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p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein
Therapeutic regimens for the COVID‐19 pandemics remain unmet. In this line, repurposing of existing drugs against known or predicted SARS‐CoV‐2 protein actions have been advanced, while natural products have also been tested. Here, we propose that p‐cymene, a natural monoterpene, can act as a potent...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204097/ https://www.ncbi.nlm.nih.gov/pubmed/34128351 http://dx.doi.org/10.1002/prp2.798 |
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author | Panagiotopoulos, Athanasios Tseliou, Melpomeni Karakasiliotis, Ioannis Kotzampasi, Danai‐Maria Daskalakis, Vangelis Kesesidis, Nikolaos Notas, George Lionis, Christos Kampa, Marilena Pirintsos, Stergios Sourvinos, George Castanas, Elias |
author_facet | Panagiotopoulos, Athanasios Tseliou, Melpomeni Karakasiliotis, Ioannis Kotzampasi, Danai‐Maria Daskalakis, Vangelis Kesesidis, Nikolaos Notas, George Lionis, Christos Kampa, Marilena Pirintsos, Stergios Sourvinos, George Castanas, Elias |
author_sort | Panagiotopoulos, Athanasios |
collection | PubMed |
description | Therapeutic regimens for the COVID‐19 pandemics remain unmet. In this line, repurposing of existing drugs against known or predicted SARS‐CoV‐2 protein actions have been advanced, while natural products have also been tested. Here, we propose that p‐cymene, a natural monoterpene, can act as a potential novel agent for the treatment of SARS‐CoV‐2‐induced COVID‐19 and other RNA‐virus‐induced diseases (influenza, rabies, Ebola). We show by extensive molecular simulations that SARS‐CoV‐2 C‐terminal structured domain contains a nuclear localization signal (NLS), like SARS‐CoV, on which p‐cymene binds with low micromolar affinity, impairing nuclear translocation of this protein and inhibiting viral replication, as verified by preliminary in vitro experiments. A similar mechanism may occur in other RNA‐viruses (influenza, rabies and Ebola), also verified in vitro for influenza, by interaction of p‐cymene with viral nucleoproteins, and structural modification of their NLS site, weakening its interaction with importin A. This common mechanism of action renders therefore p‐cymene as a possible antiviral, alone, or in combination with other agents, in a broad spectrum of RNA viruses, from SARS‐CoV‐2 to influenza A infections. |
format | Online Article Text |
id | pubmed-8204097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82040972021-06-16 p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein Panagiotopoulos, Athanasios Tseliou, Melpomeni Karakasiliotis, Ioannis Kotzampasi, Danai‐Maria Daskalakis, Vangelis Kesesidis, Nikolaos Notas, George Lionis, Christos Kampa, Marilena Pirintsos, Stergios Sourvinos, George Castanas, Elias Pharmacol Res Perspect Original Articles Therapeutic regimens for the COVID‐19 pandemics remain unmet. In this line, repurposing of existing drugs against known or predicted SARS‐CoV‐2 protein actions have been advanced, while natural products have also been tested. Here, we propose that p‐cymene, a natural monoterpene, can act as a potential novel agent for the treatment of SARS‐CoV‐2‐induced COVID‐19 and other RNA‐virus‐induced diseases (influenza, rabies, Ebola). We show by extensive molecular simulations that SARS‐CoV‐2 C‐terminal structured domain contains a nuclear localization signal (NLS), like SARS‐CoV, on which p‐cymene binds with low micromolar affinity, impairing nuclear translocation of this protein and inhibiting viral replication, as verified by preliminary in vitro experiments. A similar mechanism may occur in other RNA‐viruses (influenza, rabies and Ebola), also verified in vitro for influenza, by interaction of p‐cymene with viral nucleoproteins, and structural modification of their NLS site, weakening its interaction with importin A. This common mechanism of action renders therefore p‐cymene as a possible antiviral, alone, or in combination with other agents, in a broad spectrum of RNA viruses, from SARS‐CoV‐2 to influenza A infections. John Wiley and Sons Inc. 2021-06-14 /pmc/articles/PMC8204097/ /pubmed/34128351 http://dx.doi.org/10.1002/prp2.798 Text en © 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Panagiotopoulos, Athanasios Tseliou, Melpomeni Karakasiliotis, Ioannis Kotzampasi, Danai‐Maria Daskalakis, Vangelis Kesesidis, Nikolaos Notas, George Lionis, Christos Kampa, Marilena Pirintsos, Stergios Sourvinos, George Castanas, Elias p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein |
title | p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein |
title_full | p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein |
title_fullStr | p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein |
title_full_unstemmed | p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein |
title_short | p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein |
title_sort | p‐cymene impairs sars‐cov‐2 and influenza a (h1n1) viral replication: in silico predicted interaction with sars‐cov‐2 nucleocapsid protein and h1n1 nucleoprotein |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204097/ https://www.ncbi.nlm.nih.gov/pubmed/34128351 http://dx.doi.org/10.1002/prp2.798 |
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