Search

The chikungunya virus (CHIKV) is a mosquito-borne virus that belongs to the genus Alphavirus, family Togaviridae. It is the cause of chikungunya fever in humans, which presents a serious global threat due to its high rate of contagion. The clinical symptoms of CHIKV include fever and persistent, severe arthritis. Micafungin has broad-spectrum fungicidal activity against Candida spp. is a promising echinocandin that was recently approved by the U.S. Food and Drug Administration (FDA) and has demonstrated activity against Candida and Aspergillus. Recent studies have demonstrated the antiviral activity of micafungin; however, the inhibitory effects against CHIKV have yet to be investigated. Our objectives in this study were to explore the antiviral effects of micafungin on CHIKV infection and to elucidate the potential molecular mechanisms of inhibition. We determined that micafungin has the ability to counter CHIKV-induced cytopathic effects. We further discovered that micafungin limits virus replication, release, cell-to-cell transmission, and also slightly affected virus stability during high doses treatment. The efficacy of micafungin was further confirmed against two clinical isolates of CHIKV and two alphaviruses: Sindbis virus (SINV) and Semliki Forest virus (SFV). Our findings suggest that micafungin has considerable potential as a novel inhibitor against the viral replication, and intracellular and extracellular transmission of CHIKV, and has a little effect on virus stability. Our findings also suggest that micafungin could have curative effects on other alphavirus infections.

Zika virus (ZIKV) has been the cause of some epidemics since 2007. The correlations of microcephaly and Guillain–Barre syndrome with ZIKV have been noticed. Unfortunately, researchers have yet to develop an effective vaccine or drug approved for ZIKV infection. Anidulafungin is a member of echinocandins that is used to treat candida infections. This study assessed the antiviral capability of anidulafungin against ZIKV. Anidulafungin was shown to significantly decrease viral RNA levels, protein expression levels, viral yields, and the rate of infection. In time of addition assays, anidulafungin exhibited inhibitory activities in the early stages of ZIKV infection. In binding and entry assays, administering anidulafungin did not lead to a corresponding decrease in quantity of viral RNA, but a significant decrease in ZIKV infectivity was observed in virucidal assays. This indicated that anidulafungin interferes directly with virions. T-1105 is a viral polymerase inhibitor, which functions in the late stage of ZIKV infection. When anidulafungin was administered in combination with T-1105, an obvious synergistic effect was observed, resulting in a combination index (CI) value of 0.85 ± 0.13. Finally, we evaluated the effects of echinocandins in terms of half-maximal inhibitory concentration (IC50), calculation of cytotoxicity concentration 50% (CC50), selectivity index (SI), and Patchdock score. Among the tests, anidulafungin bears the lowest IC50 and highest Patchdock score. Although anidulafungin is classified as a pregnancy category C agent; however, combination therapy of anidulafungin with a viral RNA replication inhibitor could expand treatment options for ZIKV infection.