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Zika virus (ZIKV) is a flavivirus that causes severe neuropathology in newborns and adults. There is no ZIKV-specific treatment or preventative. Therefore, it is urgent to develop safe and effective anti-ZIKV agents. Hemin, an iron-binding porphyrin, has been authorized by FDA to treat acute porphyria since the 1970s. Here, we aim to evaluate the anti-ZIKV effect of hemin in SNB-19 cells (a human glioma cell line) and explore the underlying mechanism based on the virus life cycle and functions of the host cell. Our study found that hemin has a strong activity to protect SNB-19 cells from ZIKV infection presented by decreased expression of viral proteins and virus yield. Meanwhile, ZIKV infection caused STAT1/IRF1 signaling activation and induced inflammatory responses in SNB-19 cells, which was relieved by hemin treatment. HO-1 has been reported to be potently induced by hemin and play a broad-spectrum antiviral effect. Intriguingly, hemin could still exert anti-ZIKV activity upon HO-1 siRNA treatment. Then, we conducted a time-of-addition assay, the result indicated hemin works mainly by interfering with the virus entry process. Further experiments excluded the effects of hemin on AXL-dependent viral adsorption and clathrin-mediated endocytosis processes. Subsequently, by fluorescence spectroscopy studies, intracellular fusion assay and syncytia formation assay, we revealed that hemin acts on the process of virus-endosome fusion. This study elaborated that hemin could play anti-ZIKV activity by disrupting the virus-endosome fusion process and shed new light on developing novel agents against ZIKV infection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B., (Copyright © 2015. Published by Elsevier B.V.)

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family. HBsAg, greatly outnumbered mature virion, has been mysterious since the discovery of HBV. A novel benzimidazole derivative, BM601, is identified inhibiting the secretion of HBV virions and HBsAg, with 50% effective concentration of 0.6μM and 1.5μM, as well as 50% cytotoxicity concentration of 24.5μM. It has no effect on transcription, protein production, nucleocapsid formation or intracellular HBV DNA synthesis. Immunofluorescence analysis suggests that BM601 might inhibit virion and HBsAg secretion by interfering surface protein aggregation in trans Golgi apparatus. Furthermore, BM601 does not trigger cellular stress response or affect HBeAg or host protein secretion. We hypothesize that BM601 is a secretion inhibitor functioning at the level of virion and HBsAg secretion pathway., (Copyright © 2014 Elsevier B.V. All rights reserved.)