Cordycepin as a Promising Inhibitor of SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp).

BACKGROUND: SARS-CoV-2, which emerged in Wuhan, China, is a new global threat that has killed millions of people and continues to do so. This pandemic has not only threatened human life but has also triggered economic downturns across the world. Researchers have made significant strides in discovering molecular insights into SARSCoV- 2 pathogenesis and developing vaccines, but there is still no successful cure for SARS-CoV-2 infected patients. OBJECTIVE: The present study has proposed a drug-repositioning pipeline for the design and discovery of an effective fungal-derived bioactive metabolite as a drug candidate against SARS-CoV-2. METHODS: Fungal derivative "Cordycepin" was selected for this study to investigate the inhibitory properties against RNA-dependent RNA polymerase (RdRp) (PDB ID: 6M71) of SARS-CoV-2. The pharmacological profile, intermolecular interactions, binding energy, and stability of the compound were determined utilizing cheminformatic approaches. Subsequently, molecular dynamic simulation was performed to better understand the binding mechanism of cordycepin to RdRp. RESULTS: The pharmacological data and retrieved molecular dynamics simulations trajectories suggest excellent drug-likeliness and greater structural stability of cordycepin, while the catalytic residues (Asp760, Asp761), as well as other active site residues (Trp617, Asp618, Tyr619, Trp800, Glu811) of RdRp, showed better stability during the overall simulation span. CONCLUSION: Promising results of pharmacological investigation along with molecular simulations revealed that cordycepin exhibited strong inhibitory potential against SARSCoV- 2 polymerase enzyme (RdRp). Hence, cordycepin should be highly recommended to test in a laboratory to confirm its inhibitory potential against the SARS-CoV-2 polymerase enzyme (RdRp).

Impact of Traditional Plants and their Secondary Metabolites in the Discovery of COVID-19 Treatment.

BACKGROUND: Coronavirus Disease-2019 belongs to the family of viruses which cause serious pneumonia along with fever, breathing issues and infection of lungs, and was first reported in China and later spread worldwide. OBJECTIVE: Several studies and clinical trials have been conducted to identify potential drugs and vaccines for Coronavirus Disease-2019. The present study listed natural secondary metabolites identified from plant sources with antiviral properties and could be a safer and tolerable treatment for Coronavirus Disease-2019. METHODS: A comprehensive search on the reported studies was conducted using different search engines such as Google Scholar, SciFinder, Sciencedirect, Medline PubMed, and Scopus for the collection of research articles based on plant-derived secondary metabolites, herbal extracts, and traditional medicine for coronavirus infections. RESULTS: Status of COVID-19 worldwide and information of important molecular targets involved in COVID- 19 are described, and through literature search, it is highlighted that numerous plant species and their extracts possess antiviral properties and are studied with respect to coronavirus treatments. Chemical information, plant source, test system type with a mechanism of action for each secondary metabolite are also mentioned in this review paper. CONCLUSION: The present review has listed plants that have presented antiviral potential in the previous coronavirus pandemics and their secondary metabolites, which could be significant for the development of novel and a safer drug which could prevent and cure coronavirus infection worldwide.