دورية أكاديمية
Molecular Docking, ADMET Analysis and Molecular Dynamics (MD) Simulation to Identify Synthetic Isoquinolines as Potential Inhibitors of SARS-CoV-2 M PRO .
| العنوان: | Molecular Docking, ADMET Analysis and Molecular Dynamics (MD) Simulation to Identify Synthetic Isoquinolines as Potential Inhibitors of SARS-CoV-2 M PRO . |
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| المؤلفون: | Dos Santos Correia PR; Institute of Chemistry and Biotechnology, Federal University of Alagoas, A. C. Simões - Tabuleiro dos Martins, 57072-970, Maceió, Alagoas, Brazil., de Souza AHD; Institute of Chemistry and Biotechnology, Federal University of Alagoas, A. C. Simões - Tabuleiro dos Martins, 57072-970, Maceió, Alagoas, Brazil., Chaparro AR; Centro de Física Aplicada y Tecnología Avanzada (CFATA), Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Boulevard Juriquilla No. 3001, CP 76230, Juriquilla, Querétaro, Mexico., Tenorio Barajas AY; Facultad de ciencias Físico matemáticas, Benemérita Universidad Autónoma de Puebla C.U. Puebla, Pue., México., Porto RS; Institute of Chemistry and Biotechnology, Federal University of Alagoas, A. C. Simões - Tabuleiro dos Martins, 57072-970, Maceió, Alagoas, Brazil. |
| المصدر: | Current computer-aided drug design [Curr Comput Aided Drug Des] 2023; Vol. 19 (5), pp. 391-404. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101265750 Publication Model: Print Cited Medium: Internet ISSN: 1875-6697 (Electronic) Linking ISSN: 15734099 NLM ISO Abbreviation: Curr Comput Aided Drug Des Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Sharjah, U.A.E. ; San Francisco, CA : Bentham Science Publishers, c2005- |
| مواضيع طبية MeSH: | SARS-CoV-2* , COVID-19*, Humans ; Molecular Dynamics Simulation ; Molecular Docking Simulation ; Isoquinolines/pharmacology ; Protease Inhibitors/pharmacology ; Antiviral Agents/pharmacology |
| مستخلص: | Background: The rapidly widespread SARS-CoV-2 infection has affected millions worldwide, thus becoming a global health emergency. Although vaccines are already available, there are still new COVID-19 cases daily worldwide, mainly due to low immunization coverage and the advent of new strains. Therefore, there is an utmost need for the discovery of lead compounds to treat COVID-19. Objective: Considering the relevance of the SARS-CoV-2 M PRO in viral replication and the role of the isoquinoline moiety as a core part of several biologically relevant compounds, this study aimed to identify isoquinoline-based molecules as new drug-like compounds, aiming to develop an effective coronavirus inhibitor. Methods: 274 isoquinoline derivatives were submitted to molecular docking interactions with SARS-CoV-2 M PRO (PDB ID: 7L0D) and drug-likeness analysis. The five best-docked isoquinoline derivatives that did not violate any of Lipinski's or Veber's parameters were submitted to ADMET analysis and molecular dynamics (MD) simulations. Results: The selected compounds exhibited docking scores similar to or better than chloroquine and other isoquinolines previously reported. The fact that the compounds interact with residues that are pivotal for the enzyme's catalytic activity, and show the potential to be orally administered makes them promising drugs for treating COVID-19. Conclusion: Ultimately, MD simulation was performed to verify ligand-protein complex stability during the simulation period. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| فهرسة مساهمة: | Keywords: ADMET; COVID-19; Isoquinoline derivatives; SARS-CoV-2; molecular docking; molecular dynamics |
| المشرفين على المادة: | 0 (Isoquinolines) 0 (Protease Inhibitors) 0 (Antiviral Agents) |
| تواريخ الأحداث: | Date Created: 20230125 Date Completed: 20230517 Latest Revision: 20230517 |
| رمز التحديث: | 20230517 |
| DOI: | 10.2174/1573409919666230123150013 |
| PMID: | 36694326 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1875-6697 |
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| DOI: | 10.2174/1573409919666230123150013 |