Article ; Online: Highlights in TMPRSS2 inhibition mechanism with guanidine derivatives approved drugs for COVID-19 treatment.
Journal of biomolecular structure & dynamics
2023 Volume 41, Issue 22, Page(s) 12908–12922
Abstract: Transmembrane protease serine 2 (TMPRSS2) has been identified as a critical key for the entry of coronaviruses into human cells by cleaving and activating the spike protein of SARS-CoV-2. To block the TMPRSS2 function, 18 approved drugs, containing the ... ...
| Abstract | Transmembrane protease serine 2 (TMPRSS2) has been identified as a critical key for the entry of coronaviruses into human cells by cleaving and activating the spike protein of SARS-CoV-2. To block the TMPRSS2 function, 18 approved drugs, containing the guanidine group were tested against TMPRSS2's ectodomain (7MEQ). Among these drugs, Famotidine, Argatroban, Guanadrel and Guanethidine strongly binds with TMPRSS2 S1 pocket with estimated Fullfitness energies of -1847.12, -1630.87, -1605.81 and -1600.52 kcal/mol, respectively. A significant number of non-covalent interactions such as hydrogen bonding, hydrophobic and electrostatic interactions were detected in protein-ligand complexes. In addition, the ADMET analysis revealed a perfect concurrence with the aptitude of these drugs to be developed as an anti-SARS-CoV-2 therapeutics. Further, MD simulation and binding free energy calculations were performed to evaluate the dynamic behavior and stability of protein-ligand complexes. The results obtained herein highlight the enhanced stability and good binding affinities of the Argatroban and Famotidine towards the target protein, hence might act as new scaffolds for TMPRSS2 inhibition.Communicated by Ramaswamy H. Sarma. |
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| MeSH term(s) | Humans ; COVID-19 ; COVID-19 Drug Treatment ; Famotidine ; Ligands ; SARS-CoV-2 ; Antihypertensive Agents ; Guanidines/pharmacology ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protease Inhibitors/pharmacology ; Serine Endopeptidases |
| Chemical Substances | argatroban (IY90U61Z3S) ; Famotidine (5QZO15J2Z8) ; Ligands ; Antihypertensive Agents ; Guanidines ; Protease Inhibitors ; TMPRSS2 protein, human (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-) |
| Language | English |
| Publishing date | 2023-01-29 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 49157-3 |
| ISSN | 1538-0254 ; 0739-1102 |
| ISSN (online) | 1538-0254 |
| ISSN | 0739-1102 |
| DOI | 10.1080/07391102.2023.2169762 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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