Cordycepin: a bioactive metabolite of C ordyceps 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 0 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.

Potent Inhibitory Activities of the Adenosine Analogue Cordycepin on SARS-CoV-2 Replication

“…Cordycepin is a promising potential comprehensive anti-COVID-19 agent that should be put under the microscope in the coming days. Some new studies reported the in silico inhibitory activities of cordycepin on SARS-CoV-2 spike (S) protein and main protease (M pro ) enzyme, 46 , 56 , 57 and, recently, another computational study showed the in silico inhibitory activities of cordycepin on the SARS-CoV-2 RdRp enzyme. 47 In light of the findings of the previous in silico studies and the current in vitro study, it is proven that the cordycepin molecule has interesting superiority and advantage over most of the other investigational anti-SARS-CoV-2 molecules, especially those acting only on the S protein and/or M pro enzyme, as, first, it acts via the expected synergistic triple anti-SARS-CoV-2 mode of action ( i.e.…”

“…, acts as a polyadenylation inhibitor), severe shortening of poly(A) tails, continuous destabilization of mRNAs, strong purine biosynthesis inhibition, and also premature termination of protein synthesis. 33 , 36 , 46 …”

Antioxidant Activity of Mushroom Extracts/Polysaccharides—Their Antiviral Properties and Plausible AntiCOVID-19 Properties

“…This mushroom inhibited viral-induced membrane fusion, and could act against the early stages of HSV viral infection. The aqueous extracts of I. obliquus could prevent HSV-1 entry by directly acting on viral glycoproteins, which in turn prevent membrane fusion [ 321 ]. With a host of accomplishments against various reputed viruses, IO does stand a chance against COVID, yet has a long way to go.…”

Medicinal Fungi with Antiviral Effect

“…Verma et al, studied the molecular interaction between cordycepin, a key component of Cordyceps sinensis , and novel coronavirus-related target protein by molecular dynamics simulation, and found that cordycepin had strong binding force with RBD domain of novel coronavirus spike protein. This suggests that cordycepin may be used as a pan coronavirus fusion inhibitor targeting spike proteins to limit the entry of the virus into the body [ 17 ].…”