Hong Kong Med J 2014;20(Suppl 4):S22-5
Profiling of substrate-specificity and rational design of broad-spectrum peptidomimetic inhibitors for main proteases of coronaviruses
CP Chuck, ZH Ke, C Chen, DCC Wan, HF Chow, KB Wong
School of Life Sciences, The Chinese University of Hong Kong, Hong Kong
1. Substrate specificities of the main proteases from group 1, 2a, 2b, and 3 coronaviruses were comprehensively profiled at P5 to P3' positions.
2. Despite subtle differences in substrate specificities identified at P1, P2, and P4 positions, the main proteases from different strains of coronaviruses share many similarities, suggesting the feasibility of developing a broad-spectrum inhibitor.
3. 'Super-active' substrates with >4-fold increases in activity were created by combining multiple favourable substitutions.
4. Cbz-AVLQ-CN is a broad-spectrum inhibitor effective against six different strains of coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, IBV) with IC50 values of 1.3 to 4.6 µM.