Flavivirus Entry Inhibitors.

Flaviviruses, including Dengue virus, Zika virus, Yellow fever virus, Japanese encephalitis virus, West Nile virus, cause thousands of deaths and millions of illnesses each year. The large outbreak of ZIKV in 2016 reminds us that flaviviruses can pose a serious threat to human safety and public health as emerging and re-emerging viruses. However, there are no specific drugs approved for the treatment of flavivirus infections. Due to no need to enter the cells, viral entry inhibitors have the unique advantage in suppressing viral infections. Flaviviruses bind to receptors and attach to the cell surface, then enter the endosome in a clathrin-dependent manner and finalizes the viral entry process after fusion with the cell membrane in a low pH environment. Small molecules, antibodies or peptides can inhibit flavivirus entry by targeting the above processes. Here, we focus on flavivirus entry inhibitors with well-defined target and antiviral activity. We hope that our review will provide a theoretical basis for flavivirus treatment and drug research and help to accelerate the clinical application of flavivirus entry inhibitors.