Expression and biochemical characterization of nsP2 cysteine protease of Chikungunya virus
Autor(es): Pastorino Boris A M, Peyrefitte Christophe N, Almeras Lionel, Grandadam Marc, Rolland Dominique, Tolou Hugues J, Bessaud Maël
Resumo: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes epidemic fever, rash - polyarthralgia in Africa - Asia. Although it is known since the 1950s, new epidemiological - clinical features reported during the recent outbreak in the Indian Ocean can be regarded as the emergence of a new disease. Numerous severe forms of the infection have been described that put emphasis on the lack of efficient antiviral therapy. Among the virus-encoded enzymes, nsP2 constitutes an attractive target for the development of antiviral drugs. It is a multifunctional protein of approximately 90 kDa with a helicase motif in the N-terminal portion of the protein while the papain-like protease activity resides in the C-terminal portion. The nsP2 proteinase is an essential enzyme whose proteolytic activity is critical for virus replication. In this work, a recombinant CHIKV nsP2pro - a C-terminally truncated variant were expressed in Escherichia coli - purified by metal-chelate chromatography. The enzymatic properties of the proteinase were then determined using specific synthetic fluorogenic substrates. This study constitutes the first characterization of a recombinant CHIKV nsP2 cysteine protease, which may be useful for future drug screening.
Palavras-Chave: Alphavirus; Chikungunya virus; nsP2; Papain-like protease; Protease inhibitors; Viral cysteine protease
Imprenta: Virus Research, v. 131, n. 2, p. 293-298, 2008
Identificador do objeto digital: 10.1016/j.virusres.2007.09.009
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic
Data de publicação: 2008
