Serine Protease Inhibitor AEBSF Reduces Dengue Virus Infection via Decreased Cholesterol Synthesis.

In this study, we set forth to investigate the anti-viral effect of five commercially available protease inhibitors on DENV infection since both viral and host proteases can contribute to effective viral replication. Previously, the serine protease inhibitor AEBSF [4-(2-aminoethyl) benzene sulfonyl fluoride] has been shown to inhibit DENV NS3 protease activity. The results of the present study revealed that DENV genome replication and protein synthesis were significantly inhibited by AEBSF in a dose-dependent manner. AEBSF inhibited the expression of genes such as 3-hydroxy 3-methyl-glutaryl-CoA synthase (HMGCS), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), and low-density lipoprotein receptor (LDLR). Moreover, AEBSF significantly inhibited HMGCR activity and intracellular cholesterol synthesis after DENV infection. The anti-DENV effect of AEBSF was confirmed in all four DENV serotypes and in three different cell lines. These results indicate that AEBSF reduces DENV infection via both viral and host protease activities.
PMID: 31386864 [PubMed - as supplied by publisher]

Source: Virus Research - August 2, 2019 Category: Virology Authors: Sreelatha L, Malakar S, Songprakhon P, Morchang A, Srisawat C, Noisakran S, Yenchitosomanus PT, Limjindaporn T Tags: Virus Res Source Type: research