Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening
作者： Chun-Yeung Lo , Olive Tin-Wai Li , Wen-Ping Tang , Chun Hu , Guo Xin Wang
DOI: 10.1038/S41598-018-20772-9
关键词:
摘要: Currently, many strains of influenza A virus have developed resistance against anti-influenza drugs, and it is essential to find new chemicals combat this virus. The polymerase with three proteins, PA, PB1 PB2, a crucial component the viral ribonucleoprotein (RNP) complex. Here, we report identification hit compound 221 by surface plasmon resonance (SPR) direct binding screening on C-terminal PA (PAC). Compound can subdue RNP activities attenuate replication. Its analogs were subsequently investigated twelve them could activities. One analogs, 312, impeded replication in Madin-Darby canine kidney cells IC50 27.0 ± 16.8 μM. In vitro interaction assays showed that 312 bound directly PAC Kd about 40 μM. Overall, novel PAC-targeting compounds provides ground for drug design future.
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