A pan-serotype antiviral to prevent and treat dengue: A journey from discovery to clinical development driven by public-private partnerships

Goethals, Olivia; Voge, Natalia Victoria; Kesteleyn, Bart; Chaltin, Patrick; Jinks, Tim; Marez, Tine De; Koul, Anil; Draghia-Akli, Ruxandra; Neyts, Johan; Loock, Marnix Van

doi:10.1016/j.antiviral.2022.105495

Cited by 9 publications

(3 citation statements)

References 22 publications

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“…In mouse and non-human primate models, this drug can inhibit DENV [211]. A phase 1 clinical trial of JNJ-1802 was successfully completed in humans, and it was safe and well tolerated in healthy individuals [212] (NCT05201794) as well as for patients with confirmed DENV (NCT04906980) [162].…”

Section: Ns4a and Ns4b Targetingmentioning

confidence: 99%

Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview

Diani,

Lagni,

Lotti

et al. 2023

Microorganisms

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Flaviviruses cause numerous pathologies in humans across a broad clinical spectrum with potentially severe clinical manifestations, including hemorrhagic and neurological disorders. Among human flaviviruses, some viral proteins show high conservation and are good candidates as targets for drug design. From an epidemiological point of view, flaviviruses cause more than 400 million cases of infection worldwide each year. In particular, the Yellow Fever, dengue, West Nile, and Zika viruses have high morbidity and mortality—about an estimated 20,000 deaths per year. As they depend on human vectors, they have expanded their geographical range in recent years due to altered climatic and social conditions. Despite these epidemiological and clinical premises, there are limited antiviral treatments for these infections. In this review, we describe the major compounds that are currently under evaluation for the treatment of flavivirus infections and the challenges faced during clinical trials, outlining their mechanisms of action in order to present an overview of ongoing studies. According to our review, the absence of approved antivirals for flaviviruses led to in vitro and in vivo experiments aimed at identifying compounds that can interfere with one or more viral cycle steps. Still, the currently unavailability of approved antivirals poses a significant public health issue.

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Section: Ns4a and Ns4b Targetingmentioning

confidence: 99%

Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview

Diani,

Lagni,

Lotti

et al. 2023

Microorganisms

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“…Currently, concerns are that the vaccine may not protect vaccinees against all serotypes of DENV and that the immune response may decline over time. , Thus, no large-scale prophylaxis or treatment is currently available, underscoring the need to develop a potent antiviral small molecule which has balanced efficacy against all four serotypes of DENV. We envision that to prevent and treat dengue fever, an integrated approach is needed, combining vaccines, small-molecule antivirals, vector control, diagnostics, and education/communication …”

Section: Introductionmentioning

confidence: 99%

“…We envision that to prevent and treat dengue fever, an integrated approach is needed, combining vaccines, small-molecule antivirals, vector control, diagnostics, and education/communication. 26 We previously described the identification and structure− activity relationship (SAR) of a series of 3-acyl-indole derivatives that act as potent and pan-serotype inhibitors of DENV. 27,28 These inhibitors have been shown to block viral replication by preventing the interaction between the DENV nonstructural proteins NS3 and NS4B.…”

Section: ■ Introductionmentioning

confidence: 99%

Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor

Kesteleyn,

Bonfanti,

Bardiot

et al. 2024

J. Med. Chem.

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Dengue is a global public health threat, with about half of the world's population at risk of contracting this mosquito-borne viral disease. Climate change, urbanization, and global travel accelerate the spread of dengue virus (DENV) to new areas, including southern parts of Europe and the US. Currently, no denguespecific small-molecule antiviral for prophylaxis or treatment is available. Here, we report the discovery of JNJ-1802 as a potent, pan-serotype DENV inhibitor (EC 50 's ranging from 0.057 to 11 nM against the four DENV serotypes). The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in human hepatocytes, the absence of major in vitro pharmacology safety alerts, and a doseproportional increase in efficacy against DENV-2 infection in mice were all supportive of its selection as a development candidate against dengue. JNJ-1802 is being progressed in clinical studies for the prevention or treatment of dengue.

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A scientific career from the early 1960s till 2023: A tale of the various protagonists

De Clercq

2024

Biochemical Pharmacology

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A pan-serotype antiviral to prevent and treat dengue: A journey from discovery to clinical development driven by public-private partnerships

Cited by 9 publications

References 22 publications

Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview

Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview

Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor

A scientific career from the early 1960s till 2023: A tale of the various protagonists

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