Abstract: Received: 15 June 2021 | Revised: 13 July 2021 | Accepted: 14 July 2021 DOI: 10.1111/1440-1681.13553 REVIEW ARTICLE The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases Kaneez Fatima Shad1,2,3,4 | Wissam Soubra1,5,6 | Dennis John Cordato5,7,8 1 University of Technology Sydney, Sydney, Australia 2 Australian Catholic University, Sydney, Australia 3 University of Health Sciences 4 ISRA University Nigella sativa (N. sativa) is an annual flowering plant that has been used as a traditional remedy for many centuries. The seed possesses a large variety of compounds with thymoquinone (TQ) considered its major but not sole bioactive constituent. 5 Ingham Institute for Applied Medical Research 6 Abstract A Health Step Clinic, Sydney, Australia 7 Department of Neurophysiology, Liverpool Hospital, Liverpool, Australia 8 South Western Sydney Clinical School, University of New South Wales, Sydney, Australia Correspondence Kaneez Fatima Shad, School of Life Sciences, University of Technology Sydney, Sydney, Australia. Email: ftmshad@gmail.com, Kaneez. Fatimashad@uts.edu.au Supercritical fluid extraction, geographical location, and oxidative status of N. sativa produces the highest yield of essential oil content including TQ. Thymoquinone is lipophilic, heat and light sensitive with low oral bioavailability and rapid elimination that have significantly inhibited its pharmacological development. Novel developments in nanoparticulate-­based oral administration, nasal spray and transdermal delivery may allow the clinical development of N. sativa and TQ as therapeutic agents. Animal and human studies indicate a potential role of N. sativa seed oil and TQ for a diverse range of disease processes including hypertension, dyslipidaemia, type 2 diabetes mellitus, arthritis, asthma, bacterial and viral infections, neurological and dermatological disorders, as it belongs to the group of pan-­assay interference compounds. This review outlines the pharmacological properties of N. sativa and TQ and their potential wide application for a large variety of human diseases. The paper will focus on recent studies of the anti-­inflammatory and antiviral properties that make N. sativa and TQ promising therapeutic agents targeting contemporary inflammatory and infectious diseases including Covid 19. KEYWORDS Covid 19, oxidative stress, pan-­assay interference compound, SARS-­CoV-­2, supercritical fluid extraction, thymoquinone 1 | been referenced in the Old Testament's Book of Isaiah4 and by the I NTRO D U C TI O N Prophet Muhammad who stated that the black seed is a cure for every disease except death.5 Nigella sativa (N. sativa or black cumin) is an annual flowering plant Nigella sativa seed possesses a large variety of ingredients includ- belonging to the Ranunculaceae (buttercup) family.1-­3 The plant is ing fixed oil, essential or volatile oil, proteins, alkaloids and sapo- native to the eastern Mediterranean, Northern Africa, the Indian nins.1 Oil content of the seed ranges from 30–­4 0%, of which >98% is 1,3 The plant grows 20–­30 cm long, fixed and 0.1–­2% is essential oil.3,6 The major oil components include with a flower containing 5–­10 petals and a fruit comprising a cap- species of triacylglycerol, saturated and unsaturated fatty acids sule of 3–­7 follicles that contain black-­coloured seeds.1 These seeds which may vary according to the extraction method..