| Autor: |
Santiago-Silva, Kaio Maciel de, Camargo, Priscila, Felix da Silva Gomes, Gabriel, Sotero, Ana Paula, Orsato, Alexandre, Perez, Carla Cristina, Nakazato, Gerson, da Silva Lima, Camilo Henrique, Bispo, Marcelle |
| Zdroj: |
Journal of Biomolecular Structure and Dynamics; November 2023, Vol. 41 Issue: 16 p7686-7699, 14p |
| Abstrakt: |
AbstractThe coronavirus disease-2019 (COVID-19) pandemic, caused by the novel coronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), became the highest public health crisis nowadays. Although the use of approved vaccines for emergency immunization and the reuse of FDA-approved drugs remains at the forefront, the search for new, more selective, and potent drug candidates from synthetic compounds is also a viable alternative to combat this viral disease. In this context, the present study employed a computational virtual screening approach based on molecular docking and molecular dynamics (MD) simulation to identify possible inhibitors for SARS-CoV-2 Mpro(main protease), an important molecular target required for the maturation of the various polyproteins involved in viral replication. The virtual screening approach selected four potential inhibitors against SARS-CoV-2 Mpro. In addition, MD simulation studies revealed changes in the positions of the ligands during the simulations compared to the complex obtained in the molecular docking studies, showing the benzoylguanidines LMed-110and LMed-136have a higher affinity for the active site compared to the other structures that tended to leave the active site. Besides, there was a better understanding of the formation and stability of the existing H-bonds in the formed complexes and the energetic contributions to the stability of the target-ligand molecular complexes. Finally, the in silicoprediction of the ADME profile suggested that LMed-136has drug-like characteristics and good pharmacokinetic properties. Therefore, from the present study, it can be suggested that these structures can inhibit SARS-CoV-2 Mpro. Nevertheless, further studies are needed in vitroassays to investigate the antiviral properties of these structures against SARS-CoV-2. |
| Databáze: |
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