Antiviral Activity of Nordihydroguaiaretic Acid and Its Derivative Tetra-O-Methyl Nordihydroguaiaretic Acid against West Nile Virus and Zika Virus.
Antimicrob Agents Chemother
; 61(8)2017 08.
Article
em En
| MEDLINE
| ID: mdl-28507114
ABSTRACT
Flaviviruses are positive-strand RNA viruses distributed all over the world that infect millions of people every year and for which no specific antiviral agents have been approved. These viruses include the mosquito-borne West Nile virus (WNV), which is responsible for outbreaks of meningitis and encephalitis. Considering that nordihydroguaiaretic acid (NDGA) has been previously shown to inhibit the multiplication of the related dengue virus and hepatitis C virus, we have evaluated the effect of NDGA, and its methylated derivative tetra-O-methyl nordihydroguaiaretic acid (M4N), on the infection of WNV. Both compounds inhibited the infection of WNV, likely by impairing viral replication. Since flavivirus multiplication is highly dependent on host cell lipid metabolism, the antiviral effect of NDGA has been previously related to its ability to disturb the lipid metabolism, probably by interfering with the sterol regulatory element-binding proteins (SREBP) pathway. Remarkably, we observed that other structurally unrelated inhibitors of the SREBP pathway, such as PF-429242 and fatostatin, also reduced WNV multiplication, supporting that the SREBP pathway may constitute a druggable target suitable for antiviral intervention against flavivirus infection. Moreover, treatment with NDGA, M4N, PF-429242, and fatostatin also inhibited the multiplication of the mosquito-borne flavivirus Zika virus (ZIKV), which has been recently associated with birth defects (microcephaly) and neurological disorders. Our results point to SREBP inhibitors, such as NDGA and M4N, as potential candidates for further antiviral development against medically relevant flaviviruses.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
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3_ND
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4_TD
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Febre do Nilo Ocidental
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Vírus do Nilo Ocidental
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Masoprocol
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Zika virus
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Infecção por Zika virus
Limite:
Animals
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Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2017
Tipo de documento:
Article