Baicalin Inhibits Coxsackievirus B3 Replication by Reducing Cellular Lipid Synthesis

Abstract

Baicalin is a flavonoid extracted from Scutellariae Radix and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner in vitro at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation.

Characterization of the lipidomic profile of BmN cells in response to Bombyx mori cytoplasmic polyhedrosis virus infection

“…Glycerophospholipid metabolism is involved in the biosynthesis of PC and PE. An increasing number of studies have shown that disorders of glycerophospholipid metabolism in cells can lead to onset of diseases ( Bello-Perez et al, 2020 ; Wang et al, 2020 ). In this study, the metabolism of glycerophospholipids, especiallyPC(38:2) and PE(36:1) were found to be the most enriched pathway during BmCPV infection, indicating that glycerophospholipid metabolism may be crucial for the pathogenesis of BmCPV.…”

“…Zebrafish C-reactive protein-like protein inhibits spring viraemia of carp rhabdovirus replication by causing alterations of cholesterol ratios in the host cellular membranes ( Bello-Perez et al, 2020 ). Lipids have also been shown to play important roles in the replication of coxsackievirus B3 ( Wang et al, 2020 ). An increased level fatty acid biosynthesis coupled with accumulation of free fatty acids that are associated with virus replication has been observed in host cells following CSFV infection ( Ma et al, 2019 ).…”

Antiviral Properties of Baicalin: a Concise Review

“…The treatment of baicalin (1) reduced the level of FFA, CHO, Fasn acetyl-CoA carboxylase, and LC3-II (an autophagosome marker). Therefore, the result has concluded that the observed antiviral effect of baicalin on CVB3 might be mediated via suppressing lipid synthesis and inhibiting autophagosome generation (Wang et al 2020). The mechanisms implicated in the inhibitory effects of baicalin on viral pneumonia were also reported in the literature.…”

Research progress on antiviral constituents in traditional Chinese medicines and their mechanisms of action

“…Baicalin, baicalein, wogonin and wogonoside are the four major flavones in Huangqin and have various pharmacological functions, and have been widely investigated for their antiviral activities (Wang, Yang et al. 2020 ). Baicalein and baicalin down-regulated ZIKV replication 10 h after infection, and showed significant preventive effects in pre-treated cells.…”