Influenza A virus has caused a wide spreading pandemic in the past century. The four serious pandemics including "the 1968 Hong Kong flu", has caused millions of deaths around the world. In this case, antiviral inhibitor discovery has gradually been considered as a promising way of treating influenza A virus epidemics. The most commonly used antiviral inhibitors in public are M2 proton channel inhibitors and neuraminidase inhibitors. But both target proteins protrude on the surface of viral capsid, their conformational changes can lead to the unbinding of inhibitors, and further to the resistance to these inhibitors. Therefore, we have discovered some potential molecular inhibitors to the treatment of influenza A virus. To have a high-throughput screening efficiency and bette...[ Read more ]

Influenza A virus has caused a wide spreading pandemic in the past century. The four serious pandemics including "the 1968 Hong Kong flu", has caused millions of deaths around the world. In this case, antiviral inhibitor discovery has gradually been considered as a promising way of treating influenza A virus epidemics. The most commonly used antiviral inhibitors in public are M2 proton channel inhibitors and neuraminidase inhibitors. But both target proteins protrude on the surface of viral capsid, their conformational changes can lead to the unbinding of inhibitors, and further to the resistance to these inhibitors. Therefore, we have discovered some potential molecular inhibitors to the treatment of influenza A virus. To have a high-throughput screening efficiency and better inhibitor potency such as permeability and solubility, small molecules with potential antiviral effect due to the literature were chosen. To reduce the structural changes effect by genetic variation, we choose a more functional enzyme of influenza A virus with more conserved sequence as the target receptor: influenza A virus polymerase. To test and select potential candidate inhibitors from small molecular compounds library, viral polymerase was expressed in vitro and the inhibitor screening experiment was done. In addition, we used computational simulation method to explore the binding modes between identified inhibitors and influenza A virus polymerase. In particular, the molecular docking method was applied, which could rank multiple binding modes by factors as binding affinity and number of hydrogen bonds. There are some positive potential candidates selected from inhibitor screening experiment, which have limited cytotoxicity value and sufficient inhibitive value from the testing of LDH cytotoxicity assay and luciferase assay, respectively. These identified small molecular compounds hold potential to be further developed as inhibitors against influenza A virus. In the future, we plan to further elucidate the molecular mechanisms of these inhibitors binding to virus polymerase via the combination of experimental and simulation approaches.