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Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus

Naturally occurring plant flavonoids are a promising class of antiviral agents to inhibit African swine fever virus (ASFV), which causes highly fatal disease in pigs and is a major threat to the swine industry. Currently known flavonoids with anti-ASFV activity demonstrate a wide range of antiviral...

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Autores principales: Arabyan, Erik, Hakobyan, Astghik, Hakobyan, Tamara, Grigoryan, Rafaella, Izmailyan, Roza, Avetisyan, Aida, Karalyan, Zaven, Jackman, Joshua A., Ferreira, Fernando, Elrod, Charles C., Zakaryan, Hovakim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567988/
https://www.ncbi.nlm.nih.gov/pubmed/34745038
http://dx.doi.org/10.3389/fmicb.2021.736780
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author Arabyan, Erik
Hakobyan, Astghik
Hakobyan, Tamara
Grigoryan, Rafaella
Izmailyan, Roza
Avetisyan, Aida
Karalyan, Zaven
Jackman, Joshua A.
Ferreira, Fernando
Elrod, Charles C.
Zakaryan, Hovakim
author_facet Arabyan, Erik
Hakobyan, Astghik
Hakobyan, Tamara
Grigoryan, Rafaella
Izmailyan, Roza
Avetisyan, Aida
Karalyan, Zaven
Jackman, Joshua A.
Ferreira, Fernando
Elrod, Charles C.
Zakaryan, Hovakim
author_sort Arabyan, Erik
collection PubMed
description Naturally occurring plant flavonoids are a promising class of antiviral agents to inhibit African swine fever virus (ASFV), which causes highly fatal disease in pigs and is a major threat to the swine industry. Currently known flavonoids with anti-ASFV activity demonstrate a wide range of antiviral mechanisms, which motivates exploration of new antiviral candidates within this class. The objective of this study was to determine whether other flavonoids may significantly inhibit ASFV infection in vitro. We performed a cell-based library screen of 90 flavonoids. Our screening method allowed us to track the development of virus-induced cytopathic effect by MTT in the presence of tested flavonoids. This screening method was shown to be robust for hit identification, with an average Z-factor of 0.683. We identified nine compounds that inhibit ASFV Ba71V strain in Vero cells. Among them, kaempferol was the most potent and exhibited dose-dependent inhibition, which occurred through a virostatic effect. Time-of-addition studies revealed that kaempferol acts on the entry and post-entry stages of the ASFV replication cycle and impairs viral protein and DNA synthesis. It was further identified that kaempferol induces autophagy in ASFV-infected Vero cells, which is related to its antiviral activity and could be partially abrogated by the addition of an autophagy inhibitor. Kaempferol also exhibited dose-dependent inhibition of a highly virulent ASFV Arm/07 isolate in porcine macrophages. Together, these findings support that kaempferol is a promising anti-ASFV agent and has a distinct antiviral mechanism compared to other anti-ASFV flavonoids.
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spelling pubmed-85679882021-11-05 Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus Arabyan, Erik Hakobyan, Astghik Hakobyan, Tamara Grigoryan, Rafaella Izmailyan, Roza Avetisyan, Aida Karalyan, Zaven Jackman, Joshua A. Ferreira, Fernando Elrod, Charles C. Zakaryan, Hovakim Front Microbiol Microbiology Naturally occurring plant flavonoids are a promising class of antiviral agents to inhibit African swine fever virus (ASFV), which causes highly fatal disease in pigs and is a major threat to the swine industry. Currently known flavonoids with anti-ASFV activity demonstrate a wide range of antiviral mechanisms, which motivates exploration of new antiviral candidates within this class. The objective of this study was to determine whether other flavonoids may significantly inhibit ASFV infection in vitro. We performed a cell-based library screen of 90 flavonoids. Our screening method allowed us to track the development of virus-induced cytopathic effect by MTT in the presence of tested flavonoids. This screening method was shown to be robust for hit identification, with an average Z-factor of 0.683. We identified nine compounds that inhibit ASFV Ba71V strain in Vero cells. Among them, kaempferol was the most potent and exhibited dose-dependent inhibition, which occurred through a virostatic effect. Time-of-addition studies revealed that kaempferol acts on the entry and post-entry stages of the ASFV replication cycle and impairs viral protein and DNA synthesis. It was further identified that kaempferol induces autophagy in ASFV-infected Vero cells, which is related to its antiviral activity and could be partially abrogated by the addition of an autophagy inhibitor. Kaempferol also exhibited dose-dependent inhibition of a highly virulent ASFV Arm/07 isolate in porcine macrophages. Together, these findings support that kaempferol is a promising anti-ASFV agent and has a distinct antiviral mechanism compared to other anti-ASFV flavonoids. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8567988/ /pubmed/34745038 http://dx.doi.org/10.3389/fmicb.2021.736780 Text en Copyright © 2021 Arabyan, Hakobyan, Hakobyan, Grigoryan, Izmailyan, Avetisyan, Karalyan, Jackman, Ferreira, Elrod and Zakaryan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Arabyan, Erik
Hakobyan, Astghik
Hakobyan, Tamara
Grigoryan, Rafaella
Izmailyan, Roza
Avetisyan, Aida
Karalyan, Zaven
Jackman, Joshua A.
Ferreira, Fernando
Elrod, Charles C.
Zakaryan, Hovakim
Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus
title Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus
title_full Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus
title_fullStr Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus
title_full_unstemmed Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus
title_short Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus
title_sort flavonoid library screening reveals kaempferol as a potential antiviral agent against african swine fever virus
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567988/
https://www.ncbi.nlm.nih.gov/pubmed/34745038
http://dx.doi.org/10.3389/fmicb.2021.736780
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