Drugs and Drug Candidates

Background/Objectives: Natural products, especially plant metabolites, play a crucial role in drug development and are widely used in medicine, cosmetics, and nutrition. The present review aims to provide a comprehensive overview of the pharmacological profile of Glycyrrhizin (GL), with a specific focus on its molecular targets. Methods: Scientific literature was thoroughly retrieved from reputable databases, including Scopus, Web of Science, and PubMed, up to 30 July 2025. The keywords “glycyrrhizin” and “glycyrrhizic acid” were used to identify relevant references, with a focus on pharmacological applications. Studies on synthetic analogs, non-English publications, non-pharmacological applications, and GL containing crude extracts were largely excluded. Results: Glycyrrhizin, the major bioactive constituent of Glycyrrhiza glabra, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, hepatoprotective, antitumor, neuroprotective, and immunomodulatory effects. These actions are primarily mediated through the inhibition of high-mobility group box 1 (HMGB1) and the modulation of key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and various cytokine networks. As a result of its therapeutic potential, GL-based formulations, including Stronger Neo-Minophagen C, and GL-rich extracts of G. glabra are commercially available as pharmaceutical preparations and food additives. Conclusions: Despite its therapeutic potential, the clinical application of GL is limited by poor oral bioavailability, metabolic variability, and adverse effects such as pseudoaldosteronism. Hence, careful consideration of pharmacokinetics and safety is essential for translating its therapeutic potential into clinical practice.

In the published publication [...]

Background/Objectives: Human Herpes Simplex Virus 1 (HSV-1) is a common pathogen that establishes lifelong latent infections. The emergence of drug resistance necessitates novel therapeutic strategies. This study introduces a novel antiviral approach: a bivalent degrader designed to induce the degradation of an essential protein. Methods: A structural model of ICP0, generated via the Chai-1 AI platform, was analyzed with fpocket, P2Rank, and KVFinder to identify a superior allosteric target site. An iterative de novo design workflow with CReM-dock then yielded a lead scaffold based on its predicted affinity and drug-like properties. This selected “warhead” was used to rationally design the final bivalent degrader, ICP0-deg-01, for the ICP0 dimer model. Results: The generative process yielded a lead chemical scaffold that was selected based on its predicted binding affinity and favorable drug-like properties. This scaffold was used to rationally design a single candidate bivalent degrader, ICP0-deg-01. Our structural model predicts that ICP0-deg-01 can successfully bridge two ICP0 protomers, forming an energetically favorable ternary complex. Conclusions: This work provides a computational proof-of-concept for a novel class of anti-herpetic agents and identifies a lead candidate for future molecular dynamics simulations and experimental validation.