*Communication* **Potential of Flavonoid-Inspired Phytomedicines against COVID-19**

**Wilfred Ngwa 1,2,\*, Rajiv Kumar 3,4, Daryl Thompson 5, William Lyerly 5, Roscoe Moore 5, Terry-Elinor Reid 6, Henry Lowe 7,8 and Ngeh Toyang 7,8**


Academic Editor: H.P. Vasantha Rupasinghe Received: 19 May 2020; Accepted: 5 June 2020; Published: 11 June 2020

**Abstract:** 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.

**Keywords:** flavonoids and their derivatives; phytomedicine; COVID-19; SARS-COV-2; smart nanoparticles
