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.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
de Freitas CS,Rocha MEN,Sacramento CQ,Marttorelli A,Ferreira AC,Rocha N,de Oliveira AC,de Oliveira Gomes AM,Dos Santos PS,da Silva EO,da Costa JP,de Lima Moreira D,Bozza PT,Silva JL,Barroso SPC,Souza TMLdoi
10.2174/1568026620666191219150738subject
Has Abstractpub_date
2020-01-01 00:00:00pages
111-120issue
2eissn
1568-0266issn
1873-4294pii
CTMC-EPUB-103096journal_volume
20pub_type
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