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Article

Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions

1
The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv 6997801, Israel
2
Independent Researcher, Tel Aviv 6937940, Israel
3
Sagol Interdisciplinary School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel
4
BLAVATNIK CENTER for Drug Discovery, Tel Aviv University, Tel Aviv 6997801, Israel
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Alfredo Berzal-Herranz
Pharmaceuticals 2022, 15(3), 377; https://doi.org/10.3390/ph15030377
Received: 17 February 2022 / Revised: 16 March 2022 / Accepted: 17 March 2022 / Published: 20 March 2022
(This article belongs to the Section Biopharmaceuticals)
Controlling the infectivity of respiratory RNA viruses is critical, especially during the current SARS-CoV-2 pandemic. There is an unmet need for therapeutic agents that can reduce viral replication, preferably independent of the accumulation of viral mutations. Zinc ions have an apparent activity as modulators of intracellular viral RNA replication and thus, appear attractive in reducing viral RNA load and infectivity. However, the intracellular concentration of zinc is usually too low for achieving an optimal inhibitory effect. Various herbal polyphenols serve as excellent zinc ionophores with known antiviral properties. Here, we combined zinc picolinate with a collection of flavonoids, representing commonly used polyphenols. Copper was added to avoid ionic imbalance during treatment and to improve efficacy. Each component separately, as well as their combinations, did not interfere with the viability of cultured A549, H1299, or Vero cells in vitro as determined by MTT assay. The safe combinations were further evaluated to determine antiviral activity. Fluorescence-activated cell sorting and quantitative polymerase chain reaction were used to evaluate antiviral activity of the combinations. They revealed a remarkable (50–95%) decrease, in genome replication levels of a diverse group of respiratory RNA viruses, including the human coronavirus OC43 (HCoV-OC43; a betacoronavirus that causes the common cold), influenza A virus (IAV, strain A/Puerto Rico/8/34 H1N1), and human metapneumovirus (hMPV). Collectively, our results offer an orally bioavailable therapeutic approach that is non-toxic, naturally sourced, applicable to numerous RNA viruses, and potentially insensitive to new mutations and variants. View Full-Text
Keywords: zinc; polyphenols; flavonoids; antiviral; respiratory RNA viruses; replication inhibition zinc; polyphenols; flavonoids; antiviral; respiratory RNA viruses; replication inhibition
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MDPI and ACS Style

Kreiser, T.; Zaguri, D.; Sachdeva, S.; Zamostiano, R.; Mograbi, J.; Segal, D.; Bacharach, E.; Gazit, E. Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions. Pharmaceuticals 2022, 15, 377. https://doi.org/10.3390/ph15030377

AMA Style

Kreiser T, Zaguri D, Sachdeva S, Zamostiano R, Mograbi J, Segal D, Bacharach E, Gazit E. Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions. Pharmaceuticals. 2022; 15(3):377. https://doi.org/10.3390/ph15030377

Chicago/Turabian Style

Kreiser, Topaz, Dor Zaguri, Shreya Sachdeva, Rachel Zamostiano, Josef Mograbi, Daniel Segal, Eran Bacharach, and Ehud Gazit. 2022. "Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions" Pharmaceuticals 15, no. 3: 377. https://doi.org/10.3390/ph15030377

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