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

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 a...

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Autores principales: Kreiser, Topaz, Zaguri, Dor, Sachdeva, Shreya, Zamostiano, Rachel, Mograbi, Josef, Segal, Daniel, Bacharach, Eran, Gazit, Ehud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955458/
https://www.ncbi.nlm.nih.gov/pubmed/35337174
http://dx.doi.org/10.3390/ph15030377
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author Kreiser, Topaz
Zaguri, Dor
Sachdeva, Shreya
Zamostiano, Rachel
Mograbi, Josef
Segal, Daniel
Bacharach, Eran
Gazit, Ehud
author_facet Kreiser, Topaz
Zaguri, Dor
Sachdeva, Shreya
Zamostiano, Rachel
Mograbi, Josef
Segal, Daniel
Bacharach, Eran
Gazit, Ehud
author_sort Kreiser, Topaz
collection PubMed
description 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.
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spelling pubmed-89554582022-03-26 Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions Kreiser, Topaz Zaguri, Dor Sachdeva, Shreya Zamostiano, Rachel Mograbi, Josef Segal, Daniel Bacharach, Eran Gazit, Ehud Pharmaceuticals (Basel) Article 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. MDPI 2022-03-20 /pmc/articles/PMC8955458/ /pubmed/35337174 http://dx.doi.org/10.3390/ph15030377 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kreiser, Topaz
Zaguri, Dor
Sachdeva, Shreya
Zamostiano, Rachel
Mograbi, Josef
Segal, Daniel
Bacharach, Eran
Gazit, Ehud
Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions
title Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions
title_full Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions
title_fullStr Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions
title_full_unstemmed Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions
title_short Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions
title_sort inhibition of respiratory rna viruses by a composition of ionophoric polyphenols with metal ions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955458/
https://www.ncbi.nlm.nih.gov/pubmed/35337174
http://dx.doi.org/10.3390/ph15030377
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