Friday Hope: Curcumin II: Inhibiting SARS-CoV-2, its Spike Protein… and PRIONS

A new review highlights how Curcumin is almost certainly one of the most important supplements of our times.

Potential inhibitory effects of curcumin against the life cycle of zoonotic viruses and prions. The virus life cycle has different stages, including: (1) attachment, (2) entry, (3) viral genome replication/transcription, (4) translation/viral protein function, (5) assembly, and (6) release. Curcumin and its analogs disrupt many stages of the viral life cycle by inhibiting pathways and processes. By disabling the activity of viral envelope proteins, curcumin prevents viral entrance and adhesion in a variety of enveloped viruses. Curcumin also affects viral replication, whether by directly targeting the virus, or by interfering with the viral replication machinery by altering host cell signaling pathways such as NF-KB/MAPK PI3K-AKT, TLR 2/4, p38/c-JNK as well as transcription and translation factors, which subsequently prevent virus replication. CHIKV, Chikungunya Virus, DENV, Dengue virus, EBOV, Ebola virus, HTNV, Hantavirus, IAV, Influenza A virus, JEV, Japanese encephalitis virus, NiV, Nipah virus, ORF virus, Contagious ecthyma virus, RVFV, Rift Valley fever virus, SARS-CoV, Severe acute respiratory syndrome Coronavirus, SINV, Sindbis virus, VSV, vesicular stomatitis virus, ZIKV, Zika virus.

I have long been a believer in the use of curcumin in treating COVID and in its ability to treat Prionopathies. In June of 2022 I wrote a post (as I have also long stated my hypothesis, unfortunately being proved true, that the Spike Protein induces Prionopathies) discussing how quercetin and curcumin could be powerful “prioloid” therapeutics.

QUERCETIN AND CURCUMIN AS POTENTIALLY POWERFUL "PRIOLOID" THERAPEUTICS
https://wmcresearch.substack.com/p/quercetin-and-curcumin-as-potentially

A review article, published last week in the journal Phytotherapy Research, definitively shows that curcumin is, indeed, a potentially (and mostly proven) very powerful therapeutic in treating both COVID and Prion Disease. At this point, I personally view Vitamin D and Curcumin as perhaps the two “desert island” supplements I would absolutely select.

Curcumin has been used for centuries in traditional medicine and has become the subject of much (very hopeful) research over the past 20 years.

Curcumin, the active ingredient of turmeric (Curcuma Soma, Fam-ily: Zingiberaceae) which is native to the Indian subcontinent and southeast Asia, has been vastly used in traditional medicine for centuries. Curcumin has been extensively investigated in the last two decades, indicating its numerous medicinal properties in treating various disorders. These properties, along the related curcuminoid family, include anti-microbial, anti-vascular (substances that target the blood vessels of tumors or some diseases), anti-inflammatory, anti-tumor, anti-neoplastic (substances that are used to target cancer cells), anti-oxidant, immune system modulator, and wound healing activities (Aggarwal & Harikumar, 2009; Saifi et al., 2022; Zorofchian Moghadamtousi et al., 2014). Notably, there is no considerable report indicating dangerous toxicity of this substance in humans (Jafari-Nozad et al., 2022). Curcumin exerts its anti-inflammatory and anti-oxidant effects by interacting with different signaling molecules and transcription factors (Momtazi et al., 2016). Anti-angiogenic and anti-tumor effects of this compound are accomplished by stopping the cell cycle and inducing apoptosis through mitochondria! and other path-ways (Barati et al., 2019; Morshedi et al., 2021). Regulatory activity of the immune system by curcumin shows its effect on various immune cells (Abdollahi et al., 2018); in addition, by different means including affecting transcription factors and microRNAs, cytokines, inflammation-related enzymes, protein kinases, and redox status, cur-cumin has shown to be effective in the treatment and/or prevention of neurological, cardiovascular, renal, metabolic, and auto-immune diseases (Abdollahi et al., 2018; Aggarwal & Harikumar, 2009; Momtazi et al., 2016).

