Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells

Abstract

Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases. Currently, no specific drug is available for the treatment of DENV infection. Thus, the development of an anti-DENV drug is urgently required. Cordycepin (3′-deoxyadenosine), which is a major bioactive compound in Cordyceps (ascomycete) fungus that has been used for centuries in Chinese traditional medicine, was reported to exhibit antiviral activity. However, the anti-DENV activity of cordycepin is unknown. We hypothesized that cordycepin exerts anti-DENV activity and that, as an adenosine derivative, it inhibits DENV replication. To test this hypothesis, we investigated the anti-DENV activity of cordycepin in DENV-infected Vero cells. Cordycepin treatment significantly decreased DENV protein at a half-maximal effective concentration (EC50) of 26.94 μM. Moreover, DENV RNA was dramatically decreased in cordycepin-treated Vero cells, indicating its effectiveness in inhibiting viral RNA replication. Via in silico molecular docking, the binding of cordycepin to DENV non-structural protein 5 (NS5), which is an important enzyme for RNA synthesis, at both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, was predicted. The results of this study demonstrate that cordycepin is able to inhibit DENV replication, which portends its potential as an anti-dengue therapy.

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

“…, adenoviruses (AVs), dengue virus (DENV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), human immunodeficiency virus (HIV), human poliovirus (HPV), human rhinovirus (HRV), influenza viruses (IVs), Kyasanur Forest disease virus (KFDV), murine leukemia viruses (MLVs or MuLVs), murine sarcoma viruses (MSVs or MuSVs), Newcastle disease virus (NDV), Omsk hemorrhagic fever virus (OHFV), Powassan virus (POWV), rotaviruses (RV), vaccinia virus (VACV or VV), West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV). 33 , 34 , 39 − 43 These strong inhibitory activities extend to some plant viruses, such as cowpea chlorotic mottle virus (CCMV) and tobacco mosaic virus (TMV). 44 , 45 The strong antiviral actions of cordycepin are mediated through specific molecular mechanisms that mainly originate due to the extreme structural analogism with the nucleoside adenosine, as this analogism renders the human biological system unable to recognize this molecule, e.g.…”

Bioactive natural products in COVID-19 therapy

“…acute lung injury). Specifically, cordycepin is a promising therapeutic against several viruses in vitro, including dengue virus, (Panya et al, 2021) Epstein-Barr virus, (Choi et al, 2019) and hepatitis C virus. (Ueda et al, 2014).…”

Medicinal Fungi with Antiviral Effect

“…Panya et al, found that cordycepin can inhibit the replication of DENV and reduce the RNA level of the virus in Vero cells. Its antiviral effect is related to the replication of virus RNA in the later stage of virus infection [ 55 ]. In another study, five kinds of medicinal fungi Lignosus rhinocerotis , Pleurotus giganteus , Hericium erinaceus , Schizophyllum commune , and Ganoderma lucidium were extracted with hot aqueous and ethanol, and then extracted with n-hexane, ethyl acetate and water in turn.…”