Autor(es): Khan Mohsin, Santhosh S R, Tiwari Mugdha, Lakshmana Rao P V, Parida Manmohan

Resumo: The resurgence of Chikungunya virus (CHIKV) in the form of unprecedented - explosive epidemics in India - the Indian Ocean isl-s after a gap of 32 years is a major public health concern. Currently, there is no specific therapy available to treat CHIKV infection. In the present study, the in vitro prophylactic - therapeutic effects of chloroquine on CHIKV replication in Vero cells were investigated. Inhibitory effects were observed when chloroquine was administered pre-infection, post-infection, - concurrent with infection, suggesting that chloroquine has prophylactic - therapeutic potential. The inhibitory effects were confirmed by performing a plaque reduction neutralization test (PRNT), real-time reverse transcriptase (RT)-PCR analysis of viral RNA levels, - cell viability assays. Chloroquine diminished CHIKV infection in a dose-dependent manner, with an effective concentration range of 5-20 microM. Concurrent addition of drug with virus, or treatment of cells prior to infection drastically reduced virus infectivity - viral genome copy number by >/=99.99%. The maximum inhibitory effect of chloroquine was observed within 1-3 hr post-infection (hpi), - treatment was ineffective once the virus successfully passed through the early stages of infection. The mechanism of inhibition of virus activity by chloroquine involved impaired endosomal-mediated virus entry during early stages of virus replication, most likely through the prevention of endocytosis -/or endosomal acidification, based on a comparative evaluation using ammonium chloride, a known lysosomotropic agent.

Imprenta: Journal of Medical Virology, v. 82, n. 5, p. 817-824, 2010

Identificador do objeto digital: 10.1002/jmv.21663

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Genome ; Chikungunya virus - RNA ; Chikungunya virus - Real Time PCR ; Chikungunya virus - RT-PCR ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemic ; Chikungunya virus - Public health

Data de publicação: 2010