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Could cat drugs treat humans with COVID-19?

Two experimental drugs for cats could potentially help treat humans infected with COVID-19, Science News reported.

A type of coronavirus that only infects cats can cause "feline enteric coronavirus" (FeCV), an infection that affects the gastrointestinal tract and seldom causes any symptoms, according to the Cornell University College of Veterinary Medicine. However, in about one in 10 infected cats, the virus mutates after infecting the animal in a way that lets it infiltrate specific immune cells, spread throughout the body and set off severe inflammation. At this stage, the infection is called "feline infectious peritonitis virus" (FIPV) and is usually fatal if left untreated.

Two experimental drugs have been designed to treat cats with FIPV, although neither has been approved by the U.S. Food and Drug Administration (FDA), which vets both animal and human drugs before they enter the market, according to Science News. That said, preliminary research hints that both drugs could be used to take down human coronaviruses, including SARS-CoV-2, the virus that causes COVID-19.

Related: Treatments for COVID-19: Drugs being tested against the coronavirus 

"The fact that this drug has already been developed and shown to be successful in treating feline infectious peritonitis, it really bodes well," biochemist Joanne Lemieux told Science News about one of the drugs, called GC376. The second drug, called GS-441524, has also been found to be "highly effective in curing cats with feline infectious peritonitis, and usually without any other form of treatment,” Niels Pedersen, a veterinarian who studies the feline coronavirus at the University of California, Davis, told Science News.

The two drugs work by preventing the feline coronavirus from replicating in cat cells; it  may also disrupt how SARS-CoV-2 replicates in human cells.

GC376, for example, hobbles a key enzyme called M protease that the feline coronavirus relies on to help make copies of its genetic material, known as RNA. While replicating, the virus builds long strands of proteins that M protease then chops up, to separate each individual protein from the next in the chain. The individual proteins then come together to build a new copy of the coronavirus. And so if  M protease is damaged, the feline coronavirus cannot replicate and continue to make cats sick.

Other coronaviruses, including SARS-CoV-2, also use M protease to build copies of the virus. A 2016 study, published in the journal PLOS Pathogens, revealed that GC376 also stops M protease from working in SAR-CoV and MERS-CoV, two coronaviruses that caused outbreaks of respiratory disease in humans in the 2000s. This year, a study in the journal Cell Research suggested that the drug can also stop SARS-CoV-2 from replicating in a test tube, while another study showed similar results in lab-grown monkey cells, according to Science News.

Based on these results, Anivive Lifesciences, the company that manufactures GC376, plans to test the drug in human trials for use as a COVID-19 treatment. 

Related: 20 of the worst epidemics and pandemics in history

The second experimental cat drug, GS-441524, has shown similar success in animal studies of SARS-CoV-2, Science News reported. The drug works similarly to remdesivir, the antiviral shown to reduce recovery time in hospitalized COVID-19 patients. "Partly because of feline infectious peritonitis research, a lot of veterinarians seemed to realize early in the course of the COVID-19 pandemic that remdesivir could be a promising candidate" for COVID-19 treatment in humans, Susan Amirian, a molecular epidemiologist at Rice University in Houston, told Science News.

Both drugs share a similar chemical structure that resembles a segment of viral RNA — molecules known as nucleotides that link up to form both RNA and DNA. When exposed to either drug, coronavirus enzymes wedge the molecule into the viral RNA in place of a true nucleotide, which brings viral replication to a standstill. Note that the drugs only work with RNA-virus enzymes, rather than human enzymes, so they don't mess up human DNA replication, according to the Scope Blog, published by Stanford Medicine.

A study published in the journal Cell Reports showed that, in addition to stopping feline coronavirus, GS-441524 can also keep SARS-CoV-2 from replicating in lab-grown monkey and human cells. However, GS-441524 was most effective in the monkey cells, while remdesivir worked better than GS-441524 in human lung cells, according to Science News.

