Friday Hope: Rutin: Inhibits SARS-CoV-2 Spike and Mpro: Cytotoxic to Cancer Cells

Rutin also has strong free radical scavenging properties and protects against DNA damage.

The Spike Protein of SARS-Cov-2 is widely known for causing inflammation, organ damage and other acute effects. It is also implicated in being a possible cause of oncogenesis.

The study has unveiled a remarkable phenomenon: the SARS-CoV-2 spike protein appears to disrupt the intricate balance of the p53 pathway, potentially compromising its tumor-suppressive capabilities. Through a series of meticulously designed experiments, the researchers demonstrated that the presence of the SARS-CoV-2 spike protein in cancer cells interferes with the binding of p53 to its negative regulator, MDM2.

This disruption, in turn, impedes the activation of key downstream targets of p53, including the cell cycle regulator p21(WAF1), the apoptosis-inducing TRAIL Death Receptor DR5, and even MDM2 itself. Consequently, cancer cells expressing the SARS-CoV-2 spike protein exhibited a diminished response to chemotherapeutic agents, manifested by a reduced induction of these critical p53 targets and an increased cell viability following treatment.

SARS-CoV-2 Spike Protein Disrupts p53 Tumor Suppressor Pathway
https://www.oncotarget.org/2024/05/09/sars-cov-2-spike-protein-disrupts-p53-tumor-suppressor-pathway/

Therefore, it is only logical that we would want to enhance the body’s ability to kill cancer cells post exposure to SARS-CoV-2 and its Spike Protein. In addition, it would also be very beneficial to prevent the Spike Protein from entering our cells and to prevent the SARS-CoV-2 virus from replicating.

Fortunately, Nature has provided a wonder-compound that accomplishes all of these tasks. It is called Rutin and it is a combination of quercetin (our old friend) and rutinose.

Rutin (rutoside, quercetin-3-O-rutinoside or sophorin) is the glycoside combining the flavonol quercetin and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose). It is a flavonoid glycoside found in a wide variety of plants, including citrus.

Rutin is a citrus flavonoid glycoside found in many plants, including buckwheat,[7] the leaves and petioles of Rheum species, and asparagus. Tartary buckwheat seeds have been found to contain more rutin (about 0.8–1.7% dry weight) than common buckwheat seeds (0.01% dry weight).[7] Rutin is one of the primary flavonols found in 'clingstone' peaches.[8] It is also found in green tea infusions.[9]

Rutin
https://en.wikipedia.org/wiki/Rutin

First, let’s examine how Rutin prevents the Spike Protein from entering our cells.

Rutin exhibits a good binding pattern to SARS-CoV-2 S1 subunit of S-protein (Fig. 5A),

The binding energy of −7.9 kcal/mol and inhibition constant of 5.81 μM (Table 1) and pi-pi stacking interaction by His519 and Phe565 with other pi-cation and pi-alkyl interactions helps in stabilizing the rutin bounded with the active residues of the S1 subunit. Rutin might be used as a potential inhibitor of spike protein as shown in Fig. 1, which could hinder the entry of the virus into the host cell.

Furthermore, not only may Rutin prevent the Spike from entering our cells, it also binds the main protease of the virus, preventing it from replicating.

After a detailed analysis of interactions of all the docked structures with Rutin, specific interactions have been found towards this SARS-CoV-2 Mpro, RdRp, PLpro, and S-protein binding pockets. The binding pattern of rutin with SARS-CoV-2 Mpro may hinder the substrate accessibility and its subsequent inhibition as shown in (Fig. 2A) where the binding energy and inhibition constant of −8.9 kcal/mol and 6.54 μM respectively (Table 1).

Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins
https://www.sciencedirect.com/science/article/pii/S2225411021000092

The above has been confirmed by additional studies, including one published November 22^nd.

Results

Of the tested compounds by virtual screening, rutin was identified as the best binding agent against the different proposed Mpro mutations. In addition, computational simulations and energy estimation analysis demonstrated the high structural and energetic stability between the Mpro-rutin systems.

Conclusions

Overall, our study identified rutin as the most promising compound with a strong affinity for various Mpro mutations, potentially playing a key role in the development of new treatments for emerging viral variants.

Identification of compounds from natural Peruvian sources as potential inhibitors of SARS-CoV-2 Mpro mutations by virtual screening and computational simulations
https://pmc.ncbi.nlm.nih.gov/articles/PMC11585855/

Rutin also possesses another superb ability – the ability to kill cancer cells. Whether a patient is a victim of Spike oncogenesis, or has developed cancer absent of the Spike, Rutin may prove to be a powerful ally in treating the disease. What is more encouraging is that Rutin appears to kill cancer cells without harming healthy cells.

And, as the proverbial “icing on the cake,” Rutin also scavenges free radicals and prevents DNA damage in healthy cells – while inducing DNA damage in cancer cells.

The capacity of Naringin and Rutin to provoke substantial cytotoxic effects in cancer cells, without causing injury to normal cells, corresponds with the therapeutic imperative of selectively targeting cancer cells while maintaining the integrity of healthy tissue.

The evaluation of antioxidant activity using the DPPH test provides further evidence of the dose-dependent effectiveness of Naringin and Rutin, highlighting an additional aspect of their therapeutic capabilities. Their ability to reduce oxidative stress and prevent DNA damage not only expands their usefulness in preventative approaches but also in therapeutic interventions for illnesses connected to oxidative stress, such as cancer.

Our work has discovered a new and important result on the oxidative DNA damage effects of Naringin and Rutin, specifically their ability to selectively induce DNA damage in breast cancer cells. At a dosage of 10 µM, this phenomenon of selective DNA base and strand breaks provides an opportunity for further investigation into the processes that allow these natural substances to successfully differentiate between malignant and non-cancerous cells.

Our study identifies Naringin and Rutin as very promising natural compounds with substantial therapeutic potential, particularly in the field of cancer therapy. Their ability to modify DDR, selectively kill cancer cells, serve as antioxidants, and cause DNA damage in cancer cells highlights the importance of conducting more research to fully understand their mechanisms of action and possible uses in therapeutic settings. This endeavor, though challenging, has the potential to advance cancer therapy by developing more precise, efficient, and less harmful treatment approaches, utilizing the subtle healing abilities of natural substances.

Assessing the antioxidant properties of Naringin and Rutin and investigating their oxidative DNA damage effects in breast cancer
https://www.nature.com/articles/s41598-024-63498-7

Every week increasingly shows us how eating well through a healthy balance of healthy foods provides our bodies the tools it needs to fight the Spike Protein of SARS-CoV-2 and the virus itself. On a personal note, I am increasingly distressed (I always have been, just more so now) by the preponderance of ultra processed foods. Eat well this weekend, and always. Be blessed and happy. We move forward with learning and hope.

I wish everyone warmth and happiness this weekend, especially in light of the frigid temperatures here in Northern Vermont. As always, immense thanks for your readership, dialogue and support.