Characterization of the activity of 2′-C-methylcytidine against dengue virus replication

Lee, Jin‐Ching; Tseng, Chih‐Hua; Wu, Yu‐Hsuan; Kaushik‐Basu, Neerja; Lin, Ching-Cheng; Chen, Wei‐Chun; Wu, Huey-Nan

doi:10.1016/j.antiviral.2015.01.002

Cited by 65 publications

(54 citation statements)

References 27 publications

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“…The ICR suckling mouse model was adopted by several groups to evaluate antivirals and vaccine efficacy by clinical severity and survival scoring, as well as viral load reduction in brain tissue (Lee et al, 2015;Zhao et al, 2014). However, altered tropism of DENV to predominantly infect the brain due to blood-brain barrier and the uncommon route of pathogen/antivirals administration raise the question of biological and physiological relevance to humans, and therefore the appropriateness of suckling mice to model DENV infection is to be cautiously interpreted.…”

Section: Suckling Micementioning

confidence: 99%

Animal models for studying dengue pathogenesis and therapy

et al. 2015

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Section: Suckling Micementioning

confidence: 99%

Animal models for studying dengue pathogenesis and therapy

et al. 2015

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“…Antigenic diversity of DENV because of the absence of long-term cross-immunity among its 4 serotypes (DENV 1–4) allows it to induce multiple sequential infections45. DENV has an 11-kb genome that encodes a single polyprotein that is cleaved by both host and viral NS2B/NS3 protease into at least 10 mature proteins: 3 structural proteins (C, prM, and E) and 7 nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5)6. In addition, the DENV NS2B/NS3 protease inhibits the host type I interferon (IFN) pathway by cleaving a human mediator of IRF3 activation (MITA) to promote the progression of DENV infection7.…”

mentioning

confidence: 99%

Human heme oxygenase 1 is a potential host cell factor against dengue virus replication

Tseng

Lin

et al. 2016

Sci Rep

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119

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Dengue virus (DENV) infection and replication induces oxidative stress, which further contributes to the progression and pathogenesis of the DENV infection. Modulation of host antioxidant molecules may be a useful strategy for interfering with DENV replication. In this study, we showed that induction or exogenous overexpression of heme oxygenase-1 (HO-1), an antioxidant enzyme, effectively inhibited DENV replication in DENV-infected Huh-7 cells. This antiviral effect of HO-1 was attenuated by its inhibitor tin protoporphyrin (SnPP), suggesting that HO-1 was an important cellular factor against DENV replication. Biliverdin but not carbon monoxide and ferrous ions, which are products of the HO-1 on heme, mediated the HO-1-induced anti-DENV effect by non-competitively inhibiting DENV protease, with an inhibition constant (Ki) of 8.55 ± 0.38 μM. Moreover, HO-1 induction or its exogenous overexpression, rescued DENV-suppressed antiviral interferon response. Moreover, we showed that HO-1 induction by cobalt protoporphyrin (CoPP) and andrographolide, a natural product, as evidenced by a significant delay in the onset of disease and mortality, and virus load in the infected mice’s brains. These findings clearly revealed that a drug or therapy that induced the HO-1 signal pathway was a promising strategy for treating DENV infection.

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“…Nucleoside analogues have been widely used as inhibitors of numerous medically important viruses, including HIV, herpesvirus, and hepatitis B virus (10,11). Regarding flaviviruses, nucleoside analogues have been demonstrated to be efficacious in HCV replicon assays (12)(13)(14)(15)(16) and also against DENV (17)(18)(19)(20)(21), WNV (22), and YFV (23). Some of them were described as broad-spectrum inhibitors of various RNA viruses (24)(25)(26)(27).…”

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confidence: 99%

Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

Eyer

Valdés

Gil

et al. 2015

Antimicrob Agents Chemother

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The anti-TBEV effect of 2=-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2=-CMA showed no detectable cellular toxicity (CC 50 > 50 M), and the antiviral effect in culture was stable for >6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2=-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2=-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection.

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Characterization of the activity of 2′-C-methylcytidine against dengue virus replication

Cited by 65 publications

References 27 publications

Animal models for studying dengue pathogenesis and therapy

Animal models for studying dengue pathogenesis and therapy

Human heme oxygenase 1 is a potential host cell factor against dengue virus replication

Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

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