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Repurposing Polyether Ionophores as a New-Class of Anti-SARS-Cov-2 Agents as Adjunct Therapy

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Abstract

The emergence of SARS-CoV-2 and its variants have posed a significant threat to humankind in tackling the viral spread. Furthermore, currently repurposed drugs and frontline antiviral agents have failed to cure severe ongoing infections effectively. This insufficiency has fuelled research for potent and safe therapeutic agents to treat COVID-19. Nonetheless, various vaccine candidates have displayed a differential efficacy and need for repetitive dosing. The FDA-approved polyether ionophore veterinary antibiotic for treating coccidiosis has been repurposed for treating SARS-CoV-2 infection (as shown by both in vitro and in vivo studies) and other deadly human viruses. Based on selectivity index values, ionophores display therapeutic effects at sub-nanomolar concentrations and exhibit selective killing ability. They act on different viral targets (structural and non-structural proteins), host-cell components leading to SARS-CoV-2 inhibition, and their activity is further enhanced by Zn2+ supplementation. This review summarizes the anti-SARS-CoV-2 potential and molecular viral targets of selective ionophores like monensin, salinomycin, maduramicin, CP-80,219, nanchangmycin, narasin, X-206 and valinomycin. Ionophore combinations with Zn2+ are a new therapeutic strategy that warrants further investigation for possible human benefits.

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Acknowledgements

The V.R. lab is supported by the research grant from Department of Science & Technology (DST), INSPIRE-Faculty Project (DST/INSPIRE/04/2018/003541), Ministry of Science and Technology, Government of India.

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  1. Keerthana Gurukkalot and Vinoth Rajendran equally contributed to this work.

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  1. Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, 605014, India

    Keerthana Gurukkalot & Vinoth Rajendran

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KG and VR contributed equally towards the literature survey, data interpretation and preparation of the figures. VR contributed to the overall supervision, design of the review, critical analysis of the intellectual content, revision of the manuscript and funding acquisition. All authors read and approved the final version of the manuscript.

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Correspondence to Vinoth Rajendran.

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Gurukkalot, K., Rajendran, V. Repurposing Polyether Ionophores as a New-Class of Anti-SARS-Cov-2 Agents as Adjunct Therapy. Curr Microbiol 80, 273 (2023). https://doi.org/10.1007/s00284-023-03366-1

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