The medicinal chemistry of Chikungunya virus

Silva-Júnior, Edeildo Ferreira da; Leoncini, G; Rodrigues, Érica Erlanny S.; Aquino, Thiago Mendonça de; Araújo-Júnior, João Xavier de

doi:10.1016/j.bmc.2017.06.049

Cited by 34 publications

(57 citation statements)

References 103 publications

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“…The global spread of alphaviruses is thought to arise from a combination of expanding mosquito populations [ 5 ], adaptation of alphaviruses to new mosquito vectors [ 6 , 7 , 8 , 9 ], and increased international travel. Currently, there are no licensed anti-viral therapies to treat alphavirus infections, but there are promising candidate small molecule inhibitors and antibody therapies [ 10 , 11 , 12 ]. Several vaccine candidates are in clinical trial [ 13 , 14 ], although to date, there are no licensed alphavirus vaccines.…”

Section: Introductionmentioning

confidence: 99%

The Alphavirus Exit Pathway: What We Know and What We Wish We Knew

Brown

Wan

Kielian

2018

Viruses

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Alphaviruses are enveloped positive sense RNA viruses and include serious human pathogens, such as the encephalitic alphaviruses and Chikungunya virus. Alphaviruses are transmitted to humans primarily by mosquito vectors and include species that are classified as emerging pathogens. Alphaviruses assemble highly organized, spherical particles that bud from the plasma membrane. In this review, we discuss what is known about the alphavirus exit pathway during a cellular infection. We describe the viral protein interactions that are critical for virus assembly/budding and the host factors that are involved, and we highlight the recent discovery of cell-to-cell transmission of alphavirus particles via intercellular extensions. Lastly, we discuss outstanding questions in the alphavirus exit pathway that may provide important avenues for future research.

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Section: Introductionmentioning

confidence: 99%

The Alphavirus Exit Pathway: What We Know and What We Wish We Knew

Brown

Wan

Kielian

2018

Viruses

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“…Moreover, the combination containing both drugs showed significant reduction in the viral titer in mice [23]. Further, the viral titer in CHIKV infected Vero cells were observed to be significantly reduced in the presence of pegylated interferon alpha [16,21,22]. However, this study is in early clinical trial phase and needs further investigation concerning its mechanism and effectiveness as potential therapy for CHIKV.…”

Section: Small Inhibitorsmentioning

confidence: 82%

“…Ribavarin antiviral activity has been reported against influenza, polio, and HCV (Flavivirus) viruses. Ribavirin was reported to inhibit dengue virus (DENV) by inhibition of post-translational capping mechanism of nascent viral mRNA [16,21,22]. Ribavirin was also reported to exhibit anti-CHIKV activity and its combination with doxycycline in 1:1 ratio showed excellent inhibition (95% inhibition) in Vero cells with an EC 50 value of 4.52 ± 1.42 μM.…”

Section: Small Inhibitorsmentioning

confidence: 99%

Antiviral therapeutics for chikungunya virus

Ghildiyal

Gabrani

2020

Expert Opinion on Therapeutic Patents

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Introduction: Chikungunya virus (CHIKV), a reemerging human arthropod borne virus, can causes global epidemic outbreaks and has become a serious health concern due to the unavailability of any antiviral therapy/vaccine. Extensive research has been conducted to target different proteins from CHIKV to curtail the spread of virus. Areas covered: This review provides an overview of the granted patents including the current status of antiviral strategies targeting CHIKV. Expert opinion: Under the current scenario, potential molecules and different approaches have been utilized to suppress CHIKV infection. MV-CHIKV and VRC-CHKVLP059-00-VP vaccine candidates have successfully completed phase I clinical trials and ribavirin (inhibitor) has shown significant inhibition of CHIKV replication and could be the most promising candidates. The drug resistance and toxicity can be modulated by using the inhibitors/drugs in combination. Moreover, nanoparticle formulations can improve the efficacy and bioavailability of drugs.

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“…potency varied according to the MOI, cell system, and assay readout (RNA levels or PFU titers). Similarly, other RNA polymerase inhibitors, such as favipiravir and ribavirin, inhibit CHIKV replication at different potencies based on the factors analyzed here plus the viral strain/genotype used (21,22,24,25,(39)(40)(41)(42). For example, the potency of ribavirin has been reported to be 341 M (42), 142 M (with a substantial error of Ϯ 126 M) (40), 10.95 M (22), 3.06 M (21), and 2.05 M (23).…”

Section: Figmentioning

confidence: 99%

Beyond Members of the Flaviviridae Family, Sofosbuvir Also Inhibits Chikungunya Virus Replication

Ferreira¹,

Reis

Freitas³

et al. 2019

Antimicrob Agents Chemother

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Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may progress to neurological impairment. Chikungunya fever (CF) is an ongoing public health problem in tropical and subtropical regions of the world, where control of the CHIKV vector, Aedes mosquitos, has failed. As there is no vaccine or specific treatment for CHIKV, patients receive only palliative care to alleviate pain and arthralgia. Thus, drug repurposing is necessary to identify antivirals against CHIKV. CHIKV RNA polymerase is similar to the orthologue enzyme of other positive-sense RNA viruses, such as members of the Flaviviridae family. Among the Flaviviridae, not only is hepatitis C virus RNA polymerase susceptible to sofosbuvir, a clinically approved nucleotide analogue, but so is dengue, Zika, and yellow fever virus replication. Here, we found that sofosbuvir was three times more selective in inhibiting CHIKV production in human hepatoma cells than ribavirin, a pan-antiviral drug. Although CHIKV replication in human induced pluripotent stem cell-derived astrocytes was less susceptible to sofosbuvir than were hepatoma cells, sofosbuvir nevertheless impaired virus production and cell death in a multiplicity of infection-dependent manner. Sofosbuvir also exhibited antiviral activity in vivo by preventing CHIKV-induced paw edema in adult mice at a dose of 20 mg/kg of body weight/day and prevented mortality in a neonate mouse model at 40- and 80-mg/kg/day doses. Our data demonstrate that a prototypic alphavirus, CHIKV, is also susceptible to sofosbuvir. As sofosbuvir is a clinically approved drug, our findings could pave the way to it becoming a therapeutic option against CF.

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The medicinal chemistry of Chikungunya virus

Cited by 34 publications

References 103 publications

The Alphavirus Exit Pathway: What We Know and What We Wish We Knew

The Alphavirus Exit Pathway: What We Know and What We Wish We Knew

Antiviral therapeutics for chikungunya virus

Beyond Members of the Flaviviridae Family, Sofosbuvir Also Inhibits Chikungunya Virus Replication

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