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Planta Med 2023; 89(10): 1001-1009
DOI: 10.1055/a-2058-3635
Biological and Pharmacological Activity
Original Papers

Antiviral Effect of Natural and Semisynthetic Diterpenoids against Adenovirus Infection in vitro

Juan Esteban Bidart
1   Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
2   Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
3   Instituto de Virología e Innovaciones Tecnológicas-IVIT, CICVyA, INTA-CONICET, Hurlingham, Argentina
,
Mariano Walter Pertino
4   Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Campus Lircay, Talca, Chile
,
Guillermo Schmeda-Hirschmann
4   Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Campus Lircay, Talca, Chile
,
Laura Edith Alché
1   Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
2   Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
,
Erina Petrera 
1   Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
2   Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
› Author AffiliationsSupported by: Universidad de Buenos Aires UBACyT 20020130100584
Supported by: Fondo para la Investigación Científica y Tecnológica PICT 2018–00733
Supported by: Consejo Nacional de Investigaciones Científicas y Técnicas PIP 20120100538
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Abstract

The emergence and re-emergence of viruses has highlighted the need to develop new broad-spectrum antivirals to mitigate human infections. Pursuing our search for new bioactive plant-derived molecules, we study several diterpene derivatives synthesized from jatropholones A and B and carnosic acid isolated from Jatropha isabellei and Rosmarinus officinalis, respectively. Here, we investigate the antiviral effect of the diterpenes against human adenovirus (HAdV-5) that causes several infections for which there is no approved antiviral therapy yet. Ten compounds are evaluated and none of them present cytotoxicity in A549 cells. Only compounds 2, 5 and 9 inhibit HAdV-5 replication in a concentration-dependent manner, without virucidal activity, whereas the antiviral action takes place after virus internalization. The expression of viral proteins E1A and Hexon is strongly inhibited by compounds 2 and 5 and, in a lesser degree, by compound 9. Since compounds 2, 5 and 9 prevent ERK activation, they might exert their antiviral action by interfering in the host cell functions required for virus replication. Besides, the compounds have an anti-inflammatory profile since they significantly inhibit the levels of IL-6 and IL-8 produced by THP-1 cells infected with HAdV-5 or with an adenoviral vector. In conclusion, diterpenes 2, 5 and 9 not only exert antiviral activity against adenovirus but also are able to restrain pro-inflammatory cytokines induced by the virus.

Key words

Jatropha isabellei - Rosmarinus officinalis. - diterpenes - antiviral - adenoviridae - Euphorbiaceae - Lamiaceae


Publication History

Received: 15 January 2023

Accepted after revision: 20 March 2023

Accepted Manuscript online:
20 March 2023

Article published online:
09 May 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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