Autor(es): Khan M, Dhanwani R, Patro I K, Rao P V L, Parida M M

Resumo: Inosine monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotide, namely, the conversion of IMP to XMP. The depletion of the intracellular GTP - dGTP pools is the major event occurring in the cells exposed to the inhibitors such as mycophenolic acid. The present study was undertaken with an objective to assess the antiviral potential of mycophenolic acid (MPA) against Chikungunya virus via inhibition of IMPDH enzyme in Vero cells. The inhibitory potential of MPA on CHIKV replication was assessed by virus inhibition assay (cytopathic effect, immunofluorescence), virus yield reduction assay - cell viability assay. Inhibition of virus induced apoptosis was analyzed by Hoechst staining, DNA fragmentation, immunoblotting of Caspase-3, PARP - Bcl-2. Percentage apoptotic cell population was determined by flow cytometry. Total genome infectivity was determined by analyzing the ratio of total infectious viral particles to the genome copy number. Non-toxic concentration of MPA (10 ?M) reduced ? 99.9% CHIKV titre in Vero cells. MPA via depletion of substrate for polymerase (GTP), inhibited CHIKV induced apoptosis. By limiting the rate of de novo synthesis of guanosine nucleotide, MPA could apparently block the formation of the CHIKV progeny. The antiviral activity of MPA against Chikungunya virus is mediated through depletion of GTP pool via inhibition of IMPDH as demonstrated by Immunoblotting - different microscopic analysis.

Palavras-Chave: Mycophenolic acid; Chikungunya; Virus inhibition; Apoptosis

Imprenta: Antiviral Research, v. 89, n. 1, p. 1-8, 2011

Identificador do objeto digital: 10.1016/j.antiviral.2010.10.009

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - DNA ; Chikungunya virus - Genome ; Chikungunya virus - Proteins ; Chikungunya Virus - Virus

Data de publicação: 2011