Flavonoids from Siparuna cristata as Potential Inhibitors of SARS-CoV-2 Replication

Abstract

The novel coronavirus SARS-CoV-2 has been affecting the world, causing severe pneumonia and acute respiratory syndrome, leading people to death. Therefore, the search for anti-SARS-CoV-2 compounds is pivotal for public health. Natural products may present sources of bioactive compounds; among them, flavonoids are known in literature for their antiviral activity. Siparuna species are used in Brazilian folk medicine for the treatment of colds and flu. This work describes the isolation of 3,3′,4′-tri-O-methyl-quercetin, 3,7,3′,4′-tetra-O-methyl-quercetin (retusin), and 3,7-di-O-methyl-kaempferol (kumatakenin) from the dichloromethane extract of leaves of Siparuna cristata (Poepp. & Endl.) A.DC., Siparunaceae, using high-speed countercurrent chromatography in addition to the investigation of their inhibitory effect against SARS-CoV-2 viral replication. Retusin and kumatakenin inhibited SARS-CoV-2 replication in Vero E6 and Calu-3 cells, with a selective index greater than lopinavir/ritonavir and chloroquine, used as control. Flavonoids and their derivatives may stand for target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

“…Using Vero E6 and Calu-3 cells, Leal et al recently demonstrated that Siparuna cristata-derived flavonols, 3,7-Di-O-methyl-kaempferol (kumatakenin) and 3,7,3 ,4 -Tetra-O-methyl-quercetin (retusin), inhibited the general viral replication of SARS-CoV-2 with very promising effective concentrations. Kumatakein showed EC50 values of 10 ± 0.7 and 0.3 ± 0.02 µM in Vero and Calu cells, respectively; similarly, retusin also exhibited promise with EC50s of 0.4 ± 0.05 and 0.6 ± 0.06 µM, respectively [140]. This activity was credited to inhibiting the viral 3CLpro and PLpro due to the authors' in silico investigations but was not confirmed experimentally.…”

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate Against SARS-CoV-2 Spike protein

“…Flavonoids are natural phytochemicals with antiviral properties which have been discovered to inhibit different targets of SARS-CoV [19] such as interfering with S protein and blocking enzymatic activities of viral proteases 3-chymotrypsin like proteases (3CL pro ), papain-like proteases (PL pro ). Previous research suggests that methylated avonoids, such as retusin, could be used as an antiviral or adjuvant medication in the treatment of COVID-19 [20]. Flavonoids are promising plant-derived chemicals for treating SARS-CoV-2 infection, either through direct antiviral effects or by controlling the host immunological response to viral infection [21].…”

The Role of Micronutrients to Support Immunity for COVID-19 Prevention

“…On the other hand, studies have observed that flavonoids contribute to the reduction of ROS accumulation decelerates the coronavirusactivated apoptotic signalling (Diniz et al 2020;Godinho et al 2021). In silico molecular docking studies have been performed to evaluate and validate the inhibitory effect of flavonoids based on the hydrogen-bonding distance between selected amino acid residues of the catalytic site from 3CLpro and PLpro SARS-CoV-2 proteases and flavonoids (Leal et al 2021).…”