Virtual Screening of Citrus Flavonoid Tangeretin: A Promising Pharmacological Tool for the Treatment and Prevention of Zika fever and COVID-19

Abstract

It is of great importance for the pharmaceutical industry to find therapeutic substances extracted from natural sources, which are abundant, obtained with low costs and presenting the antiviral potential for the treatment of Zika virus (ZIKV) and COVID-19. Tangeretin (TAN) is a citrus polymethoxyflavone from Citrus reticulata peel oil with known antiviral activities, whose physico-chemical properties are not reported. The present study aimed to investigate by a theoretical screening of electronic, structural properties and pharmacodynamic and pharmacokinetic parameters that characterize TAN as a therapeutic drug in the treatment and prevention of zika fever and COVID-19. The molecule reached its minimum energy-forming state of [Formula: see text]795.85747[Formula: see text]kJ/mol and the HOMO and LUMO boundary orbitals reactivity descriptors suggest that the compound is stable and does not tend to be reactive in intermolecular interactions. The ligand connects to the NS1 ZIKV receptor with strong H-bond interactions, also connects with the NS5 ZIKV receptor in a competitive effect with the SAM inhibitor and acts in a supplementary effect with the N3 inhibitor and the BRT drug in the Mpro SARS-CoV-2 receptor. The properties of ADMET shows that the compound suffers few amounts of drug alterations because it inhibits the metabolic enzymes CYP2C9 and CYP3A4 and penetrates the central nervous system, without accumulation of drug residues in the blood or in the lumen in the gastrointestinal tract, without risk of toxicity to the patient. With the results obtained, it is possible to identify TAN as a promising pharmacological tool for the treatment and prevention of Zika fever and COVID-19.