Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro.
Identifieur interne : 000755 ( Main/Corpus ); précédent : 000754; suivant : 000756Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro.
Auteurs : Esben B. Svenningsen ; Jacob Thyrsted ; Julia Blay-Cadanet ; Han Liu ; Shaoquan Lin ; Jaime Moyano-Villameriel ; David Olagnier ; Manja Idorn ; S Ren R. Paludan ; Christian K. Holm ; Thomas B. PoulsenSource :
- Antiviral research [ 1872-9096 ] ; 2021.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Anti-Bacterial Agents, Antiviral Agents, Ethers, Cyclic, Ionophores.
- drug effects : SARS-CoV-2, Virus Replication.
- drug therapy : COVID-19.
- Animals, Chlorocebus aethiops, Humans, Vero Cells.
Abstract
Pandemic spread of emerging human pathogenic viruses, such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, e.g. through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.
DOI: 10.1016/j.antiviral.2020.104988
PubMed: 33248195
PubMed Central: PMC7687369
Links to Exploration step
pubmed:33248195Le document en format XML
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<term>Antiviral Agents (pharmacology)</term>
<term>COVID-19 (drug therapy)</term>
<term>Chlorocebus aethiops (MeSH)</term>
<term>Ethers, Cyclic (pharmacology)</term>
<term>Humans (MeSH)</term>
<term>Ionophores (pharmacology)</term>
<term>SARS-CoV-2 (drug effects)</term>
<term>Vero Cells (MeSH)</term>
<term>Virus Replication (drug effects)</term>
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<term>Antiviral Agents</term>
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<term>Virus Replication</term>
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<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term>
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<front><div type="abstract" xml:lang="en">Pandemic spread of emerging human pathogenic viruses, such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, e.g. through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.</div>
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<Abstract><AbstractText>Pandemic spread of emerging human pathogenic viruses, such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, e.g. through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.</AbstractText>
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