Structure-based identification of potential SARS-CoV-2 main protease inhibitors
| Autor: | Mohamed F. Alajmi, Zeynab Fakhar, Imtaiyaz Hassan, Aijaz Ahmad, Deeba Shamim Jairajpuri, Shama Khan, Afzal Hussain |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
Molecular model COVID19 medicine.medical_treatment media_common.quotation_subject 030303 biophysics Computational biology Molecular Dynamics Simulation medicine.disease_cause 03 medical and health sciences Main protease inhibitor Structural Biology medicine Humans Protease Inhibitors Molecular Biology Coronavirus 3C Proteases Coronavirus media_common Pharmacophore modeling chemistry.chemical_classification 0303 health sciences Protease SARS-CoV-2 Molecular dynamics simulations General Medicine COVID-19 Drug Treatment Molecular Docking Simulation Enzyme ADMET Viral replication chemistry Docking (molecular) Molecular docking Pharmacophore Research Article |
| Zdroj: | Journal of Biomolecular Structure & Dynamics article-version (VoR) Version of Record Journal of Biomolecular Structure and Dynamics |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | To address coronavirus disease (COVID-19), currently, no effective drug or vaccine is available. In this regard, molecular modeling approaches are highly useful to discover potential inhibitors of the main protease (Mpro) enzyme of SARS-CoV-2. Since, the Mpro enzyme plays key roles in mediating viral replication and transcription; therefore, it is considered as an attractive drug target to control SARS-CoV-2 infection. By using structure-based drug design, pharmacophore modeling, and virtual high throughput drug screening combined with docking and all-atom molecular dynamics simulation approach, we have identified five potential inhibitors of SARS-CoV-2 Mpro. MD simulation studies revealed that compound 54035018 binds to the Mpro with high affinity (ΔGbind −37.40 kcal/mol), and the complex is more stable in comparison with other protein-ligand complexes. We have identified promising leads to fight COVID-19 infection as these compounds fulfill all drug-likeness properties. However, experimental and clinical validations are required for COVID-19 therapy. Communicated by Ramaswamy H. Sarma |
| Databáze: | OpenAIRE |
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