Can limonene be a possible candidate for evaluation as an agent or adjuvant against infection, immunity, and inflammation in COVID-19?

Coronavirus disease (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite the tremendous social preventive measures. The therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation. The identification of candidate drugs effective for COVID-19 is crucial, thus many natural products including phytochemicals are also being proposed for repurposing and evaluated for their potential in COVID-19. Among numerous phytochemicals, limonene (LMN), a dietary terpene of natural origin has been recently showed to target viral proteins in the in-silico studies. LMN is one of the main compounds identified in many citrus plants, available and accessible in diets and well-studied for its therapeutic benefits. Due to dietary nature, relative safety and efficacy along with favorable physicochemical properties, LMN has been suggested to be a fascinating candidate for further investigation in COVID-19. LMN showed to modulate numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. We hypothesized that given the pathogenesis of COVID-19 involving infection, inflammation, and immunity, LMN may have potential to limit the severity and progression of the disease owing to its immunomodulatory, anti-inflammatory, and antiviral properties. The present article discusses the possibilities of LMN in SARS-CoV-2 infections based on its immunomodulatory, anti-inflammatory, and antiviral properties. Though, the suggestion on the possible use of LMN in COVID-19 remains inconclusive until the in-silico effects confirmed in the experimental studies and further proof of the concept studies. The candidature of LMN in COVID-19 treatment somewhat appear speculative but cannot be overlooked provided favorable physiochemical and druggable properties. The safety and efficacy of LMN are necessary to be established in preclinical and clinical studies before making suggestions for use in humans.