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).