Abstract

Article info 2015 3 (3)    003  (03)   pp.  131 ~ 137
Title Identification of lead inhibitors targeting influenza A virus nucleoprotein through surface plasmon resonance screening
Authors Chun-Yeung Lo1, Sze-Ting Choi1, Olive Tin-Wai Li2, Jacky Chi-Ki Ngo1, David Chi-Cheong Wan3, Leo Lit-Man Poon2 and Pang-Chui Shaw1*
Institutions 1Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China, 2Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, 3School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. *Correspondence: pcshaw@cuhk.edu.hk
Abstract Currently, many strains of influenza A virus have developed resistance against anti-influenza drugs, and it is essential to find new chemicals to combat this virus. The viral nucleoprotein (NP) is a major component of the ribonucleoprotein (RNP) complex for the transcription and replication of the virus. In this study, we have employed surface plasmon resonance direct binding screening on the influenza A NP and found a hit compound 16 that can subdue influenza RNP activities. Subsequently, two analogs (compounds 55 & 58) from compound 16 were identified which inhibit RNP activities of various influenza A subtypes and viral growth at micromolar levels. These analogs were also shown to directly interact with NP, with KD 12.0±1.25 and 41.6±1.93 μM respectively by surface plasmon resonance assay.