Identification of Synthetic 2-Mercaptobenzimidazole Derivatives as Inhibitors of Spike Protein of SARS-CoV-2 by Virtual Screening

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide and caused the COVID-19 pandemic. Despite countless efforts in searching for repositioned drugs to treat this disease, the results are still modest. Thus, searching for new compounds as promising drugs to treat this disease is crucial. 2-Mercaptobenzimidazole, a scaffold found in many biologically relevant compounds, has been extensively studied due to its range of biological activities. Using in silico tools, this study aimed to identify 2-mercaptobenzimidazole derivatives as potential drugs to inhibit SARS-CoV-2 infection by blocking spike protein – human angiotensin-converting (hACE2) enzyme interaction. 61 compounds were screened to evaluate their absorption, distribution, metabolism, and excretion (ADME) properties. The compounds that did not violate any Lipinski or Veber rules were subjected to molecular docking interactions to verify their ability to inhibit spike glycoprotein from binding to the hACE2 enzyme. The docking scores for these compounds were superior to the antiviral drugs Remdesivir and Umifenovir, proven to be potential drugs against COVID-19. Furthermore, 2-mercaptobenzimidazole derivatives have been shown to interfere in amino acids involved in key contact sites between SARS-CoV-2-CTD and hACE2 subdomain I. Finally, some toxicological properties were predicted, and the compounds exhibited few (or none) alerts for toxic endpoints as well as low predicted acute oral toxicity (LD50). In this way, the results presented in this work should contribute to discovering new drugs against SARS-CoV-2. © 2022 by the authors.

In silico studies of novel synthetic compounds as potential drugs to inhibit coronavirus (SARS-CoV-2): A systematic review

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), detected first in China, spread out fast to other parts of the world, and was soon recognized as a pandemic in March 2020. According to WHO, 179.686.071 confirmed cases and 3.899.172 deaths due to new coronavirus were reported worldwide on 26th June 2021. Despite countless efforts in searching for repositioned drugs to treat this disease, the results are still modest. Thus, the search for new molecular entities in the treatment of COVID-19 is an essential field in medicinal chemistry. Since the pandemic's beginning, several studies have reported the synthesis of novel organic compounds and their in silico interactions with the new coronavirus. Such computational studies are currently being applied to unveil the complexities of drug-target molecule interaction and also helping in developing new pharmacological treatments. This systematic review aims to provide an overview of studies describing the utilization of novel compounds as prospective drugs in the treatment of COVID-19. © 2021 by the authors.