bims-antpol 2024-12-29 papers

Issue of 2024–12–29
two papers selected by
Rick Sheridan, EMSKE Phytochem

Antiviral Res. 2024 Dec 21. pii: S0166-3542(24)00284-5. [Epub ahead of print] 106073

Antiviral effect of pinostrobin, a bioactive constituent of Boesenbergia rotunda, against porcine epidemic diarrhea virus.

Nopporn Chutiwitoonchai, Radeekorn Akkarawongsapat, Suphat Chantawarin, Chutima Jiarpinitnun, Benjamas Liwnaree, Samaporn Teeravechyan, Sunhapas Soodvilai.

Global swine industry has long been severely affected by the periodic outbreaks of porcine epidemic diarrhea (PED), a deadly infectious disease in piglets caused by the porcine epidemic diarrhea virus (PEDV). Currently, available vaccines and antiviral drugs could not provide effective prevention and treatment of PEDV infection in pigs. In this study, Boesenbergia rotunda (B. rotunda) extract and its major bioactive flavonoid, pinostrobin, were demonstrated to exhibit remarkable anti-PEDV activities with EC50 values of 0.33 ± 0.02 μg/ml and 2.71 ± 0.12 μM, and selectivity indices (SI) of 11.93 and >184.55, respectively. Results based on a time-of-addition assay showed that pinostrobin blocked PEDV infection mainly at the early stages of infection. More specifically, pinostrobin reduced cell-cell fusion mediated by the viral spike protein, suggesting that the compound may target the virus fusion step. We also synthesized pinostrobin derivatives and explored the impact of pinostrobin structural features to the observed anti-PEDV activity. Results indicated the importance of the hydroxyl group and substituent on the phenyl ring. In summary, this study highlights the potential of B. rotunda extract and its bioactive compound, pinostrobin, as candidates for the development of antiviral drugs to more effectively control PEDV infection.

Keywords: Boesenbergia rotunda extract; antiviral; pinostrobin; porcine epidemic diarrhea virus

DOI: https://doi.org/10.1016/j.antiviral.2024.106073

RSC Med Chem. 2024 Dec 23.

Targeting host integrated stress response: lead discovery of flavonoid compounds active against coronaviruses PEDV and PDCoV.

Liang Yi, Yishuai Wang, Jiehuang Wang, Yihan Chen, Weixue Huang, Ying Liao, Qingwen Zhang.

Viral infections trigger the integrated stress response (ISR) in eukaryotic cells that leads to the activation of eIF2α kinases, the elevation of eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, and thereby the shutdown of global protein synthesis that viruses rely on to replicate. Coronaviruses and other viruses have evolved various subversion mechanisms to counteract the antiviral ISR. These intricate host-virus interactions may be exploited by pharmacologically activating the host ISR for the development of host-directed antivirals (HDAs), an increasingly relevant area of research. In this study, we have discovered a new class of flavonoid-based ISR activators that exhibit potent antiviral activity against porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV). PEDV and PDCoV are animal coronaviruses of great veterinary and economic importance, for which there are currently no effective therapeutics. The mechanistic study indicated that lead compounds 1-B and 1-C inhibit PEDV and PDCoV replication via upregulating eIF2α phosphorylation and thereby downregulating global protein synthesis in host cells, suggesting they are HDA antivirals.

DOI: https://doi.org/10.1039/d4md00846d