Abstract
The porcine epidemic diarrhea virus (PEDV) is an Alphacoronavirus (α-CoV) that causes high mortality in infected piglets, resulting in serious economic losses in the farming industry. Hypericin is a dianthrone compound that has been shown as an antiviral activity on several viruses. Here, we first evaluated the antiviral effect of hypericin in PEDV and found the viral replication and egression were significantly reduced with hypericin post-treatment. As hypericin has been shown in SARS-CoV-2 that it is bound to viral 3CLpro, we thus established a molecular docking between hypericin and PEDV 3CLpro using different software and found hypericin bound to 3CLpro through two pockets. These binding pockets were further verified by another docking between hypericin and PEDV 3CLpro pocket mutants, and the fluorescence resonance energy transfer (FRET) assay confirmed that hypericin inhibits the PEDV 3CLpro activity. Moreover, the alignments of α-CoV 3CLpro sequences or crystal structure revealed that the pockets mediating hypericin and PEDV 3CLpro binding were highly conserved, especially in transmissible gastroenteritis virus (TGEV). We then validated the anti-TGEV effect of hypericin through viral replication and egression. Overall, our results push forward that hypericin was for the first time shown to have an inhibitory effect on PEDV and TGEV by targeting 3CLpro, and it deserves further attention as not only a pan-anti-α-CoV compound but potentially also as a compound of other coronaviral infections.
Highlights
We have shown that hypericin has an antiviral effect in infectious bronchitis virus (IBV) through apoptosis and reactive oxygen species (ROS) inhibition [23]
Another two groups utilized the molecular docking and dynamic stimulation that found hypericin precisely binds to SARS-CoV2 3C-like proteinase (3CLpro) catalytic site [8,9], indicating an antiviral effect of hypericin in SARS-CoV-2 infection
These results encouraged us to assess whether hypericin has a broad antiviral effect in different CoV sub-families; we explored the effect of hypericin on Porcine epidemic diarrhea virus (PEDV), an α-CoV
Summary
Coronaviruses (CoVs) are viruses that cause numerous pathologies in humans and other mammals, including respiratory, enteric, hepatic, and neurological diseases, with varying severities [1]. CoVs are divided into four genera, i.e., Alphacoronavirus (α-CoV), Betacoronavirus (β-CoV), Gammacoronavirus (γ-CoV), and Deltacoronavirus (δ-CoV). Porcine epidemic diarrhea virus (PEDV) is an α-CoV and the causative pathogen of porcine epidemic diarrhea (PED), which is mainly characterized by vomiting, watery diarrhea, severe dehydration, and weight loss [2]. PEDV infections have a substantially detrimental effect on the swine industry with high morbidity and mortality rates, especially in suckling piglets. In the past 10 years, new outbreaks of PED have swept through many countries in
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