Back to the nature: thymoquinone as an enemy against Covid-19 life cycle

Back to the nature: thymoquinone as an enemy against Covid-19 life cycle
Sanaz Raeisi,^1,* Amirhossein Kheirkhah,²
1. Master of Medical Biotechnology, Department of Genetics, Shahid Sadoughi University of Medical Science, Yazd
2. Master of Medical Biotechnology, Department of Genetics, Shahid Sadoughi University of Medical Science, Yazd
Introduction: Nature is a great source of medicinal drugs or their precursors. many approved drugs are based on natural products. most of the time, natural products able to cross the biological barriers and penetrate cells, which enables them to be ignition points for the leads in drug discovery with desirable pharmacokinetic properties. Thymoquinone is a bioactive compound isolated from Nigella sativa. according to numerous pharmacological studies, thymoquinone has been found to be a very promising natural product. the components of this plant are known for its intense immune-regulatory, anti-inflammatory, and antioxidant benefits in obstructive respiratory disorders. a molecular docking study also gave evidence that thymoquinone decelerates COVID-19 and might give the same or better results than the FDA approved drugs. The aim of this review was to investigate the possible immune-regulatory effects of thymoquinone on the COVID-19 pandemic.
Methods: COVID-19 is a member of Beta coronaviruses like the Severe Acute Respiratory Syndrome Human coronavirus (SARS HCoV) and the Middle-East Respiratory Syndrome Human coronavirus (MERS HCoV). in the absence of specific antiviral therapies or vaccines, medical care is complemented with different combinations of broad‐spectrum antiviral agents, antibiotics, hydroxychloroquine, and convalescent plasma transfusion. Thymoquinone, the main constituent of Nigella sativa, has demonstrated anti‐inflammatory, anti‐oxidant, anti‐tumoral, and antimicrobial activities. recently, molecular docking studies have shown that thymoquinone may inhibit SARS‐CoV‐2 and interfere with its binding to ACE2 receptors. this can avert virus entry and replication inside the host cell. Furthermore, SARS‐CoV‐2 spikes can bind to a cell surface heat shock protein (HSPA5), which is upregulated during viral infections. molecular dynamics simulations showed that thymoquinone can interfere with the attachment of SARS‐CoV‐2 to the HSPA5 substrate‐binding domain b (SBDb) on the stressed cells, and consequently may reduce the risk of infection. interestingly, thymoquinone was found to be effective against the avian influenza virus (H9N2 AIV) and a murine cytomegalovirus infection model. Thymoquinone has been shown to downregulate inflammatory cytokines, reduce NO levels, and improve organ functions and survival of sepsis in an animal model.
Results: Thymoquinone as a compound has revealed a remarkable immunomodulatory activity at specific doses. This perhaps through a redox mechanism, which decreases the systemic oxidative stress and inflammatory response. interestingly, thymoquinone has also been found to have a protecting effect against lung fibrosis and collagen deposition by modulating the nuclear factor Kappa‐B (NF‐κB) and the antioxidant enzyme nuclear factor 2 heme oxygenase‐1 (Nrf2/HO‐1) signaling pathway. virus‐induced phagocyte activation is correlated with oxidative stress, not just because ROS is produced, but also because activated phagocytes also produce inflammatory cytokines by the activation of NF‐κB. Actually, many genes are regulated by NF‐κB, including inflammatory cytokines, COX‐2, and iNOS. thus, NF‐κB inhibition can suppress inflammatory genes, impede the cytokine storm, and reduce immune cells infiltration and activation, and, therefore, protecting against tissue and organ damage.
Conclusion: No effective therapy is yet available for the new species of Coronavirus, SARS-Cov-2. Thymoquinone is a natural plant product with high safety and low toxicity such that people take it as a diet supplement, and growing evidence from preclinical studies demonstrates that it effectively inhibits viral infection, alleviates the severity of lung injury through offsetting the cytokine storm, inhibits subsequent fibrosis, and increases survival rates, therefore, the time is probably appropriate to move thymoquinone from experimentation on the bench to clinical testing for the Covid‐19 pandemic.
Keywords: : Thymoquinone, immunomodulatory response, Covid-19