Enhancing the antiviral potency of ER α-glucosidase inhibitor IHVR-19029 against hemorrhagic fever viruses in vitro and in vivo

Publication date: Available online 15 December 2017 Source:Antiviral Research Author(s): Julia Ma, Xuexiang Zhang, Veronica Soloveva, Travis Warren, Fang Guo, Shuo Wu, Huagang Lu, Jia Guo, Qing Su, Helen Shen, Eric Solon, Mary Ann Comunale, Anand Mehta, Ju-Tao Guo, Sina Bavari, Yanming Du, Timothy M. Block, Jinhong Chang Targeting host functions essential for viral replication has been considered as a broad spectrum and resistance-refractory antiviral approach. However, only a few host functions have, thus far, been validated as broad-spectrum antiviral targets in vivo. ER α-glucosidases I and II have been demonstrated to be essential for the morphogenesis of many enveloped viruses, including members from four families of viruses causing hemorrhagic fever. In vivo antiviral efficacy of various iminosugar-based ER α-glucosidase inhibitors has been reported in animals infected with Dengue, Japanese encephalitis, Ebola, Marburg and influenza viruses. Herein, we established Huh7.5-derived cell lines with ER-α-glucosidase I or II knockout using CRISPR/Cas9 and demonstrated that the replication of Dengue, Yellow fever and Zika viruses was reduced by only 1–2 logs in the knockout cell lines. The results clearly indicate that only a partial suppression of viral replication can possibly be achieved with a complete inhibition of ER-α-glucosidases I or II by their inhibitors. We therefore explore to improve the antiviral efficacy of a lead iminosugar IHVR-19029...
Source: Antiviral Therapy - Category: Virology Source Type: research