Nigella Sativa for COVID-19: real-time analysis of all 19 studies

Nigella Sativa for COVID-19: real-time meta analysis of 7 studies

Covid Analysis (Preprint) (meta analysis)

• Statistically significant improvements are seen for mortality, hospitalization, recovery, cases, and viral clearance. 5 studies from 4 independent teams in 4 different countries show statistically significant improvements in isolation (3 for the most serious outcome).

• Meta analysis using the most serious outcome reported shows 61% [40‑75%] improvement. Results are better for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies. Early treatment is more effective than late treatment.

• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 29% of nigella sativa studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments may be more effective.

• No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.

• All data to reproduce this paper and sources are in the appendix.

Covid Analysis et al., 6/22/2022, preprint, 1 author.

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2

Bencheqroun et al., Pathogens, doi:10.3390/pathogens11050551

52 patient RCT in the USA with nigella sativa component thymoquinone, showing improved recovery with treatment. There was a significantly faster decline in the total symptom burden, and a significant increase in CD8+ and helper CD4+ central memory T lymphocytes. The treatment group contained 5 more vaccinated patients and 7 more overweight patients. Authors also present in vitro results showing an inhibitory effect with five SARS-CoV-2 variants including omicron.

risk of hospitalization, 69.3% lower, RR 0.31, p = 0.44, treatment 0 of 29 (0.0%), control 1 of 23 (4.3%), NNT 23, relative risk is not 0 because of continuity correction due to zero events.

time to sustained clinical response, 9.1% lower, HR 0.91, p = 0.78, treatment 28, control 23, Kaplan–Meier.

time to sustained clinical response, 35.5% lower, HR 0.65, p = 0.25, treatment 28, control 23, Kaplan–Meier, high-risk patients.

risk of no viral clearance, 43.5% lower, RR 0.57, p = 0.31, treatment 5 of 21 (23.8%), control 8 of 19 (42.1%), NNT 5.5, day 14.

Bencheqroun et al., 5/7/2022, Double Blind Randomized Controlled Trial, placebo-controlled, USA, North America, peer-reviewed, mean age 45.0, 25 authors, study period 27 May, 2021 - 27 September, 2021.

A phase I clinical trial to evaluate the safety of thymoquinone -rich black cumin oil (BlaQmax®) on healthy subjects: Randomized, double-blinded, placebo-controlled prospective study

Thomas et al., Toxicology Reports, doi:10.1016/j.toxrep.2022.04.020 (Dosing)

Phase 1 trial of high thymoquinone content (5%) black cumin oil finding treatment to be safe without any major side effects or adverse events.

There was a significant reduction in total cholesterol, LDL, and triglycerides, and increased HDL.

Thomas et al., 4/20/2022, Double Blind Randomized Controlled Trial, placebo-controlled, peer-reviewed, 6 authors.

Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection

Shehab et al., Tropical Journal of Pharmaceutical Research, doi:10.4314/tjpr.v21i2.13

Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with nigella sativa prophylaxis in unadjusted analysis. REC/UG/2020/03.

risk of severe case, 0.2% lower, RR 1.00, p = 1.00, treatment 4 of 39 (10.3%), control 22 of 214 (10.3%), NNT 4173, unadjusted, severe vs. mild cases.

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Shehab et al., 2/28/2022, retrospective, multiple countries, multiple regions, peer-reviewed, survey, 7 authors, study period September 2020 - March 2021.

Inhibitory effect of thymoquinone from Nigella sativa against SARS-CoV-2 main protease. An in-silico study

Khan et al., Brazilian Journal of Biology, doi:10.1590/1519-6984.25066

In Silico analysis of thymoquinone from nigella sativa showing good binding affinity with SARS-CoV-2 M^pro.

Khan et al., 1/24/2022, peer-reviewed, 7 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

In vitro Potential Antiviral SARS-CoV-19- Activity of Natural Product Thymohydroquinone and Dithymoquinone from Nigela sativia

Esharkawy et al., Bioorganic Chemistry, doi:10.1016/j.bioorg.2021.105587 (In Vitro)

In Vitro and In Silico study of nigella sativa components, showing anti-SARS-CoV-2 activity at non-cytotoxic nanomolar concentrations for thymohydroquinone with selectivity index 1.4.

