In Silico Screening, In Vitro Mpro Inhibitory, and Adjunctive Therapy Value of Minocycline for the Treatment of COVID-19.
What Is Known and Objective. Novel coronavirus disease (COVID-19) is still ravaging globally since its first discovery in 2019. With the continuous emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) mutant strains, therapeutic entities are still needed to be discovered. This s...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics pp. 1 - 13 |
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| Autores principales: | , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
10/9/2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=173452341&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 173452341 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: 10/9/2023 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 173452341 173452341 173452341 10.1155/2023/9955105 173452341 ppf: 1 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: In Silico Screening, In Vitro Mpro Inhibitory, and Adjunctive Therapy Value of Minocycline for the Treatment of COVID-19. aug: au: Han, Yaru Bai, Xianxiang Wu, Si Luan, Xiurong Ren, Liwen Wang, Jinhua She, Zhanfei Xiao, Bin Du, Guanhua affil: General Clinical Research Center, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University, Ordos 017000, China sug: subj: Health Screening COVID-19 Drug Therapy Minocycline Therapeutic Use Minocycline Pharmacodynamics Peptide Hydrolases Drug Effects Coronavirus Drug Effects Treatment Outcomes Animal Studies In Vitro Studies Molecular Docking Simulation Molecular Structure Ribosomal Proteins Drug Effects RNA Drug Effects Descriptive Statistics Peptide Hydrolases Analysis Comparative Studies Chemical and Pharmacologic Phenomena Funding Source ab: What Is Known and Objective. Novel coronavirus disease (COVID-19) is still ravaging globally since its first discovery in 2019. With the continuous emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) mutant strains, therapeutic entities are still needed to be discovered. This study was to explore SARS-CoV-2 inhibitors and therapeutic entities for COVID-19. Methods. Based on Lipinski's rule of 5, a small-scale "old" drug database (clinical drugs being used in Ordos Central Hospital) was established, and in silico screening of Mpro inhibitors was conducted. Binding affinity and interaction as well as structure-affinity relationship were analyzed. Furthermore, molecular dynamic (MD) simulation of the selected drugs was performed to understand the conformational changes in docked complex. In vitro Mpro inhibition tests were performed according to established methods. Finally, literature review of potential "old" drug for the treatment of COVID-19 was conducted. Results and Discussion. The antibiotic minocycline, an inhibitor of bacterial ribosomal RNA, was screened out which showed the highest binding affinity (−9.6 kcal/mol). Beside the hydrogen bond with Cys145 and hydrophobic interactions, minocycline formed a pi-cation with His41, which strongly supported minocycline as a Michael addition acceptor to bind with the catalytic site of Mpro. MD simulation results show that minocycline displayed less conformational changes. The structure-affinity relationship was summarized based on minocycline analogs, and minocycline showed in vitro Mpro inhibitory activity with IC50 of 5 mM. More importantly, the literature review found that minocycline had both in vitro and in vivo broad-spectrum antiviral as well as anti-inflammatory activities, and the levels of a broad spectrum of biological markers during minocycline administration were opposed to those of COVID-19 conditions (both severe and nonsevere). What is New and Conclusion. Minocycline deserves an adjunctive therapeutic option for COVID-19 condition (both severe and nonsevere). This study shed a new light on drug-repurposing strategy for the viral disease. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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