Inhibition of dengue virus production and cytokine/chemokine expression by ribavirin and compound A

Rattanaburee, Thidarath; Junking, Mutita; Panya, Aussara; Sawasdee, Nunghathai; Songprakhon, Pucharee; Suttitheptumrong, Aroonroong; Limjindaporn, Thawornchai; Haegeman, Guy; Yenchitsomanus, Pa‐thai

doi:10.1016/j.antiviral.2015.10.005

Cited by 30 publications

(21 citation statements)

References 48 publications

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“…Ribavirin, whose safety has already been demonstrated, is widely used as a therapeutic drug for hepatitis C. Because ribavirin inhibits viral RNA-dependent RNA polymerases (Bougie and Bisaillon, 2003;Maag et al, 2001;Toltzis et al, 1988) and mRNA cap formation (Goswami et al, 1979). Indeed, ribavirin could inhibit the replication of DENV, Middle East respiratory syndrome (MERS) coronavirus, and severe acute respiratory syndrome (SARS) coronavirus (Falzarano et al, 2013a(Falzarano et al, , 2013bRattanaburee et al, 2015;Koren et al, 2003), which suggests that ribavirin could be effective against RNA viruses. Thus, it is reasonable to predict that ribavirin could also suppress the replication of ZIKV, which is a single-stranded positive-sense RNA virus.…”

Section: Discussionmentioning

confidence: 99%

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Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice

et al. 2017

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Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-β (IFN-β), on ZIKV replication. In mammalian cells, we observed an inhibitory effect of ribavirin on ZIKV replication and ZIKV-induced cell death without cytotoxic effect. Furthermore, we found that STAT1-deficient mice, which lack type I IFN signaling, were highly sensitive to ZIKV infection and exhibited lethal outcome. Ribavirin abrogated viremia in ZIKV-infected STAT-1-deficient mice. These data suggest that the inhibition of viral RNA-dependent RNA polymerases may be effective for treatment of ZIKV infection. Our data provide a new insight into the mechanisms for inhibition of ZIKV replication and prevention of Zika fever.

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Section: Discussionmentioning

confidence: 99%

“…Like ZIKV and DENV, HCV is a member of family Flaviviridae. Recent work showed that ribavirin inhibited DENV replication in Vero cells (Rattanaburee et al, 2015), suggesting that the drug might also be an effective inhibitor of ZIKV replication.…”

Section: Introductionmentioning

confidence: 99%

Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice

et al. 2017

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“…Increased expression of RANTES is observed in intra-cerebral inoculation of DENV, which induces behavioral changes and encephalitis in C57BL/6 mice. Both RANTES and IP-10 were shown to be induced in human lung epithelial carcinoma cells (A549) infected with DENV [ 100 ]. Our research group also found similar results in DENV-infected HEK 293 cells and reported this is by NF-kB activation [ 101 ].…”

Section: Discussionmentioning

confidence: 99%

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation

et al. 2016

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Dengue virus (DENV) infection causes organ injuries, and the liver is one of the most important sites of DENV infection, where viral replication generates a high viral load. The molecular mechanism of DENV-induced liver injury is still under investigation. The mitogen activated protein kinases (MAPKs), including p38 MAPK, have roles in the hepatic cell apoptosis induced by DENV. However, the in vivo role of p38 MAPK in DENV-induced liver injury is not fully understood. In this study, we investigated the role of SB203580, a p38 MAPK inhibitor, in a mouse model of DENV infection. Both the hematological parameters, leucopenia and thrombocytopenia, were improved by SB203580 treatment and liver transaminases and histopathology were also improved. We used a real-time PCR microarray to profile the expression of apoptosis-related genes. Tumor necrosis factor α, caspase 9, caspase 8, and caspase 3 proteins were significantly lower in the SB203580-treated DENV-infected mice than that in the infected control mice. Increased expressions of cytokines including TNF-α, IL-6 and IL-10, and chemokines including RANTES and IP-10 in DENV infection were reduced by SB203580 treatment. DENV infection induced the phosphorylation of p38MAPK, and its downstream signals including MAPKAPK2, HSP27 and ATF-2. SB203580 treatment did not decrease the phosphorylation of p38 MAPK, but it significantly reduced the phosphorylation of MAPKAPK2, HSP27, and ATF2. Therefore, SB203580 modulates the downstream signals to p38 MAPK and reduces DENV-induced liver injury.

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“…Especially, DENV serotypes 1, 3, and 4 have a similar entry pathway as DENV-2 (18). As reported, combined effects of ribavirin and compound A can inhibit DENV production infected with all DENV serotypes 1-4 (32). So, we proposed that rEv37 may have a similar antiviral effect on DENV-1, 3, and 4 serotypes, but it still needs to be further confirmed in future work.…”

Section: Discussionmentioning

confidence: 66%

A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles

Lang

et al. 2019

Journal of Biological Chemistry

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Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent. Here, we expressed and purified a venom peptide, Ev37, from the scorpion Euscorpiops validus in a prokaryotic system. We found that rEv37 can inhibit dengue virus type 2 (DENV-2), hepatitis C virus (HCV), Zika virus (ZIKV), and herpes simplex virus type 1 (HSV-1) infections in a dose-dependent manner at noncytotoxic concentrations, but that it has no effect on Sendai virus (SeV) and adenovirus (AdV) infections in vitro. Furthermore, rEv37 alkalized acidic organelles to prevent low pH-dependent fusion of the viral membrane-endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry. Taken together, our results indicate that the scorpion venom peptide Ev37 is a broad-spectrum antiviral agent with a specific molecular mechanism against viruses undergoing low pH-dependent fusion activation during entry into host cells. We conclude that Ev37 is a potential candidate for development as an antiviral drug.

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Inhibition of dengue virus production and cytokine/chemokine expression by ribavirin and compound A

Cited by 30 publications

References 48 publications

Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice

Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation

A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles

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