5; AhR, Aryl hydrocarbon Receptor; Docking; ER, Estrogen Receptor Alpha; ER-LBD, Estrogen Receptor Ligand Binding Domain; HSE, Heat shock factor response element; MMP, Mitochondrial Membrane Potential; Molecular Dynamics; Natural Products; PPAR-Gamma, Peroxisome Proliferator Activated Receptor Gamma; SARS CoV-2 Mpro; SARS, Severe acute respiratory syndrome; Toxicity; cyto, Cytotoxicity; dili, Hepatotoxicity carcino Carcinogenicity; mutagen, Mutagenicity; nrf2/ARE, Nuclear factor (erythroid-derived 2)-like 2/antioxidant responsive element.