CELLULAR Health and 

Questions and Answers

Dr. Aleksandra Niedzwiecki PhD, Dr. Matthias Rath, MD

Dr. Rath Research Institute relevant publications:

Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants.

Despite vaccine availability, the global spread of COVID-19 continues, largely facilitated by emerging SARS-CoV-2 mutations. Our earlier research documented that a specific combination of plant-derived compounds can inhibit SARS-CoV-2 binding to its ACE2 receptor and controlling key cellular mechanisms of viral infectivity. In this study, we evaluated the efficacy of a defined mixture of plant extracts and micronutrients against original SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants. The composition containing vitamin C, N-acetylcysteine, resveratrol, theaflavin, curcumin, quercetin, naringenin, baicalin, and broccoli extract demonstrated a highest efficacy by inhibiting the receptor-binding domain (RBD) binding of SARS-CoV-2 to its cellular ACE2 receptor by 90%. In vitro exposure of test pseudo-typed variants to this formula for 1 h before or simultaneously administrated to human pulmonary cells resulted in up to 60% inhibition in their cellular entry. Additionally, this composition significantly inhibited other cellular mechanisms of viral infectivity, including the activity of viral RdRp, furin, and cathepsin L. These findings demonstrate the efficacy of natural compounds against SARS-CoV-2 including its mutated forms through pleiotropic mechanisms. Our results imply that simultaneous inhibition of multiple mechanisms of viral infection of host cells could be an effective strategy to prevent SARS-CoV-2 infection.

Goc A, Niedzwiecki A, Ivanov V, Ivanova S, Rath M. Eur J Microbiol Immunol (Bp). 2022;11(4):87-94.
Available at: https://akjournals.com/view/journals/1886/11/4/article-p87.xml

Simultaneous Inhibition of SARS-CoV-2 Infectivity by a Specific Combination of Plant-derived Compounds.

SARS-CoV-2 pandemic remains a challenge to human health and economy worldwide. Previously we have shown that a combination of active plant-derived compounds and plant extracts can dose-dependently inhibit binding of RBD-spike protein SARS-CoV-2 to the ACE2 receptor and its expression on human alveolar epithelial cells. Here we use eGFP-luciferase-SARS-CoV-2 spike protein pseudo-virions and SARS-CoV-2-RdRp, to show if the antiviral effectiveness of this combination of plant-derived compounds and plant extracts expands to other important key mechanisms of SARS-CoV-2 infection. Or results revealed that this combination of five plant-derived compounds inhibited the attachment of the SARS-CoV-2 pseudo-typed particles with lung hACE2/A549 cells. In addition, it down-regulated the activity of key enzymes known to be crucial for the entry of the SARS-CoV-2 virus, such as TMPRSS2, furin and cathepsin L, but not their expression at protein level. This combination did not affect ACE2 binding to and ACE2 enzymatic activity, but modestly decrease cellular expression of neuropilin-1 molecule and significantly inhibited activity of viral RdRp. This study demonstrates inhibitory effects of this combination on key cellular mechanisms of SARS-CoV-2 infection. The findings further support the use of plant-derived compounds as effective health measures against SARS-CoV-2-caused infection.

Goc A, Ivanov V, Ivanova S, Chatterjee M, Rath M, Niedzwiecki A. Eur J Bio Biotech 2021;2(5)
Available at: https://ejbio.org/index.php/ejbio/article/view/258

Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions.

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3’-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3’-digallate at 25 μg/ml and curcumin above 10 μg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3’-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3’-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.

Goc A, Sumera W, Rath M, Niedzwiecki A.PLOS ONE 2021;16(6):e0253489
Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253489

Inhibition of ACE2 expression by Ascorbic acid alone and its combination with other natural compounds.

Our study provides valuable experimental confirmation of the efficacy of micronutrients in controlling ACE2 expression—the coronavirus cellular “entry” point. It further validates the importance of nutrient interactions in various aspects of cellular metabolism and in considering potential therapeutic applications of nutrient-based approaches. The study shows that ascorbic acid and its combination with some natural compounds could be included in developing preventive and therapeutic approaches toward the current pandemic.

Ivanov V, Goc A, Ivanova S, Niedzwiecki A, Rath M. Infect Dis (Auckl) 2021;14:1178633721994605.
Available at: https://journals.sagepub.com/doi/10.1177/1178633721994605

Scientific basis of micronutrient applications as an effective, safe, and affordable global public health strategy to help control the coronavirus pandemic.

These and other findings confirm the significant potential of micronutrients, especially when applied in a specific combination, as a new therapeutic strategy in controlling the COVID-19 pandemic. This direction shows superiority to other currently applied measures by simultaneously affecting key infection mechanisms used by SARS-CoV-2 and other coronaviruses: viral entry, its replication potential, and the expression of cellular ACE2 receptors. In addition, the general safety of natural compounds makes this approach a safe and effective alternative that can be used by the general public. Health practitioners in particular should consider micronutrient deficiencies as a key factor when evaluating patients with COVID-19 conditions. Since screening for these deficiencies can be difficult or impractical, it is prudent to assume nutrient compromising status in all patients and to apply targeted micronutrient supplementation as a general strategy to COVID-19.

