PS1097

PS1097 is a broad-spectrum antiviral inhibitor with an IC50 of 0.64 μM for BVDV RdRp. It selectively reduces RTN3 protein levels, partially decreases RTN3 mRNA, and does not affect other endoplasmic reticulum-resident proteins. PS1097 inhibits the replication of pestiviruses and various viruses that use the endoplasmic reticulum as a replication hub. It inhibits the enzymatic activity of BVDV RdRp and is active against bovine viral diarrhea virus. PS1097 is applicable in research related to infections by Zika virus, Usutu virus, West Nile virus, COVID-19, coxsackievirus B5, chikungunya virus, and vaccinia virus.

PS1097 exhibits strong antiviral effects against various viruses. It effectively inhibits the replication of the ZIKV Brazil/2016/INMI1 strain in Huh-7 cells with an EC₅₀ of 0.69 μM and a high selectivity index (SI) of 331.7. With starting serial dilutions of 100 μM for 48 hours, PS1097 demonstrates a broad-spectrum antiviral activity against various RNA and DNA viruses that rely on endoplasmic reticulum remodeling, showing EC₅₀ values ranging from 0.1 to 5.51 μM across susceptible virus-cell line combinations, maintaining high selectivity indices in most systems. Additionally, PS1097 (0.6-6 μM; 48 h) dose-dependently inhibits the synthesis of the ZIKV NS5 protein in Huh-7 and Vero E6 cells, with maximum inhibition at 6 μM. It also selectively downregulates reticulon 3 protein levels in Huh-7 cells at 6 μM over 48 hours, while only partially reducing reticulon 3 mRNA levels, indicating a post-transcriptional regulation mechanism. PS1097 also inhibits BVDV-induced pathogenic effects in MDBK cells with an EC₅₀ of 1.3 μM and shows no significant cytotoxicity at concentrations up to 100 μM within three to four days post-viral infection. Furthermore, it effectively inhibits purified BVDV NS5B∆24 polymerase activity with an IC₅₀ of 0.64 μM.