Autor(es): Bassetto Marcella, De Burghgraeve Tine, Delang Leen, Massarotti Alberto, Coluccia Antonio, Zonta Nicola, Gatti Valerio, Colombano Giampiero, Sorba Giovanni, Silvestri Romano, Tron Gian Cesare, Neyts Johan, Leyssen Pieter, Brancale Andrea

Resumo: Chikungunya virus (CHIKV) is an Arbovirus that is transmitted to humans primarily by the mosquito species Aedes aegypti. Infection with this pathogen is often associated with fever, rash - arthralgia. Neither a vaccine nor an antiviral drug is available for the prevention or treatment of this disease. Albeit considered a tropical pathogen, adaptation of the virus to the mosquito species Aedes albopictus, which is also very common in temperate zones, has resulted in recent outbreaks in Europe - the US. In the present study, we report on the discovery of a novel series of compounds that inhibit CHIKV replication in the low ?M range. In particular, we initially performed a virtual screening simulation of ?5 million compounds on the CHIKV nsP2, the viral protease, after which we investigated - explored the Structure-Activity Relationships of the hit identified in silico. Overall, a series of 26 compounds, including the original hit, was evaluated in a virus-cell-based CPE reduction assay. The study of such selective inhibitors will contribute to a better underst-ing of the CHIKV replication cycle - may represents a first step towards the development of a clinical c-idate drug for the treatment of this disease.

Palavras-Chave: Antiviral; Chikungunya; CHIKV; Homology model; Molecular dynamics; Virtual screening

Imprenta: Antiviral Research, v. 98, n. 1, p. 12-8, 2013

Identificador do objeto digital: 10.1016/j.antiviral.2013.01.002

Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever

Data de publicação: 2013