Article
Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
Registro en:
CHAVES, Otávio Augusto et al. Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases. International Journal of Biological Macromolecules, v. 222, Part A, p. 1015-1026, Dec. 2022.
0141-8130
10.1016/j.ijbiomac.2022.09.204
Autor
Chaves, Otávio Augusto
Lima, Carlyle Ribeiro
Fintelman-Rodrigues, Natalia
Sacramento, Carolina Q.
Freitas, Caroline S. de
Vazquez, Leonardo
Temerozo, Jairo R.
Rocha, Marco E.N.
Dias, Suelen S. G.
Carels, Nicolas
Bozza, Patrícia T.
Faria Neto, Hugo Caire Castro
Souza, Thiago Moreno L.
Resumen
Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, chemical structures endowed with anti-SARS-CoV-2 activity are important for continuous antiviral development and natural products represent a fruitful source of substances with biological activity. In the present study, agathisflavone (AGT), a biflavonoid from Anacardium occidentale was investigated as a candidate anti-SARS-CoV-2 compound. In silico and enzymatic analysis indicated that AGT may target mainly the viral main protease (Mpro) and not the papain-like protease (PLpro) in a non-competitive way. Cell-based assays in type II pneumocytes cell lineage (Calu-3) showed that SARS-CoV-2 is more susceptible to AGT than to apigenin (APG, monomer of AGT), in a dose-dependent manner, with an EC50 of 4.23 ± 0.21 μM and CC50 of 61.3 ± 0.1 μM and with a capacity to inhibit the level of pro-inflammatory mediator tumor necrosis factor-alpha (TNF-α). These results configure AGT as an interesting chemical scaffold for the development of novel semisynthetic antivirals against SARS-CoV-2.