Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against chikungunya virus in vero cells
Identifieur interne : 000D50 ( Main/Exploration ); précédent : 000D49; suivant : 000D51Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against chikungunya virus in vero cells
Auteurs : Mohsin Khan [Inde] ; S. R. Santhosh [Inde] ; Mugdha Tiwari [Inde] ; P. V. Lakshmana Rao [Inde] ; Manmohan Parida [Inde]Source :
- Journal of Medical Virology [ 0146-6615 ] ; 2010-05.
English descriptors
- Teeft :
- Ammonium, Ammonium chloride, Assay, Cell viability, Cell viability assays, Chikungunya, Chikungunya virus, Chikv, Chikv infection, Chikv replication, Chloroquine, Chloroquine treatment, Clinical management, Concurrent treatment, Control cells, Current study, Curve analysis, Early stages, Genome, Genome copy number, Higher concentrations, Infection, Late stages, Online issue, Plaque, Replication, Ribavirin, Santhosh, Savarino, Selectivity index, Time course analysis, Treatment groups, Uorescence, Uorescence intensity, Uptake assay, Vero, Vero cells, Viral, Viral diseases, Viral infection, Viral inhibition, Virol, Virus infectivity, Virus internalization, Virus replication.
Abstract
The resurgence of Chikungunya virus (CHIKV) in the form of unprecedented and explosive epidemics in India and the Indian Ocean islands 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 and therapeutic effects of chloroquine on CHIKV replication in Vero cells were investigated. Inhibitory effects were observed when chloroquine was administered pre‐infection, post‐infection, and concurrent with infection, suggesting that chloroquine has prophylactic and 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, and cell viability assays. Chloroquine diminished CHIKV infection in a dose‐dependent manner, with an effective concentration range of 5–20 µM. Concurrent addition of drug with virus, or treatment of cells prior to infection drastically reduced virus infectivity and viral genome copy number by ≥99.99%. The maximum inhibitory effect of chloroquine was observed within 1–3 hr post‐infection (hpi), and 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 and/or endosomal acidification, based on a comparative evaluation using ammonium chloride, a known lysosomotropic agent. J. Med. Virol. 82: 817–824, 2010. © 2010 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/jmv.21663
Affiliations:
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Currently, there is no specific therapy available to treat CHIKV infection. In the present study, the in vitro prophylactic and therapeutic effects of chloroquine on CHIKV replication in Vero cells were investigated. Inhibitory effects were observed when chloroquine was administered pre‐infection, post‐infection, and concurrent with infection, suggesting that chloroquine has prophylactic and 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, and cell viability assays. Chloroquine diminished CHIKV infection in a dose‐dependent manner, with an effective concentration range of 5–20 µM. Concurrent addition of drug with virus, or treatment of cells prior to infection drastically reduced virus infectivity and viral genome copy number by ≥99.99%. The maximum inhibitory effect of chloroquine was observed within 1–3 hr post‐infection (hpi), and 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 and/or endosomal acidification, based on a comparative evaluation using ammonium chloride, a known lysosomotropic agent. J. Med. Virol. 82: 817–824, 2010. © 2010 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Inde</li></country></list><tree><country name="Inde"><noRegion><name sortKey="Khan, Mohsin" sort="Khan, Mohsin" uniqKey="Khan M" first="Mohsin" last="Khan">Mohsin Khan</name></noRegion><name sortKey="Lakshmana Rao, P V" sort="Lakshmana Rao, P V" uniqKey="Lakshmana Rao P" first="P. V." last="Lakshmana Rao">P. V. Lakshmana Rao</name><name sortKey="Parida, Manmohan" sort="Parida, Manmohan" uniqKey="Parida M" first="Manmohan" last="Parida">Manmohan Parida</name><name sortKey="Parida, Manmohan" sort="Parida, Manmohan" uniqKey="Parida M" first="Manmohan" last="Parida">Manmohan Parida</name><name sortKey="Santhosh, S R" sort="Santhosh, S R" uniqKey="Santhosh S" first="S. R." last="Santhosh">S. R. Santhosh</name><name sortKey="Tiwari, Mugdha" sort="Tiwari, Mugdha" uniqKey="Tiwari M" first="Mugdha" last="Tiwari">Mugdha Tiwari</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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