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.
Highlights
Dengue virus (DENV) infection is one of the most rapidly spreading arboviral diseases of humans in the world [1]
To test the hypothesis that cordycepin is able to inhibit DENV infection, Vero cells were infected with DENV2 and a time-of-addition assay was performed
The Vero cells were treated with cordycepin (Figure 1a) at different times, including before, during, and after infection with DENV2, which were referred to as preinfection, coinfection, and postinfection, respectively
Summary
Dengue virus (DENV) infection is one of the most rapidly spreading arboviral diseases of humans in the world [1]. Natural compounds from herbs and medicinal plants are recognized for their safety and effectiveness, and many of them have been used as traditional medicines by people from many countries around the world Since these natural compounds often contain a broad spectrum of biological activities, they have the potential to be further purified and developed into drugs for the treatment of many human disease conditions. Cordycepin (30 -deoxyadenosine) is an adenosine derivative, and a major bioactive compound in Cordyceps sinensis and Cordyceps militaris This compound was previously reported to have antiviral activity [13,14,15,16,17]. This inhibitory effect was observed when a C. militaris extract was tested
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