Delving into the Latest Updates on Pleconaril with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Picovir, Pleconaril (USAN/INN)

+ [5]

Target-

Mechanism

Virus replication inhibitors

Therapeutic Areas

Immune System DiseasesEndocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus, Type 1

Inactive Indication

AsthmaCommon ColdEnterovirus Infections+ [3]

Originator Organization

Sanofi

Active Organization

Oslo universitetssykehus HF

Inactive Organization

National Institute of Allergy & Infectious Diseases

Merck Sharp & Dohme Corp.

Sanofi

+ [3]

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

Structure

Molecular FormulaC18H18F3N3O3

InChIKeyKQOXLKOJHVFTRN-UHFFFAOYSA-N

CAS Registry153168-05-9

This is a randomized, multi-center, double-blind, placebo-controlled study evaluating the efficacy of pleconaril nasal spray in preventing asthma exacerbation and common cold symptoms in asthmatic participants exposed to picornavirus respiratory infections. Participants will be assigned treatment with pleconaril or placebo nasal spray for 7 days (14 doses). Participants will be followed for an additional 14 days.

Start Date01 Aug 2006

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Pleconaril

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100 Translational Medicine associated with Pleconaril

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100 Patents (Medical) associated with Pleconaril

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162

Literatures (Medical) associated with Pleconaril

01 Apr 2024·Antiviral Research

The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants

Article

Author: Wolthers, Katja C ; Kainov, Denis E ; Bjørås, Magnar ; Lysvand, Hilde ; Oksenych, Valentyn ; Ianevski, Aleksandr ; Smura, Teemu ; Tenson, Tanel ; Afset, Jan Egil ; Schjelderup Nilsen, Hans-Johnny ; Frøysa, Irene Trøen ; Galabov, Angel S ; Sridhar, Adithya ; Zusinaite, Eva ; Kurg, Reet ; Calitz, Carlemi ; Stoyanova, Adelina ; Høyer, Erling

Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro. We identified several novel, synergistic two-drug and three-drug combinations that demonstrated significant inhibition of enterovirus infections in vitro. Specifically, the triple-drug combination of pleconaril, rupintrivir, and remdesivir exhibited remarkable efficacy against echovirus (EV) 1, EV6, EV11, and coxsackievirus (CV) B5, in human lung epithelial A549 cells. This combination surpassed the effectiveness of single-agent or dual-drug treatments, as evidenced by its ability to protect A549 cells from EV1-induced cytotoxicity across seven passages. Additionally, this triple-drug cocktail showed potent antiviral activity against EV-A71 in human intestinal organoids. Thus, our findings highlight the therapeutic potential of the pleconaril-rupintrivir-remdesivir combination as a broad-spectrum treatment option against a range of enterovirus infections. The study also paves the way towards development of strategic antiviral drug combinations with virus family coverage and high-resistance barriers.

01 Feb 2024·Antiviral Research

Molecular mechanism of rhinovirus escape from the Pyrazolo[3,4-d]pyrimidine capsid-binding inhibitor OBR-5-340 via mutations distant from the binding pocket: Derivatives that brake resistance

Article

Author: Makarov, Vadim ; Richter, Martina ; Döring, Kristin ; Schmidtke, Michaela ; Kazakova, Elena ; Egorova, Anna ; Blaas, Dieter ; Khrenova, Maria ; Riabova, Olga

Rhinoviruses (RVs) cause the common cold. Attempts at discovering small molecule inhibitors have mainly concentrated on compounds supplanting the medium chain fatty acids residing in the sixty icosahedral symmetry-related hydrophobic pockets of the viral capsid of the Rhinovirus-A and -B species. High-affinity binding to these pockets stabilizes the capsid against structural changes necessary for the release of the ss(+) RNA genome into the cytosol of the host cell. However, single-point mutations may abolish this binding. RV-B5 is one of several RVs that are naturally resistant against the well-established antiviral agent pleconaril. However, RV-B5 is strongly inhibited by the pyrazolopyrimidine OBR-5-340. Here, we report on isolation and characterization of RV-B5 mutants escaping OBR-5-340 inhibition and show that substitution of amino acid residues not only within the binding pocket but also remote from the binding pocket hamper inhibition. Molecular dynamics network analysis revealed that strong inhibition occurs when an ensemble of several sequence stretches of the capsid proteins enveloping OBR-5-340 move together with OBR-5-340. Mutations abrogating this dynamic, regardless of whether being localized within the binding pocket or distant from it result in escape from inhibition. Pyrazolo [3,4-d]pyrimidine derivatives overcoming OBR-5-340 escape of various RV-B5 mutants were identified. Our work contributes to the understanding of the properties of capsid-binding inhibitors necessary for potent and broad-spectrum inhibition of RVs.

