Black Cumin Seed (Nigella sativa) against coronavirus disease (COVID-19)
The objective is to assess the potential of black cumin seed (Nigella Sativa) and thymoquinone as its bioactive constituent, to be used against COVID-19 disease, based on the following:
- Efficacy: history of use (previous disease & conditions) for antiviral and immunomodulatory effects of both Nigella sativa seeds and thymoquinone.
- Safety: toxicity studies, side effects and adverse effects if any for both Nigella sativa seeds and thymoquinone.
Electronic databases (PubMed, Google Scholar, Cochrane Clinical Trial Registry) were searched using predetermined terminologies. All clinical and preclinical studies that use Nigella sativa in any antiviral or immune response studies published from 2005 to 2020 were included. Emphasis was placed on studies involving the respiratory system.
Results and discussion:
Antiviral – A total of six studies consisting of two human studies and four animal studies reported on Nigella sativa (Ns) and thymoquinone antiviral effects on different virus species. One interventional human trial reported efficacy of Ns supplementation against hepatitis C virus, while 2 case studies showed improvements in viral load and CD4 counts among sero-positive human immunodeficiency virus (HIV) patients. The animal studies reviewed, experimented on murine cytomegalovirus, and another on Newcastle Disease virus species. However, there was one in-vitro study identified, conducted on a different strain of murine coronavirus (mouse hepatitis virus–A59), reporting Ns extract effects on inhibition of viral replication through alteration of gene expression. Thymoquinone activity was mainly demonstrated preclinically, showing activities against influenza virus strain (H9N2) and the Epstein-Barr virus.
Immunomodulatory, anti-inflammatory- Activities involving the respiratory system have extensively been studied. Several human studies have specified Ns supplementation as being beneficial for improving clinical symptoms and lung function, in cases of obstructive lung diseases and allergic conditions by enhanced immune response and suppression of inflammatory mediators. However, superiority to conventional drugs has not been proven and is seen more as an adjuvant therapy.
Safety: Two human studies showed that Nigella sativa seeds are relatively safe at low doses, with a daily intake of 3g/day of seeds up to 3 months showing no serious adverse effects or organ toxicity. Nevertheless, one study has reported on potential herbal-drug interaction involving metabolism of dextromethorphan (cough suppressant medicine) which may affect other CYP2D6 and CYP3A4 substrates. (e.g. ritonavir, opioids, glucocorticoids) used in supportive treatment of COVID-19.
On the other hand, thymoquinone has shown safety concerns from several animal studies, involving serious adverse effects (death and liver toxicity) at high doses of 2 to 3g/kg, of which safety margin for use in humans has not been established.
Nigella sativa seed extracts have shown potential antiviral and immunomodulatory activities experimentally. However, efficacy is seen among different virus species and strains, which may not resemble the structure or pathogenesis similar to the coronavirus species (SARS-CoV-2) implicated in COVID-19. Current evidence is still insufficient to claim effectiveness against curing the COVID-19 disease specifically but may have a supportive effect in alleviating respiratory symptoms associated with it. As for safety, animal studies reported N. sativa seeds are relatively safe at low doses, but the thymoquinone compound requires further evaluation.