RESUMO
This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.
Assuntos
Tratamento Farmacológico da COVID-19 , Proteases 3C de Coronavírus , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , SARS-CoV-2 , SARS-CoV-2/efeitos dos fármacos , Humanos , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Antivirais/química , Antivirais/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Ligação de Hidrogênio , Ligantes , COVID-19/virologia , Ligação ProteicaRESUMO
A hypothetical study by using molecular modeling for antioxidant capacity of kojic acid derivatives was performed using quantum chemistry calculations by DFT/B3LYP/6-311++G(3d,2p). Four modification approaches were considered namely simplification, functional modifications, ring regioisomerism, and hydroxylation. Molecular orbitals, single-electron transfers, hydrogen atom transfers, and spin density distributions were used for antioxidant prediction. In accordance with HOMO, LUMO, Gap, ionization potential, bond dissociation energy, and stabilization energy, the molecular simplifications of kojic acid show that enol moiety is more important for antioxidant capacity than alcohol group. Few molecular modifications on alcohol or enol position were more potent than kojic acid. The π conjugation system among ether, alkene, and hydroxyl moieties can be involved on resonance effects of better compounds. A different performance was observed on alcohol molecular modifications when compared to enol position. All lactone derivatives were more potent than kojic acid on both mechanisms, and their hydroxylated derivatives were more potent than ascorbic acid. In conclusion, the ring regioisomers and its hydroxylated derivatives have better antioxidant capacity than kojic acid. Graphical Abstract The theoretical study using molecular modeling for antioxidant capacity prediction of kojic acid was more related to enol moiety than alcohol. The regioisomerism and hybrid derivatives show that the lactone derivatives increase antioxidant capacity more than the pyrone derivatives.