01 Nov 2023·Nature MedicineQ1 · MEDICINE

Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial

Q1 · MEDICINE

Article

Author: Ludvigsson, Johnny ; Roald, Trine ; Hanssen, Kristian F ; Hessel, Trine Witzner ; Mørk, Freja Barrett ; Hyöty, Heikki ; Ponzi, Erica ; Johannesen, Jesper ; Westman, Jacob ; Krogvold, Lars ; Lindblom, Nina ; Barker, Peter ; Mynarek, Ida Maria ; Dahl-Jørgensen, Knut

AbstractPrevious studies showed a low-grade enterovirus infection in the pancreatic islets of patients with newly diagnosed type 1 diabetes (T1D). In the Diabetes Virus Detection (DiViD) Intervention, a phase 2, placebo-controlled, randomized, parallel group, double-blind trial, 96 children and adolescents (aged 6–15 years) with new-onset T1D received antiviral treatment with pleconaril and ribavirin (n = 47) or placebo (n = 49) for 6 months, with the aim of preserving β cell function. The primary endpoint was the mean stimulated C-peptide area under the curve (AUC) 12 months after the initiation of treatment (less than 3 weeks after diagnosis) using a mixed linear model. The model used longitudinal log-transformed serum C-peptide AUCs at baseline, at 3 months, 6 months and 1 year. The primary endpoint was met with the serum C-peptide AUC being higher in the pleconaril and ribavirin treatment group compared to the placebo group at 12 months (average marginal effect = 0.057 in the linear mixed model; 95% confidence interval = 0.004–0.11, P = 0.037). The treatment was well tolerated. The results show that antiviral treatment may preserve residual insulin production in children and adolescent with new-onset T1D. This provides a rationale for further evaluating antiviral strategies in the prevention and treatment of T1D. European Union Drug Regulating Authorities Clinical Trials identifier: 2015-003350-41.

100 Deals associated with Pleconaril

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External Link

KEGG	Wiki	ATC	Drug Bank
D05528	Pleconaril	J05AX06	DB05105

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Systemic Inflammatory Response Syndrome	NDA/BLA	CA	National Institute of Allergy & Infectious Diseases	27 Jun 2001
Enterovirus Infections	Phase 3	CA	National Institute of Allergy & Infectious Diseases	27 Jun 2001
Systemic Inflammatory Response Syndrome	Phase 3	US	National Institute of Allergy & Infectious Diseases	27 Jun 2001
Picornaviridae Infections	Phase 1	-	Antivirus Therapeutics, Inc.	-
Picornaviridae Infections	Phase 1	-	Sanofi	-
Enterovirus Infections	Preclinical	US	National Institute of Allergy & Infectious Diseases	27 Jun 2001
Picornaviridae Infections	Preclinical	-	Merck Sharp & Dohme Corp.	-
Picornaviridae Infections	Preclinical	-	Shire Pharmaceuticals Services Ltd.	-
Picornaviridae Infections	Preclinical	-	ViroPharma Incorporated	-
Common Cold	Discovery	-	Merck Sharp & Dohme Corp.	01 Aug 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00394914 (CTgov)	Phase 2	Rhinovirus infection \| Common Cold \| Asthma	311	Pleconaril (Pleconaril)	ummbyjhiyl(yhhaxvwydg) = phudsxphji rnhgoqvtzh (qxacfdyfmf, oamjdhczar - woumljnurn) View more	-	31 Oct 2013
				Placebo to Pleconaril (Placebo)	ummbyjhiyl(yhhaxvwydg) = nsgmvcreiu rnhgoqvtzh (qxacfdyfmf, ssppvcugxi - siwhofcrui) View more