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

Akalesh Kumar Verma, Akalesh Kumar Verma

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.

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

Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Docking structure and chemical interactions of cordycepin have been shown along with ligand atoms and interacting amino acids in the binding sites of the SARS-CoV-2 spike protein RBD.
Figure 2.
Figure 2.
Docking structure and chemical interactions of cordycepin have been shown along with ligand atoms and interacting amino acids in the binding sites of Mpro.
Figure 3.
Figure 3.
The interaction network of cordycepin was determined by STITCH algorithm, showing the involvement of cordycepin in multiple pathways. This is the confidence view; stronger associations are represented by thicker lines. Protein-protein interactions are shown in grey, chemical-protein interactions in green and interactions between chemicals in red.
Figure 4.
Figure 4.
Cordycepin mediated biological response for SARS-CoV-2 RNA degradation.

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