Synthesis, characterization, and in silico analysis against SARS CoV-2 of novel benzimidazolium salts

In acute conditions, vaccines are very important, although they provide antibodies for fighting against COVID19 for a certain period. It is necessary to produce an anti-viral agent for a usual healing process against SARS CoV-2 which is responsible the pandemic we are living in. Many drugs with benzimidazole main scaffold are still used in a wide variety of treatment procedures. In this case, substituted benzimidazole structures could be good candidates for fighting against COVID-19. Theoretical calculation methods could be a key tool for overcome the difficulties of individual analyzing of each new structure. In this study, new benzimidazole structures were synthesized and characterized for in silico evaluation as anti-viral agent. The molecules were optimized and analyzed for reactivity with Koopmans Theorem. Also, molecular docking simulations were performed for SARS coronavirus main peptidase (PDB ID: 2GTB), COVID-19 main protease (PDB ID: 5R82), and papain-like protease of SARS CoV-2 (PDB ID: 6W9C) crystals.

Molecular docking, molecular dynamics simulations and reactivity, studies on approved drugs library targeting ACE2 and SARS-CoV-2 binding with ACE2.

The recent new contagion coronavirus 2019 (COVID-19) disease is a new generation of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 which infected millions confirmed cases and hundreds of thousands death cases around the world so far. Molecular docking combined with molecular dynamics is one of the most important tools of drug discovery and drug design, which it used to examine the type of binding between the ligand and its protein enzyme. Global reactivity has important properties, which enable chemists to understand the chemical reactivity and kinetic stability of compounds. In this study, molecular docking and reactivity were applied for eighteen drugs, which are similar in structure to chloroquine and hydroxychloroquine, the potential inhibitors to angiotensin-converting enzyme (ACE2). Those drugs were selected from DrugBank. The reactivity, molecular docking and molecular dynamics were performed for two receptors ACE2 and [SARS-CoV-2/ACE2] complex receptor in two active sites to find a ligand, which may inhibit COVID-19. The results obtained from this study showed that Ramipril, Delapril and Lisinopril could bind with ACE2 receptor and [SARS-CoV-2/ACE2] complex better than chloroquine and hydroxychloroquine. This new understanding should help to improve predictions of the impact of such alternatives on COVID-19.Communicated by Ramaswamy H. Sarma.