Viruses, Vol. 13, Pages 1825: Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease

Viruses, Vol. 13, Pages 1825: Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease Viruses doi: 10.3390/v13091825 Authors: Yue Zhang Huijie Chen Mengmeng Zou Rick Oerlemans Changhao Shao Yudong Ren Ruili Zhang Xiaodan Huang Guangxing Li Yingying Cong 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 throu...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research