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Antiviral Drug Discovery Targeting Zika Virus Protease

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Technical Report,15 Jul 2018,14 Jul 2019

Corporate Author:

Baylor College of Medicine Houston United States

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Zika virus, transmitted primarily by mosquitos, could become endemic in the tropical and subtropical regions including the southern states and territories of the United States. It could cause catastrophic consequences to the public health, such as microcephaly small brainhead of newborns. However, there are no antiviral drugs or vaccines for Zika infection. Zika virus protease ZVpro is a viral protein that is essential for viral replication. ZVpro is therefore a drug target. The overall goal of this project is to use a combination of rational inhibitor design, medicinal chemistry, X-ray crystallography and antiviral activity testing to discover small-molecule inhibitors of ZVpro, which are potential drug candidates for Zika infection. During the first funding period, the overall progress for the project is satisfactory and in line with what we proposed. Approx. 120 potential inhibitors have been designed and synthesized, among which a number of compounds showed potent to good inhibitory activities against ZVpro with IC50 values of 0.2-10 micrometers. Methods for other biochemical, X-ray crystallography, and biological activity assays have been developed. Testing of the activities of the synthesized compounds are currently on-going.

Subject Categories:

  • Pharmacology
  • Microbiology

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