Potential of Flavonoid-Inspired Phytomedicines against COVID-19

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 11; p. 2707
• Main Authors: Ngwa, Wilfred, Kumar, Rajiv, Thompson, Daryl, Lyerly, William, Moore, Roscoe, Reid, Terry-Elinor, Lowe, Henry, Toyang, Ngeh
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.06.2020; MDPI
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Animals; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Axl protein; Betacoronavirus - chemistry; Betacoronavirus - drug effects; Betacoronavirus - growth & development; Binding Sites; Bioavailability; Cathepsin L; Chloroquine - chemistry; Chloroquine - pharmacology; Communication; Coronaviridae; Coronavirus Infections - drug therapy; Coronavirus Infections - genetics; Coronavirus OC43, Human - chemistry; Coronavirus OC43, Human - drug effects; Coronavirus OC43, Human - growth & development; Coronaviruses; COVID-19; DNA helicase; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Drug development; Fetuses; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; flavonoids and their derivatives; Hesperidin; Humans; IL-1β; Interleukin 6; Interleukin 8; Interleukins - antagonists & inhibitors; Interleukins - chemistry; Interleukins - genetics; Interleukins - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - virology; Lung - drug effects; Lung - pathology; Lung - virology; Mice; Molecular Docking Simulation; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Pandemics; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; phytomedicine; Phytotherapy - methods; Pneumonia, Viral - drug therapy; Pneumonia, Viral - genetics; Primary Cell Culture; Protein Binding; Protein Interaction Domains and Motifs; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - chemistry; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; SARS-COV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; smart nanoparticles; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Thermodynamics; Tumor necrosis factor-α; Virus Internalization - drug effects; Viruses; COVID-19; flavonoids and their derivatives; smart nanoparticles; phytomedicine; SARS-COV-2
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25112707

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.