Looking at COVID, curcumin appears almost tailor-made to treat the disease. From inhibiting the expression of inflammatory cytokines and targeting the Spike Proetein to completely eliminating SARS-CoV-2 from cell cultures, curcumin offers a plethora of healing properties. Furthermore,  it is absolutely safe and effective with virtually no known toxicity.

A large number of existing recent studies in the literature have examined the effects of curcumin against SARS-CoV-2. Using in vitro method, it has been shown that curcumin inhibits SARS-CoV-2. The body of evidence revealed inhibition of different pathways including NF-KB/MAPK, cytokines production, as well as oxidative stress. Many proteins are targeted by curcumin which shed light on curcumin's inhibitory properties. For example, viral spike protein (specially RBD domain) and viral membrane protein, as well as RNA-dependent RNA polymerase (which is a key part of the virus replication and transcription machinery) have been blocked and inhibited by curcumin and its different components. Some investigations concluded that curcumin/curcuminoids have inhibitory effects against Alpha, Beta, Gamma, Delta, Kappa Mu, and omicron variants of the virus. According to some reports, curcumin was able to completely eliminate the SARS-CoV-2 from cell cultures, and reduce viral RNA load by a maximum of 87.8%. Besides, curcumin reduced C reactive protein levels significantly. Some studies have driven the further development of curcumin's derivatives to enhance the delivery and effectiveness. For instance, Aspirin-curcumin mimic, nano-curcumin, and Silymarin + Curcumin showed higher antiviral characters. In vivo investigations are other promising lines of research. The in vivo studies have shown several advantages: 1. Curcumin would ameliorate the disease symptoms such as cough, inflammation, pain, and disturbance in the sense of taste and smell; 2. Curcumin could significantly improve recovery time in patients with mild to moderate COVID-19; 3. Curcumin would modulate the immune system; 4. Cytokine storm would subside with curcumin supplements; 5. The average antibody formed in groups treated with curcumin supplementation showed a statistically significant increase compared to the control group. Slightly superior results are achieved with curcumin's nano conjugates. Nano-curcumin could significantly increase the frequency of Treg cells, the expression levels of FoxP3, IL-10, IL-35, and TGF-b (all of these factors would help the suppression of the inflammation) in both mild and severe COVID-19 patients. On the other hand, mRNA expression of the inflammatory cytokines such as IL-1, IL-2, IL-6, IL-18, IFNs, and TNFs were considerably decreased. Also, other studies have shown that nano-curcumin may be effective in increasing 02 saturation and reducing the severity of symptoms in COVID-19 patients. Nano-formulation of curcumin could significantly improve the symptoms caused by COVID-19 and oxygenation. It could also reduce hospital stay. Moreover, no significant side effects have been reported with nano-curcumin. In addition, in silico methods illustrated that curcumin targeted several viral and host proteins (membrane protein, spike protein, 3CLprotein, NSPs, ACE2 nucleocapsid, TMPRSS2 and many others) to block the viral cycle, as well as host immune response.

Furthermore, curcumin possesses strong anti-prion properties. As we are assailed not only by the Spike Protein’s prionopathic properties, there are other threats, such as the now confirmed deer-to-human transmission of CWD in a hunter that consumed an infected deer. This makes curcumin all the more critical.

Studies conducted on the anti-prion properties of curcumin are well documented. The existing considerable body of literature have demonstrated that curcumin prevented PrPsc aggregation, decreased the formation of amyloid fibrils, disaggregated the alpha and beta-amyloid structures, delayed the onset of fibril formation, and slowed the growth of fibrils. An experimental study on the animal model illustrated that low but not high-dose treated mice survived longer than untreated controls. Compactional studies targeting ab fibrils by curcumin also revealed acceptable docking scores.

The above three quotes are from the aforementioned astounding review article.

Curcumin as a natural potential drug candidate against important zoonotic viruses and prions: A narrative review
https://onlinelibrary.wiley.com/doi/10.1002/ptr.8119

I wish all a very hopeful and happy Spring weekend. Chicken Tikka Masala is certainly in order! Thank you, as always, for your continued support, readership and dialog.