Esharkawy et al., 1/1/2022, peer-reviewed, 3 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Nigellidine (Nigella sativa, black-cumin seed) docking to SARS CoV-2 nsp3 and host inflammatory proteins may inhibit viral replication/transcription

Banerjee et al., Natural Product Research, doi:10.1080/14786419.2021.2018430

In Silico study showing nigella sativa docking to SARS CoV-2 Nsp3 and host inflammatory proteins, which may inhibit viral replication.

Banerjee et al., 12/22/2021, peer-reviewed, 6 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis

Rizvi et al., Processes, doi:10.3390/pr9101814

In Silico study predicting that nigella sativa component dithymoquinone has good affinity and stability against SARS-CoV-2 3CL^pro and NSP15, suggesting potential benefits for COVID-19 treatment.

Rizvi et al., 10/13/2021, peer-reviewed, 10 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Efficacy of Persian medicine herbal formulations (capsules and decoction) compared to standard care in patients with COVID-19, a multicenter open-labeled, randomized, controlled clinical trial

Karimi et al., Phytotherapy Research, doi:10.1002/ptr.7277

RCT 358 hospitalized patients in Iran, 184 receiving treatment with a combination of nigella sativa and several other herbal medicines, showing shorter hospitalization time and improved recovery with treatment. IR.TUMS.VCR.REC.1399.024.

risk of death, 50.8% lower, RR 0.49, p = 0.45, treatment 2 of 192 (1.0%), control 4 of 189 (2.1%), NNT 93.

risk of ICU admission, 60.6% lower, RR 0.39, p = 0.28, treatment 2 of 192 (1.0%), control 5 of 189 (2.6%), NNT 62.

hospitalization time, 70.0% lower, HR 0.30, p < 0.001, treatment 184, control 174, Cox proportional hazards, primary outcome.

fever, 66.5% lower, OR 0.33, p = 0.001, treatment 184, control 174, RR approximated with OR.

dyspnea, 13.7% lower, OR 0.86, p < 0.001, treatment 184, control 174, RR approximated with OR.

Karimi et al., 10/4/2021, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 37 authors, study period March 2020 - July 2020, this trial uses multiple treatments in the treatment arm (combined with several herbal medicines) - results of individual treatments may vary.

Identification of SARS-CoV-2 RNA-dependent RNA polymerase inhibitors from the major phytochemicals of Nigella sativa: An in silico approach

Mir et al., Saudi Journal of Biological Sciences, doi:10.1016/j.sjbs.2021.09.002

In Silico study identifying phytochemicals from nigella sativa (𝛼-hederin, dithymoquinone, negillicine, and negillidine) as potential SARS-CoV-2 RNA-dependent RNA polymerase inhibitors.

Mir et al., 9/8/2021, peer-reviewed, 11 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial

Koshak et al., Complementary Therapies in Medicine, doi:10.1016/j.ctim.2021.102769

RCT 183 mild COVID-19 outpatients in Saudi Arabia, 91 treated with Nigella Sativa, showing lower hospitalization and faster recovery with treatment. 500mg Nigella Sativa oil (MARNYS Cuminmar) twice daily for 10 days. NCT04401202.

risk of hospitalization, 74.7% lower, RR 0.25, p = 0.37, treatment 1 of 91 (1.1%), control 4 of 92 (4.3%), NNT 31.

risk of no recovery, 42.7% lower, RR 0.57, p < 0.001, treatment 34 of 91 (37.4%), control 60 of 92 (65.2%), NNT 3.6.

Koshak et al., 8/15/2021, Randomized Controlled Trial, Saudi Arabia, Middle East, peer-reviewed, 10 authors, trial NCT04401202.

Therapeutic Potential of Thymoquinone and Its Nanoformulations in Pulmonary Injury: A Comprehensive Review

Al-Gabri et al., International Journal of Nanomedicine, doi:https://doi.org/10.2147/IJN.S314321 (Review)

Review of thymoquinone (a component of nigella sativa) research, antioxidant, anti-inflammatory, and antineoplastic properties, application to lung conditions, and the potential advantages of nanoformulations on drug solubility, cellular absorption, and drug delivery to lung tissue target sites.

Al-Gabri et al., 7/27/2021, peer-reviewed, 11 authors.

The potential role of thymoquinone in preventing the cardiovascular complications of COVID-19

Ahmad et al., Vascular Pharmacology, doi:10.1016/j.vph.2021.106899 (Review)

Review of the potential role of thymoquinone (a component of nigella sativa) in minimizing cardiovascular complications of COVID-19.

