Abstract: Received: 30 May 2020 Revised: 15 June 2020 Accepted: 16 June 2020 DOI: 10.1002/ptr.6793 LETTER TO THE EDITOR Covid-19 and thymoquinone: Connecting the dots At present, the medical approaches to cope with Covid-19 infection systemic inflammation of sepsis including vasodilatation, altered caused by the respiratory syndrome coronavirus 2 (SARS-CoV-2) are vascular permeability and extravasation, leukocyte migration, and mainly supportive. In the absence of specific anti-viral therapies or activation (Ince et al., 2016). Notably, inflammatory cytokines such as vaccines, the medical care is complemented with different combina- TNF-α, IL-1α, IL-2, IL-6, and IL-10 also enhance NO production tions via iNOS (Green et al., 1994). Thymoquinone has been shown to of broad-spectrum antiviral agents, antibiotics, hydro- xychloroquine, and convalescent plasma transfusion (Jin et al., 2020). downregulate inflammatory cytokines, reduce NO levels, and improve Thymoquinone, the main constituent of Nigella sativa, has demon- organ functions and survival of sepsis in an animal model (Alkharfy strated anti-inflammatory, anti-oxidant, anti-tumor, and antimicrobial et al., 2015). This perhaps through a redox mechanism, which activities (Banerjee et al., 2009; Chaieb, Kouidhi, Jrah, Mahdouani, & decreases the systemic oxidative stress and inflammatory response. Bakhrouf, 2011). Thymoquinone was also effective and tolerable in Consequently, thymoquinone decreases the levels of early-stage sep- children with intractable epilepsy in a randomized controlled clinical sis biomarkers (e.g., ESM-1, CRP, and VEGF) by 30–50% (Alkharfy trial at a dose of 1 mg/kg/day orally (Akhondian et al., 2011). Interest- et al., 2018). Interestingly, thymoquinone has also been found to have ingly, thymoquinone and Nigella sativa extract were found to be effec- a protective effect against lung fibrosis and collagen deposition by tive against avian influenza virus (H9N2 AIV) and a murine modulating the nuclear factor Kappa-B (NF-κB) and the antioxidant cytomegalovirus infection model (Salem & Hossain, 2000; Umar enzyme nuclear factor 2 heme oxygenase-1 (Nrf2/HO-1) signaling et al., 2016). Ulasli and co-workers reported that the treatment of pathway (Ahmad et al., 2020). cells with Nigella sativa extract prior to infection with coronavirus Virus-induced phagocyte activation is correlated with oxidative decreases the replication of the virus (Ulasli et al., 2014). Moreover, stress, not just because ROS is produced, but also because activated gene expression analysis of the transient receptor potential proteins phagocytes also produce inflammatory cytokines by the activation of (TRPs) showed a reduction in virus loads upon extract treatments, NF-κB (S. F. Liu & Malik, 2006; Schwarz, 1996). Actually, many genes which can decrease coronavirus survival inside cells. It should be that are regulated by NF-κB, including inflammatory cytokines, noted, however, that these studies on the herbal extracts may not COX-2, and iNOS, contribute to a rise in sepsis inflammatory have been carried out according to the more recent scientific qualita- responses (Ghosh, May, & Kopp, 1998; Schneider-Stock, Fakhoury, tive standards for plant-derived products (Heinrich et al., 2020). Zaki, El-Baba, & Gali-Muhtasib, 2014). Thus, NF-κB inhibition can sup- Therefore, there is the possibility that high concentrations in vitro or press inflammatory genes,..