Computational medicinal chemistry role in clinical pharmacy education: Ingavirin for coronavirus disease 2019 (COVID-19) discovery model

ABSTRACT

Objective: Given the major shift to patient-directed education, novel coronavirus (nCoV) provides a live example on how medicinal chemistry could be a key science to teach pharmacy students. In this paper, students and clinical pharmacy practitioners will find a stepwise primer on identifying new potential nCoV treatments mechanistically modulated through angiotensin-converting enzyme 2 (ACE2). Methods: First, we identified the maximum common pharmacophore between carnosine and melatonin as background ACE2 inhibitors. Second, we performed a similarity search to spot out structures containing the pharmacophore. Third, molinspiration bioactivity scoring enabled us to promote one of the newly identified molecules as the best next candidate for nCoV. Preliminary docking in SwissDock and visualization through University of California San Francisco (UCSF) chimera made it possible to qualify one of them for further detailed docking and experimental validation. Results: Ingavirin had the best docking results with full fitness of −3347.15 kcal/mol and estimated ΔG of −8.53 kcal/mol compared with melatonin (−6.57 kcal/mol) and carnosine (−6.29 kcal/mol). UCSF chimera showed viral spike protein elements binding to ACE2 retained in the best ingavirin pose in SwissDock at 1.75 Angstroms. Conclusion: Ingavirin has a promising inhibitory potential to host (ACE2 and nCoV spike protein) recognition, and hence could offer the next best mitigating effect against the current coronavirus disease (COVID-19) pandemic. (AU)