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

ABSTRACT

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.