Abstract:
The coronavirus, a subfamily of the Coronavirinae family, is an RNA virus with over 40 variations that can infect humans, non-human mammals, and birds. Among the seven types of human corona viruses, SARS-CoV-2 is responsible for the current COVID-19 pandemic. The focus of the current study is to identify drug molecules for the treatment of COVID-19 by targeting human proteases, specifically transmembrane serine protease 2 (TMPRSS2), furin, cathepsin B, and a nuclear receptor named farnesoid X receptor (FXR). TMPRSS2 and furin play a role in cleaving the spike protein of the SARS-CoV-2 virus, while cathepsin B is critical for the virus's entry and pathogenesis. FXR, on the other hand, regulates the expression of ACE2, and inhibiting it can reduce SARS-CoV-2 infection. By inhibiting these four protein targets with non-toxic inhibitors, the entry of the infectious agent into host cells and its pathogenesis can be obstructed. In the study, the BioSolveIT suite was used for pharmacophore-based computational drug design. A total of 1611 ligands from the ligand library were docked with the target proteins to identify potent inhibitors based on the pharmacophore. After conducting ADME analysis and assessing protein-ligand interactions, potent druggable inhibitors of the target proteins were obtained. Compounds 26, 29, and 30 were identified as potent inhibitors of TMPRSS2, while compounds 6, 12, 13, 14, 25, and 31 showed inhibition of FXR. For cathepsin B, compounds 2 and 7 were identified as the most druggable inhibitors. Lastly, compounds 5 and 20 exhibited activity against furin.
Page(s):
388-388
DOI:
DOI not available
Published:
Journal: Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23, Volume: 0, Issue: 0, Year: 2023