Identification of novel small-molecule inhibitors of Zika virus infection

Ewa D Micewicz; Ronik Khachatoorian; Samuel W French; Piotr Ruchala

doi:10.1016/j.bmcl.2017.12.019

Identification of novel small-molecule inhibitors of Zika virus infection

Bioorg Med Chem Lett. 2018 Feb 1;28(3):452-458. doi: 10.1016/j.bmcl.2017.12.019. Epub 2017 Dec 9.

Authors

Ewa D Micewicz¹, Ronik Khachatoorian², Samuel W French³, Piotr Ruchala⁴

Affiliations

¹ Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
² Department of Pathology and Laboratory Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
³ Department of Pathology and Laboratory Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA; UCLA AIDS Institute, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
⁴ Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, USA; The Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA 90024, USA. Electronic address: [email protected].

PMID: 29258771
DOI: 10.1016/j.bmcl.2017.12.019

Abstract

The recent re-emergence of Zika virus (ZIKV), a member of the Flaviviridae family, has become a global emergency and a serious public health threat worldwide. ZIKV infection causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women causing various developmental abnormalities. Currently, there are no effective methods of preventing or treating ZIKV infection, and new treatment options are urgently needed. Therefore, we have used an in vitro plaque assay to screen a limited proprietary library of small organic compounds and identified highly bioactive leads, with the most active analogs showing activity in low picomolar range. Identified "hits" possess certain common structural features that can be used in the design of the next generation(s) of ZIKV inhibitors. Collectively, our findings suggest that identified compounds represent excellent template(s) for the development of inexpensive and orally available anti-Zika drugs.

Keywords: Antivirals; Plaque assay; Screening; Zika inhibitors; Zika virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Cell Survival / drug effects
Dose-Response Relationship, Drug
Humans
Molecular Structure
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship
Zika Virus / drug effects*
Zika Virus Infection / drug therapy*

Substances

Antiviral Agents
Small Molecule Libraries