Autor(es): Staveness Daryl, Abdelnabi Rana, Schrier Adam J, Loy Brian A, Verma Vishal A, DeChristopher Brian A, Near Katherine E, Neyts Johan, Delang Leen, Leyssen Pieter, Wender Paul A

Resumo: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus showing a recent resurgence - rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the-counter (OTC) analgesics, which alleviate the devastating arthritic - arthralgic symptoms. To identify novel inhibitors of the virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer's disease, - HIV eradication, were investigated for in vitro antiviral activity - were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts - even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- - B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PKC modulator, is inactive in these assays. These new findings indicate that the observed anti-CHIKV activity is not solely mediated by PKC modulation, suggesting possible as yet unidentified targets for CHIKV therapeutic intervention. The high potency - low toxicity of these bryologs make them promising new leads for the development of a CHIKV treatment.

Imprenta: Journal of Natural Products v. 79, n. 4, p. 675-679, 2016

Identificador do objeto digital: 10.1021/acs.jnatprod.5b01016

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

Data de publicação: 2016

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