Colloidal bismuth and NAC inhibit SARS-CoV-2 replication

This article shows that combining two over-the-counter drugs, colloidal bismuth, and NAC, effectively prevents SARS-CoV-2 replication.[1]

Even though the study used colloidal bismuth, the authors mentioned that other forms of bismuth, like bismuth subsalicylate, will work the same.

Bismuth subsalicylate is the active ingredient in Pepto-Bismol®, while Colloidal Bismuth Salicylate (CBS) is present in De-Nol® and Lizhudele®.

N-Acetylcysteine (NAC) is used for acetaminophen (Tylenol®) or paracetamol poisoning. NAC is sold as a dietary supplement.

Bismuth as antimicrobial

Bismuth is known to have antimicrobial properties against Helicobacter Pylori, which is why it is used as part of the treatment protocol against peptic ulcer disease.

In their previous animal research, the authors have shown that bismuth in the form of colloidal bismuth salicylate combined with ranitidine decreased SARS-CoV-2 viral loads in both upper and lower respiratory tracts.[2]

However, they had to inject the bismuth ranitidine combination inside the abdominal cavity since less than 1% of bismuth is absorbed by oral intake. The problem is that human intraabdominal injections are risky and would be unacceptable to most.

In their study, they used Syrian golden hamsters infected with SARS-CoV-2. These rodents closely resemble the human response to SARS-CoV-2 viruses, the cause of COVID-19.[1]

They demonstrated that when Bismuth was mixed with three or more molar equivalents of NAC, Bi(NAC)₃would form rapidly. The result is increased absorption of bismuth in the gastrointestinal tract.

Bi(NAC)₃, the likely active component of CBS+3NAC, is highly stable and water-soluble.

The higher absorption led to a substantial decrease in SARS-CoV-2 viral loads in the lungs and lessened the pathology in the lungs of the animals. Increased bismuth levels were also seen in the kidneys, spleen, and liver.

Anti-SARS-CoV-2 effects of bismuth

CBS+3NAC interfered with the SARS-CoV-2 entry by inhibiting the activity of angiotensin-converting enzyme 2 (ACE2). The SARS-CoV-2 uses ACE2 receptors to enter human cells.

Previous in vitro studies showed that ranitidine bismuth citrate and its related compounds inhibited several viral enzymes needed for the SARS-CoV-2 replication like the ATPase and helicase.

Effective to other coronaviruses

Bismuth+3NAC had the same inhibiting effects on replication against the SARS-CoV-2 Alpha variant (B.1.1.7), the deadly Middle Eastern Coronavirus (MERS-CoV) and the seasonal human coronavirus 229E in their human cellular models.

The graphs below show the decrease in the SARS-CoV-2, Alpha variant, MERS, and HCoV229E upon exposure to increasing concentrations of CBS+3NAC.

Source: Wang R et al. Orally administered bismuth drug together with N-acetyl cysteine as a broad-spectrum anti-coronavirus cocktail therapy. Chem Sci. 2021

Safety

Importantly, Bismuth is safe for human hosts and toxic only to germs. Hong et al. demonstrated that bismuth triggers a mechanism that involves glutathione that prevents the extra and intracellular accumulation of bismuth and toxicity.

Kidney toxicity is considered the major adverse effect of high-dose intake of bismuth. However, the authors showed minor or reversible renal damage following the intake of CBS (500 mg kg⁻¹) + 3NAC (580 mg kg⁻¹) for four consecutive days.

(Note: I’m not familiar with mg kg^−1.I found in Quora that it is the same as mg/kg. Let me know if you think otherwise.)

Use of Bismuth in humans with COVID-19

Other investigations about using bismuth for COVID-19 in humans are already published. However, they did not combine the bismuth with NAC.

Recently, I wrote about the effectiveness of bismuth among eight patients hospitalized with COVID-19 pneumonia. In that article, the oxygen needed by seven out of eight patients significantly decreased after bismuth subsalicylate use.[4]

Please read about it at Pepto-Bismol for COVID-19.

In another research, many human subjects with COVID-19 cannot tolerate 48 tablets of bismuth subsalicylate in three days. The researchers had to modify the protocol to 24 tablets in three days. There are so many bismuth tablets because less than 1% of bismuth is absorbed by mouth.[3]

Despite the decrease, the results showed that fifty percent of patients who completed the BSS study had negative salivary SARS-CoV-2 after 48 hours of Bismuth subsalicylate.[3]

COVID-19 symptoms also improved. Cough, headache, and fatigue changed the most during bismuth subsalicylate treatment. Seven of 10 patients had their cough resolved. Three out of four cleared their headache, and 2 out of 7 decreased perceived fatigue.[3]

With the findings of the increased absorption and effectiveness of bismuth with NAC against COVID-19, more studies using fewer bismuth tablets are possible.

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References:

Wang R et al. Orally administered bismuth drug together with N-acetyl cysteine as a broad-spectrum anti-coronavirus cocktail therapy. Chem Sci. 2021 Dec 3;13(8):2238-2248. doi: 10.1039/d1sc04515f. PMID: 35310492; PMCID: PMC8864717.
Yuan S et al. Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters. Nat Microbiol. 2020 Nov;5(11):1439-1448. doi: 10.1038/s41564-020-00802-x. Epub 2020 Oct 7. PMID: 33028965.
Yacyshyn MB et al. Feasibility study of Bismuth Subsalicylate (BSS) as an addition to standard of care for COVID-19 therapy. Curr Ther Res Clin Exp. 2022;96:100667. doi: 10.1016/j.curtheres.2022.100667. Epub 2022 Mar 30. PMID: 35370296; PMCID: PMC8964506.
Kahlenborn C, Severs WB and Nawab K (2022) Bismuth subsalicylate as potential treatment for Covid-19 pneumonia: A case series report. Front. Drug. Discov. 2:962988. doi: 10.3389/fddsv.2022.962988

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