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SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral

SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus,...

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Autores principales: Jimenez-Aleman, Guillermo H., Castro, Victoria, Londaitsbehere, Addis, Gutierrez-Rodríguez, Marta, Garaigorta, Urtzi, Solano, Roberto, Gastaminza, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538351/
https://www.ncbi.nlm.nih.gov/pubmed/34681272
http://dx.doi.org/10.3390/ph14101048
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author Jimenez-Aleman, Guillermo H.
Castro, Victoria
Londaitsbehere, Addis
Gutierrez-Rodríguez, Marta
Garaigorta, Urtzi
Solano, Roberto
Gastaminza, Pablo
author_facet Jimenez-Aleman, Guillermo H.
Castro, Victoria
Londaitsbehere, Addis
Gutierrez-Rodríguez, Marta
Garaigorta, Urtzi
Solano, Roberto
Gastaminza, Pablo
author_sort Jimenez-Aleman, Guillermo H.
collection PubMed
description SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its infectivity in a dose- and time-dependent manner. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against enveloped RNA viral pathogens such as HCV, West Nile, and other coronaviruses. Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, which together with its previous use in photoactivable cancer therapy in humans, suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.
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spelling pubmed-85383512021-10-24 SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral Jimenez-Aleman, Guillermo H. Castro, Victoria Londaitsbehere, Addis Gutierrez-Rodríguez, Marta Garaigorta, Urtzi Solano, Roberto Gastaminza, Pablo Pharmaceuticals (Basel) Article SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its infectivity in a dose- and time-dependent manner. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against enveloped RNA viral pathogens such as HCV, West Nile, and other coronaviruses. Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, which together with its previous use in photoactivable cancer therapy in humans, suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2. MDPI 2021-10-15 /pmc/articles/PMC8538351/ /pubmed/34681272 http://dx.doi.org/10.3390/ph14101048 Text en © 2021 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
Jimenez-Aleman, Guillermo H.
Castro, Victoria
Londaitsbehere, Addis
Gutierrez-Rodríguez, Marta
Garaigorta, Urtzi
Solano, Roberto
Gastaminza, Pablo
SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral
title SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral
title_full SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral
title_fullStr SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral
title_full_unstemmed SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral
title_short SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral
title_sort sars-cov-2 fears green: the chlorophyll catabolite pheophorbide a is a potent antiviral
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538351/
https://www.ncbi.nlm.nih.gov/pubmed/34681272
http://dx.doi.org/10.3390/ph14101048
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