Randomized Double-blind Controlled Parallel Study of (Hesperidin and Diosmin Mixture) for Treatment of COVID-19 Newly Diagnosed Patients in Egypt

Research Background and Rationale At the end of December 2019, pneumonia of unknown origin was detected in the hospitals of Wuhan city, China, and reported to the WHO country office for the first time [1-3]. After a few days, the Chinese government has confirmed the human-to-human transmission of the new infectious respiratory disease [4]. At the end of January 2020, the WHO declared the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV-2), as an international public health emergency. The disease termed coronavirus 19 (COVID-19) rapidly transmitted from China to all over the world and subsequently the WHO declared it a global pandemic disease. The virulent virus structure is closely related to (SARS-CoV) strain with a single-stranded positive-sense RNA composition[5].

This pandemic disease is particularly of major importance to the whole world and especially to countries with a heavy population like Egypt. There is a critical need for emergent, continuous, and cost-effective health care delivery to infected people. Early detection and strategies for prevention of progression of COVID-19 would make a major difference for infected patients and would also be economically beneficial for a resource-constrained country.

People infected with COVID-19 may have no symptoms but still, act as a source of infection to other surrounding persons. The most common clinical manifestations following infection range from mild symptoms of (generalized fatigue, dry cough, low-grade fever, and sore throat) to severe symptoms of (typical severe acute respiratory distress syndrome (ARDS) and pneumonia)[6]. Although the tremendous scientific research effort is focusing mainly on the use of antiviral drugs, certain drug repurposing, and vaccine production for the treatment of COVID-19 patients, there is no specific cure or vaccine for treatment up till now. New drug development is a time-consuming process so that drug repositioning may be the optimum solution to control this pandemic infection.

Selected Drugs Hesperidin is a common flavone glycoside found in citrus fruit such as lemons and sweet oranges[7, 8]. Hesperidin has several pharmacological activities such as anti-atherogenic, antihyperlipidemic, antidiabetic, venotonic, cardioprotective, anti-inflammatory, and antihypertensive actions. The anti-inflammatory activity of hesperidin was mainly attributed to its antioxidant defense mechanism and suppression of pro-inflammatory cytokine production[7]. Hesperidin exhibited anti-viral activity against the influenza virus through a significant reduction of virus replication. Treatment of infected cells with hesperidin enhanced cell-autonomous immunity via activation and upregulation of p38 and JNK expression which is essential for cell defense mechanisms against influenza virus[9].

Hesperidin has been used as an herbal medicine for a long time. 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 2g /kg [10].