Mem Inst Oswaldo Cruz, Rio de Janeiro, FAST TRACK
Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)
1Central Analítica, Centro de Apoio Multidisciplinar, Universidade Federal do Amazonas, Manaus, AM, Brazil
2Secretaria Municipal de Saúde, Prefeitura de Itabirito, Itabirito, MG, Brazil
3Departamento de Química, Universidade Federal do Amazonas, Manaus, AM, Brazil
4Grupo de Pesquisa em Metabolômica e Espectrometria de Massas, Universidade do Estado do Amazonas, Manaus, AM, Brazil
5Faculdade de Ciências Agrárias, Universidade Federal do Amazonas, Manaus, AM, Brazil
BACKGROUND Since the World Health Organization (WHO) declared COVID-19 to be a pandemic infection, important SARS-CoV-2 non-structural proteins (nsp) have been analised 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 the main targets.
OBJECTIVES To investigate, in silico, the main 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 analysis, 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 derivatives to be the best 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 research is 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.