Ahmad et al., 7/23/2021, peer-reviewed, 3 authors.

The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases

Shad et al., Clinical and Experimental Pharmacology and Physiology, doi:10.1111/1440-1681.13553 (Review)

Review of the pharmacological properties of nigella sativa and thymoquinone and application for a variety of diseases, focusing on recent studies of the anti-inflammatory and antiviral properties that are promising for diseases including COVID-19.

Shad et al., 7/23/2021, peer-reviewed, 3 authors.

Exploring the Potency of Nigella sativa Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations

Hardianto et al., Indonesian Journal of Chemistry, doi:10.22146/ijc.65951

In Silico study showing nigella sativa metabolites binding to SARS-CoV-2 M^pro.

Hardianto et al., 7/12/2021, peer-reviewed, 5 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Active-site Molecular docking of Nigellidine to nucleocapsid/Nsp2/Nsp3/MPro of COVID-19 and to human IL1R and TNFR1/2 may stop viral-growth/cytokine-flood, and the drug source Nigella sativa (black cumin) seeds show potent antioxidant role in experimental rats

Maiti et al., Research Square, doi:10.21203/rs.3.rs-26464/v1 (Preprint)

In Silico and animal study of nigella sativa and component nigellidine, showing nigellidine binding activity for several important SARS-CoV-2 proteins and for relevant host receptors; and that black cumin seed extract was antioxidative, hepato- and reno-protective in rats.

Maiti et al., 5/5/2021, preprint, 5 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

In silico identification of compounds from Nigella sativa seed oil as potential inhibitors of SARS-CoV-2 targets

Duru et al., Bulletin of the National Research Centre, doi:10.1186/s42269-021-00517-x

In Silico study of compounds from Nigella Sativa oil. Authors identify component phytochemicals with gas chromatography-mass spectrometry and analyze binding affinity with SARS-CoV-2 targets. Caryophyllene oxide, α-bergamotene, and β-bisabolene were identified as promising candidates for inhibition.

Duru et al., 3/12/2021, peer-reviewed, 3 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Response to Nigella sativa in Patients with Confirmed and Suspected COVID-19

Fetian et al., Healthbook Times, doi:10.36000/hbT.2021.01.001

Retrospective 35 patients treated with Nigella Sativa showing good outcomes and relatively fast recovery. There was no control group.

Fetian et al., 3/4/2021, peer-reviewed, 4 authors.

Preventive Value of Black Seed in People at Risk of Infection with COVID-19

Al-Haidari et al., Pakistan Journal of Medical and Health Sciences, 15:1

Prophylaxis study with 376 mostly high-risk patients, 188 treated with nigella sativa, showing significantly lower cases with treatment. Black seeds 40mg/kg orally once daily.

risk of symptomatic case, 62.2% lower, RR 0.38, p < 0.001, treatment 68 of 188 (36.2%), control 180 of 188 (95.7%), NNT 1.7.

Al-Haidari et al., 1/31/2021, prospective, Iraq, Middle East, peer-reviewed, 3 authors.

Clinical Trial of Black Seeds Against COVID – 19 in Kirkuk City / Iraq

Al-Haidari et al., Indian Journal of Forensic Medicine & Toxicology, 15:3 (preprint 1/2021)

Open-label RCT with 419 patients in Iraq, 160 treated with Nigella Sativa, showing lower mortality and severe cases with treatment. Black seeds 40mg/kg orally once daily for 14 days.

risk of death, 95.8% lower, RR 0.04, p = 0.001, treatment 0 of 160 (0.0%), control 14 of 259 (5.4%), NNT 18, relative risk is not 0 because of continuity correction due to zero events.

risk of severe case, 92.6% lower, RR 0.07, p < 0.001, treatment 2 of 160 (1.2%), control 44 of 259 (17.0%), NNT 6.4.

Al-Haidari et al., 1/31/2021, Randomized Controlled Trial, Iraq, Middle East, peer-reviewed, 3 authors.

Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multi-center placebo-controlled randomized clinical trial

Ashraf et al., medRxiv, doi:10.1101/2020.10.30.20217364 (Preprint)

RCT with 157 patients treated with honey and nigella sativa, and 156 control patients, showing significantly faster recovery and viral clearance. NCT04347382.

