Quest for Anti-SARS-CoV-2 antiviral therapeutics: in-silico and in-vitro analysis of edible mushroom- Cordyceps militaris

Background: The emergence and evolution of SARS-CoV-2 resulted a severe threat to public health globally. Due to the lack of an effective vaccine with durable immunity, the disease transited into the endemic phase, necessitating potent antiviral therapy including a scientific basis for current traditional herbal medicine. Objective: This study aimed to conduct a pharmacoinformatic analysis of selected chemical ingredients and in-vitro evaluation of Cordyceps militaris extract against SARS-CoV-2. Materials and methods: C. militaris, the widely used fungus in conventional herbal medicine, was subjected to computational investigation using molecular docking, molecular dynamic simulation and network pharmacology analysis followed by the in-vitro assay for evaluating its anti-SARS-CoV-2 potential. Results: The molecular docking analysis of C. militaris revealed the Cordycepin's highest affinity (−9.71 kcal/mol) than other molecules, i.e., Cicadapeptin-I, Cicadapeptin-II, Cordycerebroside-B, and N-Acetyl galactosamine to the receptor binding domain of the SARS-CoV-2 spike protein. C. militaris aqueous extract could reduce the SARS-CoV-2 viral copy numbers by 50.24% using crude extract at 100 μg/mL concentration. Conclusion: These findings suggest that C. militaris has promising anti-SARS-CoV-2 activity and may be explored as traditional medicine for managing the COVID-19 surge in the endemic phase.