Drug intelligence / Profile preview

ribavirin + pleconaril

Development stage
Phase 2
Lead developer
Oslo University Hospital
Modality
Small Molecules
Administration
Oral
01

Overview

Ribavirin + pleconaril is an oral combination of two small-molecule antiviral agents, each with distinct mechanisms of action. Ribavirin is a nucleoside analog with broad-spectrum activity against several DNA and RNA viruses, including enteroviruses. It acts by increasing the mutation frequency in viral genomes (error catastrophe), inhibiting inosine monophosphate dehydrogenase (IMPDH) to deplete GTP pools, and modulating host immune responses toward a Th1 phenotype[6]. Pleconaril targets picornaviruses by binding to a hydrophobic pocket in viral protein 1 (VP1) on the capsid, preventing uncoating of viral RNA and thus blocking infection[8]. The combination has been investigated primarily for its potential to preserve pancreatic β-cell function in new-onset type 1 diabetes (T1D), based on evidence that low-grade enterovirus infection may contribute to T1D pathogenesis[1][2][4][5]. In phase 2 clinical trials, this regimen showed moderate efficacy in slowing the decline of endogenous insulin production over one year compared to placebo; however, benefits were not sustained at three years[2][4][5]. The combination was generally well tolerated.

Other names
Apovir
02

Targets

IMPDH (Inosine-5'-monophosphate dehydrogenase 1)VP1 pocket (VP1 capsid hydrophobic pocket)vRNA (Coronavirus viral RNA)

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