Cordycepin: a bioactive metabolite of C ordyceps militaris and polyadenylation inhibitor with therapeutic potential against COVID-19

J Biomol Struct Dyn. 2022 May;40(8):3745-3752. doi: 10.1080/07391102.2020.1850352. Epub 2020 Nov 23.


Spike protein and main proteases of SARS-CoV-2 have been identified as potential therapeutic targets and their inhibition may lead to the reticence of viral entry and replication in the host body. Despite several efforts; till now no specific drugs are available to treat SARS-CoV-2. Considering all these challenges, the main objective of the present study was to establish therapeutic potential of cordycepin against COVID-19 as a conventional therapeutic strategy. In the present study; molecular interaction study was performed to assess potential binding affinity of cordycepin with SARS-CoV-2 target proteins using computational approach. Additionally, network pharmacology was used to understand cordycepin-protein interactions and their associated pathways in human body. Cordycepin is under clinical trial (NCT00709215) and possesses structural similarity with adenosine except that, it lacks a 3' hydroxyl group in its ribose moiety and hence it served as a poly(A) polymerase inhibitor and terminate premature protein synthesis. Additionally, it is known that functional RNAs of SARS-CoV-2 genome are highly 3'-plyadenylated and leading to synthesis of all viral proteins and if cordycepin can destabilize SARS-CoV-2 RNAs by inhibiting polyadenylation process then it may step forward in terms of inhibition of viral replication and multiplication in the host. Moreover, cordycepin showed strong binding affinity with SARS-CoV-2 spike protein (-145.3) and main proteases (-180.5) that further corroborate therapeutic potential against COVID-19. Since cordycepin has both pre-clinical and clinical information about antiviral activities, therefore; it is suggested to the world community to undertake repurposing cordycepin to test efficacy and safety for the treatment of COVID-19.

Keywords: SARS-CoV-2; 2019nCov; Coronavirus; main proteases; spike protein.

MeSH terms

  • Antiviral Agents / chemistry
  • COVID-19* / drug therapy
  • Clinical Trials as Topic
  • Cordyceps* / metabolism
  • Deoxyadenosines
  • Humans
  • Peptide Hydrolases / metabolism
  • Polyadenylation
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus


  • Antiviral Agents
  • Deoxyadenosines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptide Hydrolases
  • cordycepin

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