Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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
_version_ 1783708287648137216
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
work_keys_str_mv AT panagiotopoulosathanasios pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT tselioumelpomeni pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT karakasiliotisioannis pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT kotzampasidanaimaria pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT daskalakisvangelis pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT kesesidisnikolaos pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT notasgeorge pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT lionischristos pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT kampamarilena pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT pirintsosstergios pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT sourvinosgeorge pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein
AT castanaselias pcymeneimpairssarscov2andinfluenzaah1n1viralreplicationinsilicopredictedinteractionwithsarscov2nucleocapsidproteinandh1n1nucleoprotein