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

by Selleckchem | Jan 11 2024

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.

Comments:

The exploration of repurposed drugs and novel therapeutic avenues for combating SARS-CoV-2 is crucial in the ongoing fight against the pandemic. The potential repurposing of a veterinary antibiotic like the FDA-approved polyether ionophore for treating SARS-CoV-2 infections is intriguing, especially when supported by in vitro and in vivo studies.

The distinct advantage of ionophores lies in their demonstrated therapeutic effects at very low concentrations, as indicated by their selectivity index values. Their ability to target various viral components, including both structural and non-structural proteins, as well as host-cell factors, showcases a promising multi-faceted approach to inhibiting SARS-CoV-2.

Moreover, the synergy observed between ionophores and Zn2+ supplementation in enhancing their antiviral activity adds another layer of interest to this therapeutic strategy. This combination approach could potentially offer more effective treatment options for COVID-19 patients.

The review highlighting the anti-SARS-CoV-2 potential of selective ionophores like monensin, salinomycin, maduramicin, CP-80,219, nanchangmycin, narasin, X-206, and valinomycin provides a comprehensive overview of their molecular targets. Understanding how these ionophores interact with the virus and host cells can pave the way for targeted therapies and further investigation into their potential for human use.

While this direction shows promise, extensive research and clinical trials are essential to validate the safety and efficacy of these ionophores and their combinations with Zn2+ as a viable treatment for COVID-19. Collaborative efforts in this area could potentially lead to innovative and more effective therapeutic options against SARS-CoV-2 and other viral infections.