Journal
ANTIVIRAL RESEARCH
Volume 141, Issue -, Pages 29-37Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2017.02.002
Keywords
Zika; Antiviral; Treatment; Protease; Bromocriptine; Interferon
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Funding
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases of the Department of Health
- Emerging Arbovirus Research fund
- Food and Health Bureau
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
- Ministry of Education of China
- Government of the Hong Kong Special Administrative Region
- Hong Kong Special Administrative Region
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Zika virus (ZIKV) infection is associated with congenital malformations in infected fetuses and severe neurological and other systemic complications in adults. There are currently limited anti-ZIKV treatment options that are readily available and safe for use in pregnancy. In this drug repurposing study, bromocriptine was found to have inhibitory effects on ZIKV replication in cytopathic effect inhibition, virus yield reduction, and plaque reduction assays. Time-of-drug-addition assay showed that bromocriptine exerted anti-ZIKV activity between 0 and 12 h post-ZIKV inoculation, corroborating with post entry events in the virus replication cycle prior to budding. Our docking model showed that bromocriptine interacted with several active site residues of the proteolytic cavity involving 1-151 and S135 in the ZIKV-NS2B-NS3 protease protein, and might occupy the active site and inhibit the protease activity of the ZIKV-NS2B-NS3 protein. A fluorescence-based protease inhibition assay confirmed that bromocriptine inhibited ZIKV protease activity. Moreover, bromocriptine exhibited synergistic effect with interferon -cab against ZIKV replication in cytopathic effect inhibition assay. The availability of per vagina administration of bromocriptine as suppositories or vaginoadhesive discs and the synergistic anti-ZIKV activity between bromocriptine and type I interferon may make bromocriptine a potentially useful and readily available treatment option for ZIKV infection. The anti-ZIKV effects of bromocriptine should be evaluated in a suitable animal model. (C) 2017 Elsevier B.V. All rights reserved.
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