Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)
Mem. Inst. Oswaldo Cruz
; 115: e200207, 2020. tab, graf
Artigo
em Inglês
| LILACS, Sec. Est. Saúde SP
| ID: biblio-1135237
Biblioteca responsável:
BR1.1
ABSTRACT
BACKGROUND Since the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) to be a pandemic infection, important severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (nsp) have been analysed as promising targets in virtual screening approaches. Among these proteins, 3-chymotrypsin-like cysteine protease (3CLpro), also named main protease, and the RNA-dependent RNA polymerase (RdRp), have been identified as fundamental targets due to its importance in the viral replication stages. OBJECTIVES To investigate, in silico, two of the most abundant flavonoid glycosides from Dysphania ambrosioides; a medicinal plant found in many regions of the world, along with some of the putative derivatives of these flavonoid glycosides in the human organism as potential inhibitors of the SARS-CoV-2 3CLpro and RdRp. METHODS Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives. FINDINGS Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins. Also, the importance of the hydrogen bond and π-based interactions was evidenced for the presumed active sites. MAIN CONCLUSIONS Overall, these results suggest that both flavonoid glycosides and their putative human metabolites can play a key role as inhibitors of the SARS-CoV-2 3CLpro and RdRp. Obviously, further researches, mainly in vitro and in vivo experiments, are necessary to certify the docking results reported here, as well as the adequate application of these substances. Furthermore, it is necessary to investigate the risks of D. ambrosioides as a phytomedicine for use against COVID-19.
Texto completo:
Disponível
Coleções:
Bases de dados nacionais
/
Brasil
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
Problema de saúde:
Meta 3.8 Atingir a cobertura universal de saúde
Base de dados:
LILACS
/
Sec. Est. Saúde SP
Assunto principal:
Flavonoides
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RNA Polimerase Dependente de RNA
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Proteínas não Estruturais Virais
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Betacoronavirus
/
Glicosídeos
Tipo de estudo:
Estudo prognóstico
Limite:
Humanos
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Ano de publicação:
2020
Tipo de documento:
Artigo
Instituição/País de afiliação:
Secretaria Municipal de Saúde/BR
/
Universidade Federal do Amazonas/BR
/
Universidade do Estado do Amazonas/BR