2. Academic Validation
  3. Agathisflavone, a Biflavonoid from Anacardium occidentale L., Inhibits Influenza Virus Neuraminidase

Agathisflavone, a Biflavonoid from Anacardium occidentale L., Inhibits Influenza Virus Neuraminidase

  • Curr Top Med Chem. 2020;20(2):111-120. doi: 10.2174/1568026620666191219150738.
Caroline S de Freitas 1 2,  Marco E N Rocha 1 2 3,  Carolina Q Sacramento 1 2,  Andressa Marttorelli 1 2,  André C Ferreira 1 2,  Natasha Rocha 1 2,  Andrea Cheble de Oliveira 4 5,  Andre Marco de Oliveira Gomes 4 5,  Patrícia Souza Dos Santos 4 5,  Edilene Oliveira da Silva 5 6,  Josineide Pantoja da Costa 5 6,  Davyson de Lima Moreira 3,  Patrícia T Bozza 1,  Jerson L Silva 4 5,  Shana Priscila Coutinho Barroso 4 5 7,  Thiago Moreno L Souza 1 2
Affiliations

Affiliations

  • 1 Laboratorio de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundacao Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.
  • 2 National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
  • 3 Laboratório de Química de Produtos Naturais 5, Farmanguinhos, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
  • 4 Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • 5 Instituto Nacional de Ciencia e Tecnologia de Biologia Estrutural e Bioimagem, Brazil.
  • 6 Universidade Federal do Pará, Instituto de Ciências Biológicas, Laboratório de Biologia Estrutural, Belém, Pará, Brazil.
  • 7 Instituto de Pesquisas Biomédicas, Hospital Naval Marcílio Dias, Marinha do Brasil, Brazil.
PMID: 31854280 DOI: 10.2174/1568026620666191219150738
Abstract

Background: Neuraminidase inhibitors (NAIs) are the only class of antivirals in clinical use against Influenza Virus approved worldwide. However, approximately 1-3% of circulating strains present resistance mutations to oseltamivir (OST), the most used NAI. Therefore, it is important to catalogue new molecules to inhibit Influenza Virus, especially OST-resistant strains. Natural Products from tropical Plants used for human consumption represent a worthy class of substances. Their use could be stimulated in resource-limited setting where the access to expensive Antiviral therapies is restricted.

Methods: We evaluated the anti-influenza virus activity of agathisflavone derived from Anacardium occidentale L.

Results: The neuraminidase (NA) activity of wild-type and OST-resistant Influenza Virus was inhibited by agathisflavone, with IC50 values ranging from 20 to 2.0 µM, respectively. Agathisflavone inhibited Influenza Virus replication with EC50 of 1.3 µM. Sequential passages of the virus in the presence of agathisflavone revealed the emergence of mutation R249S, A250S and R253Q in the NA gene. These changes are outside the OST binding region, meaning that agathisflavone targets this viral Enzyme at a region different than conventional NAIs.

Conclusion: Altogether our data suggest that agathisflavone has a promising chemical structure for the development of anti-influenza drugs.

Keywords

Agathisflavone; Anacardiaceae; Anacardium occidentale L; Antiviral; Flavonoid; Influenza..

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