Niedzwiecki A, Rath M. J Cellular Medicine and Natural Health 2021, January.
Available at: https://jcmnh.org/index.php/2021/01/19/scientific-basis-of-micronutrient-applications-as-an-effective-safe-and-affordable-global-public-health-strategy-to-help-control-the-coronavirus-pandemic

The micronutrient combination with immune-enhancing effects.

Infectious diseases have become a growing health problem worldwide. Thus, the search for novel non-toxic and effective approaches with immune system- enhancing effects, so it can resist and fight these infections is still sought after. It has been firmly established that both nutrition and the availability of specific micronutrients are important for achieving optimum immunity. In this study, we investigated the effects of natural compounds in enhancing the cellular response of immune cells to various challenges. The results showed that some vitamins, minerals, and plant extracts had significant enhancing effects on specific immune responses tested in this study. However, a combination of these natural compounds had superior efficacy compared to any of the individual substances in increasing phagocytic activity against specific bacteria and yeast. This micronutrient combination also increased the efficacy of NK cells in eliminating abnormal (cancer) cells as well as inhibiting the release of pro- inflammatory IL-6 by RAW macrophages. This composition of nutrients offers significant pleiotropic benefits in supporting the immune system function.

Sumera W, Goc A, Niedzwiecki A, Rath M. J
Cellular Medicine and Natural Health 2020, August
Available at: https://jcmnh.org/index.php/2020/08/28/the-micronutrient-combination-with-immune-enhancing-effects

Micronutrient combination inhibits two key steps of coronavirus (SARS-CoV-2) infection: viral binding to ACE2 receptor and its cellular expression.

This study provides the basis for an effective and safe public health strategy based on optimum intake of micronutrients. It allows people around the world to actively participate in the prevention of coronavirus infections – beyond wearing masks, social distancing and other defensive measures.

Goc A, Sumera W, Ivanov V, Niedzwiecki A, Rath M. J Cellular Medicine and Natural Health 2020, August
Available at: https://jcmnh.org/index.php/2020/08/14/micronutrient-combination-inhibits-two-key-steps-of-coronavirus-sars-cov-2-infection-viral-binding-to-ace2-receptor-and-its-cellular-expression/

Effective and safe global public health strategy to fight the COVID-19 pandemic: Specific micronutrient composition inhibits Coronavirus cell-entry receptor (ACE2) expression.

Optimum micronutrient intake is the only scientifically proven way to improve general immune resistance against infections, a fact documented in every leading textbook of biology. This study provides scientific evidence that, in addition, specific micronutrient compositions are powerful tools in the fight against the COVID-19 pandemic.

Both, SARS-CoV-2 – the virus that causes the current pandemic – and other coronaviruses enter body cells via a specific receptor, the Angiotensin-Converting-Enzyme 2 (ACE2). The ACE2 receptor is expressed by many cell types, including lung epithelial cells as well as endothelial cells of the vascular system.

Ivanov V, Ivanova S, Niedzwiecki A, Rath M. J Cellular Medicine and Natural Health 2020, July
Available at: https://jcmnh.org/index.php/2020/07/02/effective-and-safe-global-public-health-strategy-to-fight-the-covid-19-pandemic-specific-micronutrient-composition-inhibits-coronavirus-cell-entry-receptor-ace2-expression

Select publications from other research institutions:

SARS-CoV-2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) has led to the coronavirus disease 2019 (COVID–19) pandemic, severely affecting public health and the global economy. Adaptive immunity plays a crucial role in fighting against SARS–CoV–2 infection and directly influences the clinical outcomes of patients. Clinical studies have indicated that patients with severe COVID–19 exhibit delayed and weak adaptive immune responses; however, the mechanism by which SARS–CoV–2 impedes adaptive immunity remains unclear. Here, by using an in vitro cell line, we report that the SARS–CoV–2 spike protein significantly inhibits DNA damage repair, which is required for effective V(D)J recombination in adaptive immunity. Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site. Our findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.

Hui Jiang, Ya-Fang Mei. Viruses,
2021 Oct 13;13(10):2056.
DOI: https://doi.org/10.3390/v13102056

Pilot trial of high-dose vitamin C in critically ill COVID-19 patients.

This pilot trial showed that HDIVC failed to improve IMVFD28, but might show a potential signal of benefit in oxygenation for critically ill patients with COVID-19 improving PaO2/FiO2 even though.

Jing Zhang et al., Ann. Intensive Care (2021) 11:5,
DOI: https://doi.org/10.1186/s13613-020-00792-3

The epidemiological relevance of the COVID-19-vaccinated population is increasing.

High COVID-19 vaccination rates were expected to reduce transmission of SARS-CoV-2 in populations by reducing the number of possible sources for transmission and thereby to reduce the burden of COVID-19 disease. Recent data, however, indicate that the epidemiological relevance of COVID-19 vaccinated individuals is increasing.

Gunter Kampf; The Lancet Regional Health – Europe, 11 (2021), 100272

Immune-mediated hepatitis with the Moderna vaccine, no longer a coincidence but confirmed.

This case illustrates immune-mediated hepatitis secondary to the Moderna vaccine, which on inadvertent re-exposure led to worsening liver injury with deranged synthetic function.

Gloria Shwe Zin Tun et al., J Hepatology, Published October 04, 2021,