In silico study of the interactions of Pilocarpus microphyllus imidazolic alkaloids with the main protease (Mpro) of SARS-CoV-2

Abstract

ABSTRACT The disease outbreak caused by SARS-CoV-2 continues to rise worldwide, even in countries which have considered it controlled. As new cases appear daily, infecting millions of people and causing thousands of deaths, the current in silico study aims to investigate the imidazolic alkaloids of the species Pilocarpus microphyllus (Jaborandi) as a potential inhibitory activity against the Mpro protease from SARS-CoV-2, since it plays a fundamental role in the processing of polyproteins that are translated from viral RNA. Jaborandi is distributed in some Brazilian biomes, being easily identified, yet little researched, with proven anti-inflammatory, contraceptive, anti-diabetic and gastroprotective activities. In this work, DFT calculation of thermodynamic properties, electrostatic potential surface, frontier molecular orbitals and descriptors of chemical reactivity of imidazolic alkaloids were associated with the use of molecular docking techniques, molecular dynamics and ADMET predictions. One can verify a good reactivity chemistry and energetic stability of epiisopiloturine, epiisopilosine, isopilosine and e pilosine with some residues of amino acids present in the active site of the main protease of COVID-19. In this sense, the results point out to the imidazolic alkaloids of Jaborandi as promising targets for in vitro and in vivo tests, as possible candidates for inhibitors of the enzyme Mpro.