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.
Highlights
Zika virus (ZIKV) belongs to the Flavivirus genus, which includes dengue virus (DENV), West Nile (WNV), yellow fever virus (YFV) and Japanese encephalitis viruses (JEV) and is mainly transmitted by Aedes mosquitoes, including Ae. aegypti and Ae. albopictus, in an urban cycle [1]
Our study provides a list of candidate agents for potential use to block ZIKV transmission in mosquitoes by chemical inhibition
We searched the literature for drugs and compounds that have been reported to exert antiZIKV and/or anti-DENV activity in mammalian or mosquito cells, using the following criteria: 1) significant inhibition of flavivirus (ZIKV or DENV) infection in mammalian or mosquito cells; 2) no obvious toxicity to the tested cells; 3) approval already granted for human use or clinical trials
Summary
Zika virus (ZIKV) belongs to the Flavivirus genus, which includes dengue virus (DENV), West Nile (WNV), yellow fever virus (YFV) and Japanese encephalitis viruses (JEV) and is mainly transmitted by Aedes mosquitoes, including Ae. aegypti and Ae. albopictus, in an urban cycle [1]. Control efforts to limit the population of Aedes mosquitoes and prevent mosquito biting rely mainly on insecticide application, removal of mosquito breeding sites, and the use of repellents and door/window curtains. These control methods are plagued by limitations such as insecticide resistance and logistics that hamper disease control, and novel control strategies are needed
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