Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus

Bassetto, Marcella ORCID: https://orcid.org/0000-0002-2491-5868, 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 and Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419 2013. Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus. Antiviral Research 98 (1) , pp. 12-18. 10.1016/j.antiviral.2013.01.002

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Abstract

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 and 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 and the US. In the present study, we report on the discovery of a novel series of compounds that inhibit CHIKV replication in the low μM 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 and 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 understanding of the CHIKV replication cycle and may represents a first step towards the development of a clinical candidate drug for the treatment of this disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Antiviral; Chikungunya; CHIKV; Homology model; Molecular dynamics; Virtual screening
Publisher:	Elsevier
ISSN:	0166-3542
Related URLs:	Publisher
Last Modified:	06 Jan 2024 05:12
URI:	https://orca.cardiff.ac.uk/id/eprint/45941

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