دورية أكاديمية
On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine.
| العنوان: | On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine. |
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| المؤلفون: | Dahal S; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada., Clayton K; Department of Pathology, University of Massachusetts Medical School , Worcester, Massachusetts, USA., Cabral T; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada., Cheng R; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada., Jahanshahi S; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada.; Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada., Ahmed C; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada., Koirala A; Department of Molecular and Cellular Biology, Baylor College of Medicine , Houston, Texas, USA.; Dan L. Duncan Cancer Comprehensive Center, Baylor College of Medicine , Houston, Texas, USA., Villasmil Ocando A; Ragon Institute of MGH, MIT and Harvard , Cambridge, Massachusetts, USA., Malty R; Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada.; Research and Innovation Centre, Department of Biochemistry, University of Regina , Regina, Saskatchewan, Canada., Been T; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada., Hernandez J; Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada., Mangos M; Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada., Shen D; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada., Babu M; Research and Innovation Centre, Department of Biochemistry, University of Regina , Regina, Saskatchewan, Canada., Calarco J; Department of Cell and Systems Biology, University of Toronto , Toronto, Ontario, Canada., Chabot B; Department of Microbiology and Infectious Diseases, Université de Sherbrooke , Sherbrooke, Quebec, Canada., Attisano L; Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada., Houry WA; Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada.; Department of Chemistry, University of Toronto , Toronto, Ontario, Canada., Cochrane A; Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada. |
| المصدر: | Journal of virology [J Virol] 2023 Oct 31; Vol. 97 (10), pp. e0039623. Date of Electronic Publication: 2023 Sep 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Antiviral Agents*/pharmacology , Antiviral Agents*/therapeutic use , Coronavirus*/drug effects , Coronavirus*/physiology , Harmine*/pharmacology , Harmine*/therapeutic use , HIV-1*/drug effects , HIV-1*/physiology, Humans ; Coronavirus Infections/drug therapy ; Virus Replication/drug effects |
| مستخلص: | Importance: This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple SARS-CoV-2 variants) replication. Harmine inhibits HIV-1 protein expression and reduces accumulation of HIV-1 RNAs in both cell lines and primary CD4 + T cells. Harmine also suppresses coronavirus replication post-viral entry by preferentially reducing coronavirus sub-genomic RNA accumulation. By focusing on host factors rather than viral targets, our study offers a novel approach to combating viral infections that is effective against a range of unrelated viruses. Moreover, at doses required to inhibit virus replication, harmine had limited toxicity and minimal effect on the host transcriptome. These findings support the viability of targeting host cellular processes as a means of developing broad-spectrum anti-virals. Competing Interests: The authors declare no conflict of interest. |
| معلومات مُعتمدة: | Canadian Foundation for AIDS Research (CANFAR); PJT-178165 Gouvernement du Canada | Canadian Institutes of Health Research (IRSC); PJT-173491 Gouvernement du Canada | Canadian Institutes of Health Research (IRSC); PJT-165966 Gouvernement du Canada | Canadian Institutes of Health Research (IRSC); VR2-172717) Gouvernement du Canada | Canadian Institutes of Health Research (IRSC); Gouvernement du Canada | Canadian Institutes of Health Research (IRSC); PRMF2020-007 PRiME fellowship; PRMF2021-005 PRiME fellowship |
| فهرسة مساهمة: | Keywords: HIV-1; RNA processing; SR kinase; coronaviruses; inhibitors |
| المشرفين على المادة: | 0 (Antiviral Agents) 4FHH5G48T7 (Harmine) |
| تواريخ الأحداث: | Date Created: 20230914 Date Completed: 20240110 Latest Revision: 20240212 |
| رمز التحديث: | 20240212 |
| مُعرف محوري في PubMed: | PMC10617549 |
| DOI: | 10.1128/jvi.00396-23 |
| PMID: | 37706687 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
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| DOI: | 10.1128/jvi.00396-23 |