We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was −9.9 kcal/mol and for the chloroquine of −10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.

In this work, we carried out a theoretical investigation regarding amphetamine-type stimulants, which can cause central nervous system degeneration, interacting with human DNA. These include amphetamine, methamphetamine, 3,4-Methylenedioxymethamphetamine (also known as ecstasy), as well as their main metabolites. The studies were performed through molecular docking and molecular dynamics simulations, where molecular interactions of the receptor-ligand systems, along with their physical-chemical energies, were reported. Our results show that 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine (ecstasy) present considerable reactivity with the receptor (DNA), suggesting that these molecules may cause damage due to human-DNA. These results were indicated by free Gibbs change of bind (ΔG) values referring to intermolecular interactions between the drugs and the minor grooves of DNA, which were predominant for all simulations. In addition, it was observed that 3,4-Dihydroxymethamphetamine (ΔG = -13.15 kcal/mol) presented greater spontaneity in establishing interactions with DNA in comparison to 3,4-Methylenedioxymethamphetamine (ΔG = -8.61 kcal/mol). Thus, according with the calculations performed our results suggest that the 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine have greater probability to provide damage to human DNA fragments.

This present work aims to investigate the physical chemical interactions between cocaine and its metabolites with the human-DNA. The investigation was performed by molecular docking and molecular dynamics calculations, where the following cocaine metabolites were analyzed: Benzoylecgonine, Cocaethylene, Ester methylecgonine and Norcocaine. From the docking simulations we observed the hydrogen interactions most likely to occur between the drugs and DNA, whereas, through the molecular dynamics, the RMSD values were obtained and analyzed along with van der Waals, electrostatic, solvation and bind free energies between DNA and cocaine, beside its metabolites. Our results showed that the guanine in the minor groove of DNA is the nucleotide with highest chemical affinity to interact with the cocaine metabolites. On the other hand, the cocaethylene and cocaine were the drugs which presented the most stable and strong interactions with DNA, which can suggest, from molecular modeling investigations, a possible genotoxic potential of these molecules.