In Silico Studies of Licorice Chalcones on Three Key Enzymes Involved in HIV-1 Replication.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) is a major global health challenge. This virus undermines the immune system of infected individuals, thereby increasing their susceptibility to infectious diseases and cancer. Glycyrrhiza glabra (licorice) is a medicinal plant that is extensively used worldwide for its notable therapeutic properties. Licorice roots contain several compounds, particularly chalcones, which exhibit antiviral activity. OBJECTIVES: This study aimed to explore the inhibitory potential of licorice root-derived chalcones on three key enzymes involved in HIV-1 replication: integrase, protease, and reverse transcriptase, using an in silico method, and to evaluate the pharmacokinetic and toxicological properties of the selected compounds. METHODS: Licorice-derived chalcones were identified by searching various databases, and their molecular structures were retrieved from the PubChem database. The three-dimensional architectures of the targets, namely, integrase, protease, and reverse transcriptase, were obtained from the Protein Data Bank. Molecular docking was performed to examine the interactions between chalcones and the targets. Relevant online tools were used to predict the pharmacokinetic and toxicological properties of the selected compounds. RESULTS: Among the 30 chalcones evaluated, paratocarpin A demonstrated the most significant docking scores against all three enzymes. Furthermore, this compound exhibited better pharmacokinetic and toxicological characteristics than those of the other chalcones studied. CONCLUSION: Paratocarpine A could be considered a potential multi-target anti-HIV-1 candidate, meriting further investigation.