Hesperidin; Clinical Trial Candidate For ‘Genius Virus’
Is hesperidin essential for prophylaxis and treatment of COVID-19 Infection?
Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID-19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.
COVID-19 binds to the ACE-2 receptor through its specific Spike-receptor binding domain (RBD) sequence to form the SARS-CoV-2-RBD-ACE-2 complex. The proposed computational activity of 78 anti-viral drugs against the human ACE2 receptor was screened using homology modeling. This study showed that hesperidin is the only compound that could target the binding interface between SARS-CoV-2 Spike and ACE2 human receptors. Based on virtual screening, hesperidin may disrupt the interaction of ACE2 with RBD of SARS-CoV-2 thus block its entry into the lung cells. Therefore, hesperidin can be used as a promising prophylactic agent against COVID-19 infection.
The safety of hesperidin was confirmed by FASEB (Federation of American Societies of Experimental Biology) upon request of the FDA. Toxicity studies have confirmed the high safety profile of hesperidin after oral intake. Results from oral toxicity studies showed the absence of adverse side effects after oral hesperidin ingestion of more than 2 g /kg.
Daflon 500 mg is a marketed tablet dosage form containing a micronized flavonoid mixture of 50 mg of hesperidin and 450 mg of diosmin which used as vasoprotective venotonic agent. This hesperidin mixture is characterized by its high safety profile. Continues oral administration for hesperidin mixture to rats for 13 and 26 weeks, using a very high dose of 35-fold of the daily dosage showed no toxicity with a high LD50 value of more than 3 g/kg body weight. Clinical trials used more than 2850 patients treated with the hesperidin mixture for a period of 6 weeks to 1 year showed normal hematological parameters, hepatic and renal functions with no signs of toxicity.
Hesperidin is a promising drug candidate for the prevention and treatment of COVID-19. To sum it up, hesperidin interferes with viral entry through ACE2 receptors, improves the host cellular immunity, minimizes the release of inflammatory mediators and its mixture protects against venous thromboembolism. We are planning to register a clinal trail on ClinicalTrials.gov to evaluate the clinical efficacy of hesperidin against COVID-19.