Honey (1gm/kg/day) plus encapsulated Nigella sativa seeds (80mg/kg/day) orally in 2-3 divided doses daily for up to 13 days.

risk of death, 81.9% lower, RR 0.18, p = 0.01, treatment 2 of 157 (1.3%), control 11 of 156 (7.1%), NNT 17, all cases.

risk of death, 67.1% lower, RR 0.33, p = 0.49, treatment 0 of 107 (0.0%), control 1 of 103 (1.0%), NNT 103, relative risk is not 0 because of continuity correction due to zero events, moderate cases.

risk of death, 78.8% lower, RR 0.21, p = 0.03, treatment 2 of 50 (4.0%), control 10 of 53 (18.9%), NNT 6.7, severe cases.

risk of no recovery, 83.6% lower, HR 0.16, p < 0.001, treatment 107, control 103, moderate cases.

risk of no recovery, 75.2% lower, HR 0.25, p < 0.001, treatment 50, control 53, severe cases.

risk of no viral clearance, 81.9% lower, HR 0.18, p < 0.001, treatment 107, control 103, moderate cases.

risk of no viral clearance, 76.9% lower, HR 0.23, p < 0.001, treatment 50, control 53, severe cases.

Ashraf et al., 11/3/2020, Randomized Controlled Trial, Pakistan, South Asia, preprint, 48 authors, this trial uses multiple treatments in the treatment arm (combined with honey) - results of individual treatments may vary, trial NCT04347382.

Promising preventive and therapeutic effects of TaibUVID nutritional supplements for COVID-19 pandemic: towards better public prophylaxis and treatment (A retrospective study)

El Sayed et al., Am J Blood Res., doi:

Small retrospective study of 20 patients in Egypt suggesting benefits of TaibUVID (nigella sativa, chamomile and honey) treatment.

El Sayed et al., 10/15/2020, Egypt, Africa, peer-reviewed, 18 authors, this trial uses multiple treatments in the treatment arm (combined with chamomile and honey) - results of individual treatments may vary.

Potential influence of Nagella sativa (Black cumin) in reinforcing immune system: A hope to decelerate the COVID-19 pandemic

Kulyar et al., Phytomedicine, doi:10.1016/j.phymed.2020.153277 (Review)

Review of immune-regulating, anti-inflammatory, and antioxidant benefits of nigella sativa, and potential benefits for COVID-19.

Kulyar et al., 7/10/2020, peer-reviewed, 6 authors.

Covid-19 and thymoquinone: Connecting the dots

Ahmad et al., Phytotherapy Research, doi:10.1002/ptr.6793 (Review) (Preprint)

Review of the potential benefits of thymoquinone (a component of nigella sativa) for COVID-19, recommending clinical trials.

Ahmad et al., 6/26/2020, preprint, 4 authors.

Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study

Bouchentouf et al., ChemRxiv, doi:10.26434/chemrxiv.12055716.v1 (Preprint)

In Silico study of compounds from nigella sativa identifying nigellidine and α-Hederin as potential compounds that inhibit SARS-CoV-2.

Bouchentouf et al., 4/2/2020, preprint, 2 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Antiandrogens	(meta)	Lactoferrin	(meta)
Aspirin	(meta)	Melatonin	(meta)
Bamlaniv../e..	(meta)	Metformin	(meta)
Bebtelovimab	(meta)	Molnupiravir	(meta)
Bromhexine	(meta)	N-acetylcys..	(meta)
Budesonide	(meta)	Nigella Sativa	(meta)
Cannabidiol	(meta)	Nitazoxanide	(meta)
Casirivimab/i..	(meta)	Paxlovid	(meta)
Colchicine	(meta)	Peg.. Lambda	(meta)
Conv. Plasma	(meta)	Povidone-Iod..	(meta)
Curcumin	(meta)	Probiotics	(meta)
Diet	(meta)	Proxalutamide	(meta)
Ensitrelvir	(meta)	Quercetin	(meta)
Ensovibep	(meta)	Remdesivir	(meta)
Exercise	(meta)	Sleep	(meta)
Famotidine	(meta)	Sotrovimab	(meta)
Favipiravir	(meta)	Tixagev../c..	(meta)
Fluvoxamine	(meta)	Vitamin A	(meta)
Hydroxychlor..	(meta)	Vitamin C	(meta)
Iota-carragee..	(meta)	Vitamin D	(meta)
Ivermectin	(meta)	Zinc	(meta)

Other Treatments		Global Adoption