By the end of 2019, an outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan city in China was detected and spread all over the world 1. On 10th October 2020, the number of confirmed cases of coronavirus disease (COVID-19) reached more than 37 M worldwide with + 1M total death, as reported in the World Health Organization (WHO). The associated pneumonia with the novel viral infection, COVID-19, is divided into three phases that correspond to different clinical stages of the disease 2. Stage 1 is the asymptomatic stage, where the inhaled virus binds to nasal epithelial cells in the nasal cavity and starts replicating. Stage 2 is the upper airway stage, where the virus propagates, migrates down the respiratory tract along the conducting airways, and a more robust innate immune response is triggered. About 20% of the infected patients will progress to stage 3 disease and develop pulmonary infiltrates. Some of these patients will develop a very severe disease as the virus reaches alveoli in the lung and infects alveolar type II cells in peripheral and sub-pleural areas of the lung 3. SARS-CoV-2 propagates within type II cells, large numbers of viral particles are released, and the cells undergo apoptosis and die. Therefore, the spectrum of symptomatic COVID-19 ranges from mild respiratory tract infection to severe pneumonia that may progress to fatal respiratory syndrome and multi-organ malfunctions 2.
Thymol, known as 2-isopropyl-5-methylphenol, is a natural mono-terpenoid phenol derivative of Cymene. It is found in thyme oil and extracted from Thymus vulgaris 4. Thymol is a white crystalline substance that has a pleasant aromatic odor. Thymol also provides the distinctive and robust flavor of the culinary herb thyme.
Carvacrol is known as monoterpenoid phenol and extracted from Oregano. It has a characteristic pungent and warm odor 5.
Hesperidine is a common flavone glycoside found in citrus fruit such as lemons and sweet oranges 6,7. It has several pharmacological activities such as antihyperlipidemic, anti-atherogenic, venotonic, antidiabetic, cardioprotective, anti- antihypertensive, and inflammatory actions 6,7. The anti-inflammatory activity of hesperidin was mainly attributed to its antioxidant defense mechanism and suppression of pro-inflammatory cytokine production 6. Hesperidin exhibited antiviral activity against the influenza virus through a significant reduction of viral replication.
Nigella sativa (NS) contains many active molecules, such as Thymoquinone (TQ), two forms of alkaloids: isoquinoline alkaloid that includes nigellicimine, nigellicimine n-oxide and pyrazol alkaloid that includes nigellidine and nigellicine 8,9. TQ is the most abundant constituent in the volatile oil of Nigella sativa seeds, and most of the herb’s properties are attributed to it 10,11. It has been reported that NS oil can decrease the viral count of HCV in patients received capsules of NS oil (450 mg) three times a day over a 3-month period 12. Moreover, two clinical studies documented to sustained sero-reversion of the HIV virus over treatment period of 6 to 12 months 13–15.
Molecular docking represents a promising in silico method used to predict the binding affinities of small molecules to proteins as a first step in structure based drug design 16–21. This study investigated many active ingredients that showed antiviral activities against SARS-CoV-2, such as Thymol, Carvacrol, Hesperidine, and Thymoquinone. Molecular docking is used to test the binding affinities of these natural product derived compounds against different viral and host cell proteins. Additionally cytotoxicity assay and plaque reduction assay are used to verify their antiviral activity against SARS-CoV-2 collected from Egyptian patients.