دورية أكاديمية
25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 M pro and RdRp-: an insight from molecular docking and dynamics simulation approaches.
| العنوان: | 25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 M pro and RdRp-: an insight from molecular docking and dynamics simulation approaches. |
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| المؤلفون: | Alzahrani FA; Department of Biochemistry, Faculty of Science, Embryonic Stem Cells Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Centre of Artificial Intelligence in Precision Medicines (CAIPM), King Abdulaziz University, Jeddah, Saudi Arabia., Alkarim SA; Department of Biochemistry, Faculty of Science, Embryonic Stem Cells Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Hawsawi YM; Research Center, King Faisal Specialist Hospital and Research Center, Jeddah, Kingdom of Saudi Arabia., Abdulaal WH; Centre of Artificial Intelligence in Precision Medicines (CAIPM), King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Albiheyri R; Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Kurdi B; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Alguridi H; Molecular Biology Department, Jeddah Regional Laboratory, Ministry of Health, Jeddah, Saudi Arabia., El-Magd MA; Anatomy Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Shaikh, Egypt. |
| المصدر: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023 Jul; Vol. 41 (10), pp. 4744-4755. Date of Electronic Publication: 2022 May 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: June 2012- : Oxon, UK : Taylor & Francis Original Publication: Guilderland, NY : Adenine Press, [c1983- |
| مواضيع طبية MeSH: | SARS-CoV-2* , COVID-19*, Humans ; Hydroxycholesterols/pharmacology ; Molecular Docking Simulation ; Enzyme Inhibitors ; Antiviral Agents/pharmacology ; Molecular Dynamics Simulation ; Protease Inhibitors |
| مستخلص: | The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (M pro ) of the virus mediate viral transcription and replication. Mechanistically inhibition of these proteins can hinder the transcription as well as replication of the virus. Recently oxysterols and its derivative, such as 25 (S)-hydroxycholesterol (25-HC) has shown antiviral activity against SARS-CoV-2. But the exact mechanisms and their impact on RdRp and M pro have not been explored yet. Therefore, the study aimed to identify the inhibitory activity of 25-HC against the viral enzymes RdRp and M pro simultaneously. Initially, a molecular docking simulation was carried out to evaluate the binding activity of the compound against the two proteins. The pharmacokinetics (PK) and toxicity parameters were analyzed to observe the 'drug-likeness' properties of the compound. Additionally, molecular dynamics (MD) simulation was performed to confirm the binding stability of the compound to the targeted protein. Furthermore, molecular mechanics generalized Born surface area (MM-GBSA) was used to predict the binding free energies of the compound to the targeted protein. Molecular docking simulation identified low glide energy -51.0 kcal/mol and -35.0 kcal/mol score against the RdRp and M pro, respectively, where MD simulation found good binding stability of the compound to the targeted proteins. In addition, the MM/GBSA approach identified a good value of binding free energies (ΔG bind) of the compound to the targeted proteins. Therefore, the study concludes that the compound 25-HC could be developed as a treatment and/or prevention option for SARS-CoV-2 disease-related complications. Although, experimental validation is suggested for further evaluation of the work.Communicated by Ramaswamy H. Sarma. |
| فهرسة مساهمة: | Keywords: 25-hydroxycholesterol; MD simulation; RdRp; SARS-CoV-2; main protease; molecular docking; spike glycoprotein |
| المشرفين على المادة: | 0 (Hydroxycholesterols) 0 (Enzyme Inhibitors) 0 (Antiviral Agents) 0 (Protease Inhibitors) |
| تواريخ الأحداث: | Date Created: 20220505 Date Completed: 20230612 Latest Revision: 20230612 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1080/07391102.2022.2072392 |
| PMID: | 35510619 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1538-0254 |
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| DOI: | 10.1080/07391102.2022.2072392 |