The biopharmaceutical company Gilead Sciences designed both remdesivir and GS-441524 and has begun early studies to compare the effects of both drugs against SARS-CoV-2, company spokesperson Chris Ridley told Science News.

Previously, the company stated that it chose to focus on remdesivir over GS-441524 at the start of the pandemic because remdesivir had already been tested in human safety trials as an antiviral treatment for Ebola, which the drug didn't treat effectively, according to Science News. While testing remdesivir for Ebola, Gilead decided not to seek approval for GS-441524 use in animals because the drug so closely resembled remdesivir and may have somehow influenced the FDA-approval process, according to The Atlantic. Even now, GS-441524 has not been approved for use in cats and is usually bought as an expensive, black-market formulation, The Atlantic reported.

At this point, neither GS-441524 nor GC376 have been tested in humans at all.

Originally published on Live Science. 

  • Chem721
    Does anyone know how remdesivir was designed, or if it was? Was it by knowledge of the viral enzyme's structure that was different from the various human polymerase active sites?

    It is quite remarkable to deliver an adenosine nucleoside analog that gets converted to a triphosphate inactivating agent specific to the viral mechanism, and shuts it down. Avoiding an impact on similar mechanisms in the host is particularly remarkable. Perhaps it was developed by combinatorial chemistry, assuming that is still alive and well.
    Reply
  • adam
    Chem721 said:
    Does anyone know how remdesivir was designed, or if it was? Was it by knowledge of the viral enzyme's structure that was different from the various human polymerase active sites?

    It is quite remarkable to deliver an adenosine nucleoside analog that gets converted to a triphosphate inactivating agent specific to the viral mechanism, and shuts it down. Avoiding an impact on similar mechanisms in the host is particularly remarkable. Perhaps it was developed by combinatorial chemistry, assuming that is still alive and well.

    Remdesivir (GS-5734) produces a main metabolite GS-441524 which is also another Gilead drug developed around the same time in 2009. GS-441524 is less toxic than remdesivir (GS-5734)

    Remdesivir's parent nucleoside is GS-441524 which is another separate Gilead drug. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs.

    Some questions have been raised about Gileads patent over GS-441524 so Gilead many feel Remdesivir is a more secure patent.

    Gilead has not include the FDA in its remdesivir patent filings when the published research shows the FDA was involved in much of the critical r&d and should be jointly on the patent.

    Gilead has for many years blocked research, development or production of it drug GS-441524 for humans or animals even though it proved 100% effective in curing the 100% fatal cat coronavirus FIP - during clinical trials at the University of California and in subsequent application to pet cats with FIP 25 out of 31 recovered

    Links to my previous posts with links to the peer reviewed published research and links to other info is at the end of this post.

    Gilead and the FDA have not been helpful about providing research info on GS-441524 with the FDA being forced by an open letter to Gilead and the FDA into admitting in writing in August that old research into GS-441524 showed it was a drug with significant potential as a Covid-19 treatment.


    Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 TreatmentVictoria C. Yan*and
    Florian L. MullerCite this: ACS Med. Chem. Lett. 2020, 11, 7, 1361–1366
    Publication Date:June 23, 2020
    https://doi.org/10.1021/acsmedchemlett.0c00316Copyright © 2020 American Chemical Society
    While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and in vivo efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.
    KEYWORDS:
    ProdrugCovid-19remdesivirWhile remdesivir has demonstrated efficacy against Covid-19, its broad translational applicability has been hampered by limited supply and distribution(1) due to the difficulty of its synthesis(2) and its obligatory intravenous (IV) administration requiring an inpatient setting. We recently described in a general audience publication(3) the advantages that the parent nucleoside of remdesivir, GS-441524, has over remdesivir itself for the treatment of Covid-19. Fundamentally, our investigation into the metabolism of remdesivir evidences premature serum hydrolysis of its phosphate prodrug, followed by dephosphorylation.(4−6) As a result, the major metabolite circulating in the bloodstream is the parent nucleoside, GS-441524, even though remdesivir (monophosphate nucleotide prodrug) was the species initially administered. Accounting for this broader pharmacokinetic (PK) rationale, we herein provide a detailed analysis of the literature that supports the use of GS-441524 over remdesivir for the treatment of Covid-19.

