2. Academic Validation
  3. Identification of Inhibitors of ZIKV Replication

Identification of Inhibitors of ZIKV Replication

  • Viruses. 2020 Sep 18;12(9):1041. doi: 10.3390/v12091041.
Desarey Morales Vasquez 1 2 3,  Jun-Gyu Park 2 3,  Ginés Ávila-Pérez 2,  Aitor Nogales 2,  Juan Carlos de la Torre 4,  Fernando Almazan 5,  Luis Martinez-Sobrido 2 3
Affiliations

Affiliations

  • 1 Clinical and Translational Science Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14625, USA.
  • 2 Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14625, USA.
  • 3 Department of Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
  • 4 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • 5 Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-11 CSIC), Universidad Autonόma de Madrid, 28049 Madrid, Spain.
PMID: 32961956 DOI: 10.3390/v12091041
Abstract

Zika virus (ZIKV) was identified in 1947 in the Zika forest of Uganda and it has emerged recently as a global health threat, with recurring outbreaks and its associations with congenital microcephaly through maternal fetal transmission and Guillain-Barré syndrome. Currently, there are no United States (US) Food and Drug Administration (FDA)-approved vaccines or antivirals to treat ZIKV infections, which underscores an urgent medical need for the development of disease intervention strategies to treat ZIKV Infection and associated disease. Drug repurposing offers various advantages over developing an entirely new drug by significantly reducing the timeline and resources required to advance a candidate Antiviral into the clinic. Screening the ReFRAME library, we identified ten compounds with Antiviral activity against the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV). Moreover, we showed the ability of these ten compounds to inhibit influenza A and B virus infections, supporting their broad-spectrum Antiviral activity. In this study, we further evaluated the broad-spectrum Antiviral activity of the ten identified compounds by testing their activity against ZIKV. Among the ten compounds, Azaribine (SI-MTT = 146.29), AVN-944 (SI-MTT = 278.16), and Brequinar (SI-MTT = 157.42) showed potent anti-ZIKV activity in post-treatment therapeutic conditions. We also observed potent anti-ZIKV activity for Mycophenolate mofetil (SI-MTT = 20.51), Mycophenolic acid (SI-MTT = 36.33), and AVN-944 (SI-MTT = 24.51) in pre-treatment prophylactic conditions and potent co-treatment inhibitory activity for Obatoclax (SI-MTT = 60.58), Azaribine (SI-MTT = 91.51), and Mycophenolate mofetil (SI-MTT = 73.26) in co-treatment conditions. Importantly, the inhibitory effect of these compounds was strain independent, as they similarly inhibited ZIKV strains from both African and Asian/American lineages. Our results support the broad-spectrum Antiviral activity of these ten compounds and suggest their use for the development of Antiviral treatment options of ZIKV Infection.

Keywords

ReFRAME library; Zika virus; antivirals; drug repurposing; drug treatment; flavivirus; therapeutic.

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