Review of Current Dengue Treatment and Therapeutics in Development

Dn, Fusco; Chung, Richard

doi:10.4172/1948-593x.s8-002

Cited by 5 publications

(3 citation statements)

References 161 publications

(206 reference statements)

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“…Among the identified compounds, only a few have been further evaluated in preclinical or clinical trials ( Troost and Smit, 2020 ). The difficulty that has arisen in finding effective treatments is related to the toxicity of some compounds evaluated, as has been reported in other investigations ( Lim et al, 2013b ; Tay et al, 2013 ; Caillet-Saguy et al, 2014 ; Fusco and Chung, 2014 ; Lim et al, 2015 ; García et al, 2017 ), which is why it is important to continue searching for drugs. Computational tools have a large impact in drug discovery because of its fast and promising results ( Halim et al, 2017 ).…”

Section: Discussionmentioning

confidence: 98%

“…For instance, sinefungin (a SAM analog with a broad antiviral spectrum) has shown affinity six times greater than SAM for its binding site in the MTase domain ( Lim et al, 2015 ). Ribavirin, a synthetic analog of guanosine, has been shown to inhibit dengue and hepatitis C virus replication ( Chang et al, 2011 ; Tomlinson and Watowich, 2011 ); however, the use of ribavirin is limited by its oral toxicity, and its aerosol presentation diminishes its efficacy for clinical uses ( Fusco and Chung, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

“…Ivermectin is reported as an inhibitor of the α/β importin and therefore of the NS5 polymerase since it is required for its activity. There are reports that a previous treatment with ivermectin inhibits dengue virus infection in Vero cells; in addition, a pretreatment with this compound strongly inhibits the nuclear localization of NS5 during infection with DENV1 and DENV2 in BHK-21 or Huh-7 cells ( Fusco and Chung, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein

et al. 2022

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Dengue virus (DENV) is the causative agent of dengue fever. Annually, there are about 400 million new cases of dengue worldwide, and so far there is no specific treatment against this disease. The NS5 protein is the largest and most conserved viral protein among flaviviruses and is considered a therapeutic target of great interest. This study aims to search drug-like compounds for possible inhibitors of the NS5 protein in the four serotypes of DENV. Using a virtual screening from a ∼642,759-compound database, we suggest 18 compounds with NS5 binding and highlight the best compound per region, in the methyltransferase and RNA-dependent RNA polymerase domains. These compounds interact mainly with the amino acids of the catalytic sites and/or are involved in processes of protein activity. The identified compounds presented physicochemical and pharmacological properties of interest for their use as possible drugs; furthermore, we found that some of these compounds do not affect cell viability in Huh-7; therefore, we suggest evaluating these compounds in vitro as candidates in future research.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein

et al. 2022

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Diaryl Ether: A Privileged Scaffold for Drug and Agrochemical Discovery

Chen

Xiong

Yang

et al. 2020

J. Agric. Food Chem.

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Diaryl ether (DE) is a functional scaffold existing widely both in natural products (NPs) and synthetic organic compounds. Statistically, DE is the second most popular and enduring scaffold within the numerous medicinal chemistry and agrochemical reports. Given its unique physicochemical properties and potential biological activities, DE nucleus is recognized as a fundamental element of medicinal and agrochemical agents aimed at different biological targets. Its drug-like derivatives have been extensively synthesized with interesting biological features including anticancer, anti-inflammatory, antiviral, antibacterial, antimalarial, herbicidal, fungicidal, insecticidal, and so on. In this review, we highlight the medicinal and agrochemical versatility of the DE motif according to the published information in the past decade and comprehensively give a summary of the target recognition, structure–activity relationship (SAR), and mechanism of action of its analogues. It is expected that this profile may provide valuable guidance for the discovery of new active ingredients both in drug and pesticide research.

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Discovery of Dengue Virus Inhibitors

Abdullah

Lee

Chin

et al. 2020

CMC

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To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.

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Review of Current Dengue Treatment and Therapeutics in Development

Cited by 5 publications

References 161 publications

Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein

Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein

Diaryl Ether: A Privileged Scaffold for Drug and Agrochemical Discovery

Discovery of Dengue Virus Inhibitors

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