Tuesday, April 02, 2024

Study Finds New Drugs Effective Against COVID-19 and Other Viruses

Studying the ways viruses impact cellular pathways during infection may help in developing treatments for infectious diseases such as COVID-19.

A new study, conducted by researchers at the University of Alberta and published in the npj Viruses journal found that certain cancer treatment drugs can promote cells to secrete antiviral interferons. These drugs target the SARS-CoV-2 virus, which causes COVID-19, and are also effective against multiple pathogenic RNA viruses.

Interferons are natural proteins that bolster the body’s immune system in combating infections and diseases like cancer. They earned their name because they interfere with viruses, stopping them from spreading.

Both COVID-19 and some cancers activate the Wnt/beta-catenin pathway—a chain reaction inside the cell. Drugs that block this pathway, originally made to treat cancer, might also help fight COVID-19.

When the Wnt/beta-catenin pathway gets activated, it slows down the production of interferons. This pathway also negatively impacts the immune system.

In a study, scientists tested two drugs, KYA1797K and E7449, that block the Wnt/beta-catenin pathway. They found that these drugs reduced the amount of virus in the lungs of mice. The drug E7449 was especially good at preventing weight loss and lung damage in the infected mice.

Tom Hobman, a professor of cell biology at the University of Alberta’s Faculty of Medicine and Dentistry and one of the study authors, explained in a press release that after using these drugs, cells produced interferons in response to viral infections at levels four to six times higher than before. Additionally, experiments also revealed that the virus was inactivated to less than one-ten-thousandth of its original levels.

He pointed out that interferons prevent infected cells from producing more viruses primarily in two ways, “It shuts down the infected cell, often resulting in cell death, and it also acts on the surrounding cells to prevent them from being infected.”

The researchers also tested viruses other than COVID-19 and found that the drugs exhibit broad-spectrum activity against a variety of RNA viruses. These include coronaviruses, responsible for seasonal respiratory infections, as well as mosquito-borne viruses like Zika and Mayaro.

Ongoing Drug Trials for COVID-19

In addition to drugs targeting the Wnt/β-catenin pathway, other drugs are also being explored for the potential to alleviate the COVID-19 virus.

A clinical trial published in February, which involved 1,821 mild to moderate COVID-19 patients, indicated that a drug called ensitrelvir significantly shortened the duration of symptoms in patients with COVID-19.

A phase II to III clinical trial of the anti-COVID-19 drug Simnotrelvir, involving 1,208 patients with mild to moderate COVID-19 infection, was published in the New England Journal of Medicine. The results showed that patients who received Simnotrelvir treatment within 72 hours of COVID-19 symptom onset had their “time to sustained resolution of symptoms” shortened by 35.8 hours. In a subgroup with risk factors for severe COVID-19, Simnotrelvir reduced the time by 60 hours.


Immunologists Call Out mRNA Vaccines—The Good, Bad & Ugly: Time to Go Back to Science

More data and analysis from various peer-reviewed journals raises serious concerns about the externalities associated with the mass countermeasures developed by the United States government in response to COVID-19. While the mRNA COVID-19 vaccines have been positioned as modern marvels of medicine—safety, effective and representative of the future of medicine, mounting literature not widely touted by American media implicates a different point of view.

Microbiologist and immunologist Botond Z. Igyártó, Ph.D., from Jefferson University in Philadelphia and immunology researcher Zhen Qin in the most recent edition of the peer-reviewed journal Frontiers in Immunology suggest the latest, accumulation of data points to the need for concern covering both safety and efficacy of the mRNA vaccines developed by Moderna in partnership with the National Institutes of Health and Pfizer in partnership with Germany’s BioNTech.

TrialSite has published article after article over the past couple years hinting at considerable challenges with mRNA platforms. The literature in the peer-reviewed journals amasses leading to questions for investors in the platform developers.

The authors herein call out for a security that represents an absolute must for the scientific community. With an unprecedented mass vaccination scheme via the use of an investigational product “that minimally protects from getting infected and spreading the virus during a pandemic,” the need for critical reflection becomes of paramount concern.

Was the strategy sound? Was her immunity a realistic expectation? Did the strategy as proposed by Geert Vanden Bossche lead to an actual acceleration of mutations? Should governments have focused on more vulnerable populations during the pandemic? Why was a novel mRNA platform opted for in the emergency over more known methods? Why focus on a single virus protein with a high mutation rate as TrialSite called out early on? Were the vaccine’s benefits (supposedly faster production, ease of updating for new variants, etc.) beneficial? Why did research leadership at the NIH for example ignore basic immunology knowledge during the pandemic?

Igyártó and Qin in this latest peer-reviewed output identify safety considerations, seeking to better understand the mechanisms of observed adverse events related to the mRNA jabs. Can such identified risk factors be mitigated by altering the mRNA platforms?

