Therapeutic Potential of Flavanones against SARSCoV-2

Abstract

The emergence of SARS-CoV-2 in late 2019 and the subsequent COVID-19 pandemic have highlighted an urgent global demand for developing potent antiviral therapies with minimal side effects. Despite advances in current treatments, they remain limited and non-specific medications. Natural phytochemicals, particularly flavanones, a subclass of flavonoids with diverse biological properties, have emerged as promising antiviral candidates. This review explores flavanones’ potential against SARS-CoV-2, focusing on their chemistry, occurrence, mechanism of action, key active compounds, challenges to their application, and structure-activity relationships (SARs). A comprehensive literature review was conducted using multiple electronic databases, including Scopus, PubMed, Google Scholar, and ScienceDirect. Evidence from previous computational, cellular, and animal models underscores flavanones’ multifaceted mechanisms, including direct viral enzyme inhibition and immunomodulation to mitigate cytokine storms. Flavanones such as hesperidin, naringin, and their aglycones exhibit significant potential for combating the COVID-19 pandemic, though challenges such as poor solubility and insufficient clinical data remain. SAR insights showed how structural modifications, specifically glycosylation, could enhance potency and bioavailability. These findings could position flavanones as valuable scaffolds for developing novel anti-COVID-19 agents and optimizing current therapeutic protocols. Further studies are warranted to transform these research insights into clinical applications.