On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine

Subha Dahal; Kiera Clayton; Tyler Cabral; Ran Cheng; Shahrzad Jahanshahi; Choudhary Ahmed; Amrit Koirala; Alonso Villasmil Ocando; Ramy Malty; Terek Been; Javier Hernandez; Maria Mangos; David Shen; Mohan Babu; John Calarco; Benoit Chabot; Liliana Attisano; Walid A Houry; Alan Cochrane

doi:10.1128/jvi.00396-23

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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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On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine

Subha Dahal, Kiera Clayton, Tyler Cabral, Ran Cheng, Shahrzad Jahanshahi, Choudhary Ahmed, Amrit Koirala, Alonso Villasmil Ocando, Ramy Malty, Terek Been, …

Journal of virology, Vol.97(10), p.e0039623

31/10/2023

DOI: https://doi.org/10.1128/jvi.00396-23

PMID: 37706687

Résumé

Antiviral Agents - pharmacology

Antiviral Agents - therapeutic use

Coronavirus - drug effects

Coronavirus - physiology

Coronavirus Infections - drug therapy

Harmine - pharmacology

Harmine - therapeutic use

HIV-1 - drug effects

HIV-1 - physiology

Humans

Virus Replication - drug effects

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.

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Détails

Titre: On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine
Créateurs - sans rôle: Subha Dahal - Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
Kiera Clayton - Department of Pathology, University of Massachusetts Medical School , Worcester, Massachusetts, USA
Tyler Cabral - Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
Ran Cheng - Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
Shahrzad Jahanshahi - Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada
Choudhary Ahmed - Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
Amrit Koirala - Dan L. Duncan Cancer Comprehensive Center, Baylor College of Medicine , Houston, Texas, USA
Alonso Villasmil Ocando - Ragon Institute of MGH, MIT and Harvard , Cambridge, Massachusetts, USA
Ramy Malty - Research and Innovation Centre, Department of Biochemistry, University of Regina , Regina, Saskatchewan, Canada
Terek Been - Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
Javier Hernandez - Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada
Maria Mangos - Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada
David Shen - Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
Mohan Babu - Research and Innovation Centre, Department of Biochemistry, University of Regina , Regina, Saskatchewan, Canada
John Calarco - Department of Cell and Systems Biology, University of Toronto , Toronto, Ontario, Canada
Benoit Chabot - Department of Microbiology and Infectious Diseases, Université de Sherbrooke , Sherbrooke, Quebec, Canada
Liliana Attisano - Department of Biochemistry, University of Toronto , Toronto, Ontario, Canada
Walid A Houry - University of Toronto
Alan Cochrane - Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
Détails de publication: Journal of virology, Vol.97(10), p.e0039623
Note de subvention: 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
Identifiants: 99155841109311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article