Autor(es): Staveness Daryl, Abdelnabi Rana, Near Katherine E, Nakagawa Yu, Neyts Johan, Delang Leen, Leyssen Pieter, Wender Paul A

Resumo: Chikungunya virus (CHIKV) has been spreading rapidly, with over one million confirmed or suspected cases in the Americas since late 2013. Infection with CHIKV causes devastating arthritic - arthralgic symptoms. Currently, there is no therapy to treat this disease, - the only medications focus on relief of symptoms. Recently, protein kinase C (PKC) modulators have been reported to inhibit CHIKV-induced cell death in cell assays. The salicylate-derived bryostatin analogues described here are structurally simplified PKC modulators that are more synthetically accessible than the natural product bryostatin 1, a PKC modulator - clinical lead for the treatment of cancer, Alzheimer's disease, - HIV eradication. Evaluation of the anti-CHIKV activity of these salicylate-derived bryostatin analogues in cell culture indicates that they are among the most potent cell-protective agents reported to date. Given that they are more accessible - significantly more active than the parent natural product, they represent new therapeutic leads for controlling CHIKV infection. Significantly, these analogues also provide evidence for the involvement of a PKC-independent pathway. This adds a fundamentally distinct aspect to the importance or involvement of PKC modulation in inhibition of chikungunya virus replication, a topic of recent - growing interest.

Imprenta: Journal of Natural Products, v. 79, n. 4, p. 680-684, 2016

Identificador do objeto digital: 10.1021/acs.jnatprod.5b01017

Descritores: Chikungunya virus - Cell ; Chikungunya Virus - Virus ; Chikungunya virus - Immunology

Data de publicação: 2016

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