A Novel Small Molecule Inhibits Hepatitis C Virus Propagation in Cell Culture

Oraby, Ahmed K.; Gardner, Cassandra L; Needle, Robert; Kofahi, Hassan M.; Everard, Kylie R; Taylor, Nathan; Rutihinda, Suzette G; Barry, Jacqueline P; Hirasawa, Kensuke; Georghiou, Paris E.; Russell, Rodney S.

doi:10.1128/spectrum.00439-21

Cited by 1 publication

(1 citation statement)

References 47 publications

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“…N-(4-hydroxyphenyl) retinamide (4-HPR) inhibits viral replication by inhibiting the transcription of the NS5 protein of DENV, but not through the PERK signal pathway [ 44 ]. A novel small-molecule compound (AO13) can inhibit replication of HCV, and might target the NS5B RNA polymerase [ 45 ]. Compound 147 can correct protein misfolding of ER, and the antiviral activity independent of ATF6 induction [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response

Wang

Yang

et al. 2023

Viruses

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Japanese encephalitis virus (JEV) infection causes host endoplasmic reticulum stress (ERS) reaction, and then induces cell apoptosis through the UPR pathway, invading the central nervous system and causing an inflammation storm. The endoplasmic reticulum stress inhibitor, 4-phenyl-butyric acid (4-PBA), has an inhibitory effect on the replication of flavivirus. Here, we studied the effect of 4-PBA on JEV infection both in vitro and vivo. The results showed that 4-PBA treatment could significantly decrease the titer of JEV, inhibit the expression of the JEV NS3 protein (in vitro, p < 0.01) and reduce the positive rate of the JEV E protein (in vivo, p < 0.001). Compared to the control group, 4-PBA treatment can restore the weight of JEV-infected mice, decrease the level of IL-1β in serum and alleviate the abnormalities in brain tissue structure. Endoplasmic reticulum stress test found that the expression level of GRP78 was much lower and activation levels of PERK and IRE1 pathways were reduced in the 4-PBA treatment group. Furthermore, 4-PBA inhibited the UPR pathway activated by NS3, NS4b and NS5 RdRp. The above results indicated that 4-PBA could block JEV replication and inhibit ER stress caused by JEV. Interestingly, 4-PBA could reduce the expression of NS5 by inhibiting transcription (p < 0.001), but had no effect on the expression of NS3 and NS4b. This result may indicate that 4-PBA has antiviral activity independent of the UPR pathway. In summary, the effect of 4-PBA on JEV infection is related to the inhibition of ER stress, and it may be a promising drug for the treatment of Japanese encephalitis.

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Section: Discussionmentioning

confidence: 99%