Title:Cordycepin as a Promising Inhibitor of SARS-CoV-2 RNA Dependent
RNA Polymerase (RdRp)
Volume: 29
Issue: 1
关键词:
虫草素，生物活性代谢物，药物再利用，SARS-CoV-2，COVID-19，分子动力学模拟。
摘要: 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).