    The Phosphate Prodrug on Remdesivir Is Not Intended for Lung-Specific DeliveryRemdesivir is a structural analogue of adenosine monophosphate (AMP) that interferes with the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).(7) The anionic phosphate moiety on remdesivir is masked by McGuigan prodrug moieties(8) (phenol and l-alaninate ethylbutyl ester) to enhance cell permeability. In principle, these prodrug moieties would be removed intracellularly—first by esterases (cathepsin A/carboxylesterase 1) and then by phosphoramidases (HINT1-3)(9) to release the monophosphorylated nucleotide. This would then be phosphorylated twice to give the active NTP(7,9) (Figure 1a), which is substrate-competitive with ATP for........

    etc see link below for full text


    GS-441524 Is Exceptionally Effective and Well-Tolerated against Clinical Presentations of Feline CoronavirusThere are currently no studies that have compared the antiviral activities of remdesivir and GS-441524 in vivo, with most focusing exclusively on remdesivir. Where GS-441524 has been investigated in vivo is in the veterinary setting.(21−23) Cats infected with feline coronavirus (FCoV) present with a serious disease known as feline infectious peritonitis (FIP). While long considered fatal in its severe manifestations,(24) a study conducted by Pedersen and colleagues showed that GS-441524 is capable of treating cats suffering from FIP with a 96% cure rate.(21) Pedersen noted the “impressive” safety profile of GS-441524, with no systemic signs of toxicity observed when administered subcutaneously at 4 mg/kg.(21) In a more recent study, Pedersen and colleagues escalated the dose of GS-441524 (5–10 mg/kg) to treat neurological manifestations of FIP; this translates to about 350–700 mg in a 70 kg human, greatly exceeding the dose currently given to patients treated with remdesivir (200 mg loading, then 100 mg).(13,25) Even at these higher doses, they found that GS-441524 treatment resulted in the long term resolution of neurological FIP with an excellent safety profile: minimal dose-related toxicities were observed.(23)
    GS-441524 Shows Comparable Efficacy in Cell-Based Models of Primary Human Lung and Cat Cells Infected with CoronavirusIn vitro potency comparisons between GS-441524 and remdesivir are ultimately moot in the context of respiratory diseases such as SARS-CoV-2, if GS-441524 is the predominant species that reaches the lungs. To better gauge the efficacy of GS-441524 against SARS-CoV-2, it is helpful to first compare EC50 values between coronavirus infected human and cat cells, as the clinical efficacy of GS-441524 has already been well-established in cats.(21) GS-441524 has an EC50 value of 0.78 μM in CRFK cells infected with FCoV (Figure 3a).(26) At the time of publication, a study by Agostini and colleagues is the only report that has compared the antiviral activities of GS-441524 and remdesivir in primary human airway epithelial (HAE) cells, the most clinically relevant in vitro model of the lung, infected with either SARS-CoV or MERS-CoV.(27) While the mean EC50 value of remdesivir is lower for both SARS-CoV and MERS-CoV-infected cells, close inspection of the data reveals large standard deviations between the EC50 values obtained from GS-441524 and remdesivir making these potency differences not statistically significant (Figure 3a).(27) For instance, against SARS-CoV-infected HAE cells, GS-441524 has a reported EC50 of 0.18 (±0.14) μM, which is comparable, if not lower, than that required to exert antiviral activity against FCoV-infected cells in vitro. Most significantly, the EC50 concentration for GS-441524 against SARS-CoV-infected primary HAE cells is sustained in the plasma of NHP for nearly the entire duration of the single-dose, 24 h PK experiment conducted by Warren and colleagues (Figure 3c). In contrast, the EC50 concentration for remdesivir against SARS-CoV-infected primary HAE cells diminishes after ∼2 h. The dominance of GS-441524 over remdesivir in serum was even more pronounced in Williamson’s 7-day PK study, in which GS-441524 was present in serum at concentrations 1,000-fold greater than remdesivir at every measured time point (Figure 3b).(6) Coupled with the robust antiviral activity that GS-441524 has demonstrated against FIP, these data compel further investigations into the therapeutic and prophylactic utility of GS-441524 against SARS-CoV-2 in patients.


