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Inhibition of enterovirus 71 replication by an α-hydroxy-nitrile derivative NK-1.9k.
- Source :
-
Antiviral Research . May2017, Vol. 141, p91-100. 10p. - Publication Year :
- 2017
-
Abstract
- Enterovirus 71 (EV71) is one of the major etiological agents of human hand-foot-and-mouth disease (HFMD) worldwide. EV71 infection in young children and people with immunodeficiency causes severe symptoms with a high fatality rates. However, there is still no approved drugs to treat such infections. Based on our previous report of a peptide-aldehyde anti-EV71 protease, we present here a highly specific α-hydroxy-nitrile derivative NK-1.9k, which inhibited the proliferation of multiple EV71 strains and coxsackievirus A16 (CVA16) in various cells with EC 50 of 37.0 nM with low cytotoxicity (CC 50 > 200 μM). The hydroxy-nitrile covalent warhead conferred NK-1.9k high potency and selectivity to interact with the cysteine residue of the active site of the viral protease. We also documented the resistance to NK-1.9k with a N69S mutation in EV71 3C pro . The combination of NK-1.9k and EV71 polymerase or entry inhibitors produced strong synergistic antiviral effects. Collectively, our findings suggest our compounds can potentially be developed as drugs for the treatment of HFMD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01663542
- Volume :
- 141
- Database :
- Academic Search Index
- Journal :
- Antiviral Research
- Publication Type :
- Academic Journal
- Accession number :
- 121972357
- Full Text :
- https://doi.org/10.1016/j.antiviral.2017.01.002