Identification of anti-flaviviral drugs with mosquitocidal and anti-Zika virus activity in Aedes aegypti

Shengzhang Dong, Seokyoung Kang, George Dimopoulos

Research output: Contribution to journalArticle

Abstract

Zika virus (ZIKV), an emerging arbovirus belonging to the genus Flavivirus, is transmitted by Aedes mosquitoes. ZIKV infection can cause microcephaly of newborn babies and Guillain-Barré syndrome in adults. Because no licensed vaccine or specific antiviral treatment is available for ZIKV infection, the most commonly used approach to control the spread of ZIKV is suppression of the mosquito vector population. A novel proposed strategy to block arthropod virus (arbovirus) transmission is based on the chemical inhibition of virus infection in mosquitoes. However, only a few drugs and compounds have been tested with such properties. Here we present a comprehensive screen of 55 FDA-approved anti-flaviviral drugs for potential anti-ZIKV and mosquitocidal activity. Four drugs (auranofin, actinomycin D (Act-D), bortezomib and gemcitabine) were toxic to C6/36 cells, and two drugs (5-fluorouracil and mycophenolic acid (MPA)) significantly reduced ZIKV production in C6/36 cells at 2 μM and 0.5 μM, respectively. Three drugs (Act-D, cyclosporin A, ivermectin) exhibited a strong adulticidal activity, and six drugs (U18666A, retinoic acid p-hydroxyanilide (4-HPR), clotrimazole, bortezomib, MPA, imatinib mesylate) significantly suppressed ZIKV infection in mosquito midguts. Some of these FDA-approved drugs may have potential for use for the development of ZIKV transmission-blocking strategies.

Original languageEnglish (US)
Pages (from-to)e0007681
JournalPLoS neglected tropical diseases
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2019

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Aedes
Pharmaceutical Preparations
Culicidae
Mycophenolic Acid
Arboviruses
Dactinomycin
gemcitabine
Fenretinide
Auranofin
Clotrimazole
Flavivirus
Ivermectin
Microcephaly
Arthropods
Poisons
Virus Diseases
Tretinoin
Zika Virus
Fluorouracil
Cyclosporine

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Identification of anti-flaviviral drugs with mosquitocidal and anti-Zika virus activity in Aedes aegypti. / Dong, Shengzhang; Kang, Seokyoung; Dimopoulos, George.

In: PLoS neglected tropical diseases, Vol. 13, No. 8, 01.08.2019, p. e0007681.

Research output: Contribution to journalArticle

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