Structure-based virtual screening, molecular dynamics and binding affinity calculations of some potential...

Area of Science:

• Computational chemistry and pharmacology
• Virology and infectious diseases
• Natural product drug discovery

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, has led to a global health crisis with significant mortality.
• Existing treatments for COVID-19 have shown severe toxicity and health hazards, necessitating the search for safer alternatives.
• There is an urgent need for novel, safe, and effective therapeutic compounds against SARS-CoV-2.

Purpose of the Study:

• To evaluate the potential of selected herbal compounds as inhibitors of SARS-CoV-2.
• To investigate the efficacy of glucoraphanin, vitexin, and niazinin against the virus's spike protein and main protease (3CLpro/Mpro) using in-silico methods.
• To assess the drug-likeness and safety profiles of these phytocompounds.

Main Methods:

• In-silico virtual studies including molecular docking, target analysis, toxicity prediction, and ADME prediction.
• Molecular-Dynamic (MD) simulation to support docking results and assess binding stability.
• Evaluation of phytocompounds against SARS-CoV-2 spike glycoprotein and 3CLpro (Mpro).

Main Results:

• Selective phytocompounds, including niazinin, vitexin, and glucoraphanin, successfully docked into the binding sites of SARS-CoV-2 spike glycoprotein and 3CLpro (Mpro).
• In-silico analyses predicted favorable solubility, pharmacodynamic properties, and target accuracy for these compounds.
• The identified hit molecules adhered to Lipinski's rule and demonstrated stable binding to viral target proteins.

Conclusions:

• The studied herbal compounds exhibit significant potential as safe and effective inhibitors of SARS-CoV-2.
• Niazinin, vitexin, and glucoraphanin are promising candidates for further investigation in biochemical and cell-based assays.
• These findings support the advancement of these phytocompounds towards clinical investigations for COVID-19 treatment.