ADME analysis, metabolic prediction, and molecular docking of lipoic acid with SARS-CoV-2 Omicron spike protein

Abstract

Abstract Lipoic acid (ALA), also known as 1,2-dithiolane-3-pentanoic acid, is a natural antioxidant and a critical component of mitochondrial function, where it participates in several key enzymatic processes. This organosulfur compound is derived from both plant and animal sources and was initially studied as a potential substitute for acetate. This study aims to examine the parameters related to ADME, metabolic, and structural binding analyses. Furthermore, a molecular docking analysis was performed to explore how ALA interacts with the Omicron variant of SARS-CoV-2. The study revealed that ALA exhibited high gastrointestinal absorption (GI absorption) and a Log Kp (skin permeation) value of -6.37 cm/s. The compound showed compliance with drug-likeness rules, including Lipinski, Ghose, Veber, Egan, and Muegge criteria, but was flagged with a Brenk alert due to the disulfide bond. It demonstrated acute oral toxicity and eye irritation/corrosion, with chemical reactivity involving epoxidation of the oxygen double bond, quinonation, and N-dealkylation processes. In contrast, there was a strong conjugation reaction with UDP-glucuronosyltransferase (UGT) and moderate reactivity with glutathione (GSH), sulfur, and adjacent carbons. Protein interactions displayed medium reactivity, while DNA reactivity was moderate. Additionally, the compound showed limited reactions in unstable oxidation processes and other pathways but exhibited affinity for various enzymes and receptors, including cyclooxygenase-2 and acetylcholinesterase. Molecular docking revealed a predominance of conventional hydrogen bonding with an affinity of -4.4 kcal/mol. These findings suggest a promising pharmacological profile, warranting further investigation into its clinical effects and applications.

Keywords

• In Sílico
• Docking molecular
• COVID-19
• UDP-glucuronosyltransferase
• Glutathione
• Quinonation