Autor(es): Albulescu Irina C, van Hoolwerff Marcella, Wolters Laura A, Bottaro Elisabetta, Nastruzzi Claudio, Yang Shih Chi, Tsay Shwu-Chen, Hwu Jih Ru, Snijder Eric J, van Hemert Martijn J

Resumo: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe - often persistent arthritis. In recent years, millions of people have been infected with this virus for which registered antivirals are still lacking. Using our recently established in vitro assay, we discovered that the approved anti-parasitic drug suramin inhibits CHIKV RNA synthesis (IC50 of ?5?M). The compound inhibited replication of various CHIKV isolates in cell culture with an EC50 of ?80?M (CC50>5mM) - was also active against Sindbis virus - Semliki Forest virus. In vitro studies hinted that suramin interferes with (re)initiation of RNA synthesis, whereas time-of-addition studies suggested it to also interfere with a post-attachment early step in infection, possibly entry. CHIKV (nsP4) mutants resistant against favipiravir or ribavirin, which target the viral RNA polymerase, did not exhibit cross-resistance to suramin, suggesting a different mode of action. The assessment of the activity of a variety of suramin-related compounds in cell culture - the in vitro assay for RNA synthesis provided more insight into the moieties required for antiviral activity. The antiviral effect of suramin-containing liposomes was also analyzed. Its approved status makes it worthwhile to explore the use of suramin to prevent -/or treat CHIKV infections.

Palavras-Chave: Alphavirus; Chikungunya virus; Entry; Inhibitor; RNA synthesis; Suramin

Imprenta: Antiviral Research, v. 121, p. 39-46, 2015

Identificador do objeto digital: 10.1016/j.antiviral.2015.06.013

Descritores: Chikungunya virus - Cell ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus

Data de publicação: 2015

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