Describing the standard and non-standard components of the mRNA-LNP COVID-19 vaccines, Igyártó and Qin then address what the pair of authors describe as “concerning” assumptions made in regard to this technology.

While formally, the public has been told that mRNA vaccines do not allow for reverse transcription into DNA, meaning that there is no risk of insertion into the human genome, the authors raise some questions for consideration.

In particular instances, RNA can in fact be reverse transcribed into DNA. The authors note, “With the Pfizer mRNA-LNP vaccine, it has been shown experimentally that the vaccine mRNA can be reverse-transcribed into DNA in an immortalized human hepatocyte cell line.”

Also, the pair of authors note other possibilities for this concerning action, plus localization of the spike protein. A series of studies suggest the possibility of transcribed possibilities.

The authors point out:

“While to our knowledge similar studies have not been performed with COVID-19 mRNA vaccines that code for full-length pre-fusion fixed form of SARS-CoV-2 spike protein, comparable transport of spike protein/mRNA to the nucleus could be expected. Because the mRNA can enter the nucleus, where it might be reverse-transcribed into DNA, this increases its potential to integrate into the genome.

Furthermore, the mRNA-LNP diffuses throughout the body and can accumulate in both the testes and ovaries and is reported to alter the menstrual cycle in women. Therefore, it could potentially be reaching the stem cells of the reproductive organs. These findings highlight the need to take these data and concerns seriously and conduct specific experiments to address them.”

On the topic of the mRNA vaccine product degrading in vivo in hours or a matter of a few days, the authors challenge this misinformation to argue that the vaccines do not disrupt normal cell biology.

While it’s likely that this assumption (rapid product degradation) likely arose given that unmodified mRNAs have overall short in vivo half-life, real-world since points to a very different situation.

For example, “…human lymph node biopsies taken at different time points post-exposure to the mRNA-LNP revealed detectable levels of vaccine mRNA and spike proteins up to eight weeks.” And of course, TrialSite has reported on peer-reviewed data featuring the distribution and circulation of spike protein derived from the mRNA vaccines in humans for periods over a year.

Also, the effects of modified ribonucleotides (incorporated into the vaccine products to lower innate reactogenicity) just recently became more apparent.

Igyártó and Qin point out, “Incorporation of N1-methylpseudouridine into mRNA resulted in +1 ribosomal frameshifting in vitro and cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurred after vaccination.”

A key message from the authors on the overall topics: it’s dangerous to “assume and extrapolate in science” then apply existing paradigms to novel, untested platforms and technologies.

And just how safe and effective are the COVID-19 mRNA countermeasures?

Reviewing many of the same recent peer-reviewed journal entries, case reports and publicly available adverse event database as TrialSite, the current authors argue that this fact “cast doubts on the safety and effectiveness of these products.”

For example, on the topic of safety the authors point to a range of formidable entries calling out one concern to another. As TrialSite has editorialized many of the studies cited by Igyártó and Qin on the topic of COVID-19 mRNA vaccine safety suggest concern.

Similar outcomes can be found when probing efficacy. As the authors point out, “The effectiveness of these therapeutics in preventing infections and limiting the spreading of the virus has been highly eroded from the early reports, and nowadays, their efficacy is mainly limited to potentially decreasing the disease severity and death in susceptible people.” Pointing out that the efficacy that has been reported likens to the immune suppressive characteristics of these mRNA products, the authors urge for a “rigorous pre-clinical studies to limit potential unexpected consequences for novel platforms.”

Final Thoughts

Pointing out that “several fundamental questions persist surrounding the pandemic measures and the adoption of this new vaccine platform,” the scientists cogently argue “rather than advocating for retraction and censorship” rather there should be a movement in science to foster for open dialogue, considering all perspectives.

And for those that despite the findings above would still justify all that was done during the pandemic as the efforts saved lives, Igyártó and Qin point out that “the robustness of supporting data raises important inquiries.”

True trust is necessary to not undermine science and foster vaccine hesitancy, argue the authors of this important peer-reviewed paper. Seek to rebuild trust? Then, the authors argue it’s “crucial to return to the fundamental principles of scientific inquiry


Also see my other blogs. Main ones below:

http://edwatch.blogspot.com (EDUCATION WATCH)

http://antigreen.blogspot.com (GREENIE WATCH)

http://pcwatch.blogspot.com (POLITICAL CORRECTNESS WATCH)

http://australian-politics.blogspot.com (AUSTRALIAN POLITICS)

http://snorphty.blogspot.com (TONGUE-TIED)

https://immigwatch.blogspot.com (IMMIGRATION WATCH)

https://awesternheart.blogspot.com (THE PSYCHOLOGIST)

http://jonjayray.com/blogall.html More blogs


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