Biochemical Screening of Potent Zika Virus Protease Inhibitors |
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| Authors: | Camila Coelho Dr Gloria Gallo Dr Leon Hardy Dr Maria Elena Bottazzi Dr Claudia Campos Dr Martin Würtele |
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| Affiliation: | 1. Department of Science and Technology, Federal University of São Paulo, 330 Talim, 12231-280 São José dos Campos, Brazil;2. Department of Physics, University of South Florida, 4202 East Fowler Avenue, FL 33620-7100 Tampa, USA;3. Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, 1102 Bates, TX 77030 Houston, USA |
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| Abstract: | As the Zika virus protease is an essential and well-established target for the development of antiviral agents, we biochemically screened for inhibitors using a purified recombinantly expressed form of this enzyme. As a result, we were able to identify 10 new Zika virus protease inhibitors. These compounds are natural products and showed strong inhibition in the biochemical assays. Inhibitory constants values for the compounds ranged from 5 nM to 8 μM. Among the most potent inhibitors are flavonoids like irigenol hexa-acetate (Ki=0.28 μM), katacine (Ki=0.26 μM), theaflavin gallate (Ki=0.40 μM) and hematein (Ki=0.33 μM). Inhibitors from other groups of natural products include sennoside A (Ki=0.19 μM) and gossypol (Ki=0.70 μM). Several of the obtained compounds are known for their beneficial health effects and have acceptable pharmacokinetic characteristics. Thus, they could be of interest as lead compounds for the development of important and essential Zika antiviral drugs. |
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| Keywords: | Biochemical screening proteases Zika viruses drug discovery |
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