    Concluding RemarksJump ToSARS-CoV-2 is a respiratory virus that primarily affects the lungs.(12) While remdesivir has shown some efficacy in patients with advanced Covid-19,(13) its phosphate prodrug is fundamentally not designed for lung-specific delivery. Enzymes that activate the McGuigan prodrug are preferentially expressed in tissues such as the liver, which results in uneven distribution of active NTP formation via remdesivir that disfavors the lungs. Practically, the structural complexity of the McGuigan prodrug(28) adds unnecessary synthetic difficulty that hampers mass production and impedes distribution.......


    https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00316
    Some researchers have suggested Gs-441524 utility as a treatment for COVID-19 and pointed out advantages over Remdesivir, including lack of on-target liver toxicity, longer half-life and exposure (AUC) and much cheaper and simpler synthesis. Some counter questions have been raised about its effectiveness in primates :

    "Prediction of human oral bioavailability from pre-clinical data is more art than science, and relies on modeling data from multiple species."

    Gileads long term position has been to refuse to allow any development of GS-44152 even though clinical trials showed its 100% effectiveness against a 100% fatal coronavirus


    https://en.m.wikipedia.org/wiki/GS-441524
    https://en.m.wikipedia.org/wiki/Remdesivir

    There appear to be some questions about how strong Gileads patent on GS-441524 is so it might have been a way of producing a more secure "new" patent.

    GILEAD owns patent rights to GS-441524 (2009) and Remdesivir (2017); The 2009 patent of GS-441524 may be invalid due to prior art: as we have seen in the GILEAD vs MERK trial (which Merk initially won), there is a large amount of prior art in the nucleoside space that may invalidate the GS-441524 patent.

    https://www.patentoppositions.org/en/call_for_helps/5ed283dfd2708f000553d358


    Previous Posts on GS-441524
    https://forums.livescience.com/threads/please-explain-why-anivives-gc376-has-been-fast-tracked-over-gileads-gs-441524-for-covid-19-clinical-trials.3804/
    https://forums.livescience.com/threads/coronavirus-gs-441524-a-promising-covid-19-treatment-stalled-will-gilead-and-the-fda-help-texas-university-cancer-researchers-find-out-the-truth.3463/
    Reply
  • sarajo
    admin said:
    Two experimental drugs for feline coronavirus could show promise against COVID-19.

    Could cat drugs treat humans with COVID-19? : Read more
    How bizzare!! what a load of rubbish theres no evidence at all!!! If the answer was yes it would be all over the news internationally & everyone would want a supply
    Reply
  • adam
    sarajo said:
    How bizzare!! what a load of rubbish theres no evidence at all!!! If the answer was yes it would be all over the news internationally & everyone would want a supply

    admin said:
    Two experimental drugs for feline coronavirus could show promise against COVID-19.

    Could cat drugs treat humans with COVID-19? : Read more


    The FDA had confirmed in writing that they will now urgently investigate the drug GS-441524 as a Covid-19 treatment

    See the Public Citizen link below for links to the pdfs of the open letters to and from the FDA and Gilead about this. No explaination was provided about why no research had been done to date

    See also previous posts on GS-441524 in live science with links to the current research and previous clinical trials, animal tests and unofficial use which have then been blocked by Gilead from being applied despite a near 100% cure rate for a 100% fatal cat coronavirus


    WASHINGTON, D.C. – The National Institutes of Health (NIH) will expeditiously conduct preclinical studies of GS-441524 as a treatment for COVID-19 and will make the results readily available to the scientific community, as requested in a letter sent to the agency by Public Citizen.

    On Aug. 4, