Protective role of engineered extracellular vesicles loaded quercetin nanoparticles as anti-viral therapy against SARS-CoV-2 infection: A prospective review

Abstract

Quercetin (QCT) is a naturally occurring phenolic flavonoid compound with inbuilt characteristics of antioxidant, anti-inflammatory, and immune protection. Several recent studies have shown that QCT and QCTits nanoparticles have therapeutic potential against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Novel therapeutics also include the implication of extracellular vesicles (EVs) to protect from SARS-CoV-2 viral infection. This article highlighted the therapeutic/prophylactic potential of engineered EVs loaded with QCT against SARS-CoV-2 infection. Several biotechnological engineering approaches are available to deliver EVs loaded with QCT nanoparticles. Among these biotechnological advances, a specific approach with significantly higher efficiency and yield has to be opted to fabricate such drug delivery of nano molecules, especially to combat SARS-CoV-2 infection. The current treatment regime protects the human body from virus infection but has some limitations including drugs and long-term steroid side effects. However, the vaccine strategy is somehow effective in inhibiting the spread of coronavirus disease-19 (COVID-19) infection. Moreover, the proposed exosomal therapy met the current need to repair the damaged tissue along with inhibition of COVID-19-associated complications at the tissue level. These scientific findings expand the possibilities and predictability of developing a novel and cost-effective therapeutic approach that combines the dual molecule, EVs and QCT nanoparticles, to treat SARS-CoV-2 infection. Therefore, the most suitable engineering method to fabricate such a drug delivery system should be better understood before developing novel therapeutics for clinical purposes.

Quercetin, a Flavonoid with Great Pharmacological Capacity

“…On the other hand, extracellular vesicles (EVs) are nanometer-sized lipid bilayer vesicles secreted by metabolically active cells with the potential for functional and structural modifications for organ-specific drug delivery. Compared to other delivery agents, extracellular vesicles offer several advantages, including biocompatibility; negligible systemic toxicity and adverse effects; enhanced biodistribution; and high transmission efficiency with a tendency to deliver biomolecules, including proteins, peptides, lipids, and nucleic acids [ 144 ]. Previously, extracellular vesicles showed promising potential to provide a wide range of drugs and biomolecules as carriers with significantly enhanced bioavailability and high transmission across the blood–brain barrier (BBB).…”

Effect and mechanism of quercetin or quercetin‐containing formulas against COVID‐19: From bench to bedside

“…These methods include nasal or throat sprays (G. Williamson & Kerimi, 2020), which can achieve a high local concentration of flavanol and prevent viral entry. Other formulation strategies, include using nanosized molecules (Raghav et al, 2022), combining quercetin with metals or vitamins (Shohan et al, 2022), making enzymatic structural modifications (Shohan et al, 2022) The low bioavailability of quercetin results in a substantial portion of the bioactive compound remaining in the intestine. This can considerably affect the gut microbiota and may indirectly influence host immunity, making quercetin potentially beneficial against COVID-19.…”

“…These methods include nasal or throat sprays (G. Williamson & Kerimi, 2020), which can achieve a high local concentration of flavanol and prevent viral entry. Other formulation strategies, include using nanosized molecules (Raghav et al, 2022), combining quercetin with metals or vitamins (Shohan et al, 2022), making enzymatic structural modifications (Shohan et al, 2022), and developing more efficient phospholipid‐based delivery system (Di Pierro et al, 2021), have been suggested as means of improving the bioavailability and effectiveness of quercetin in humans. However, their effects against COVID‐19 remain unproven.…”

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

“…Meanwhile, modified extracellular vesicles (EVs) loaded with nanobodies against the spike protein of SARS-CoV-2 and interferon-beta, a cytokine with antiviral effects, have been reported [61][62][63][64]. EVs are biological substances with a heterogenous lipid bilayer structure that are secreted from almost all living cells and broadly classified into three types: exosomes, microvesicles, and apoptotic bodies, depending on the intracellular production mechanism [65][66][67].…”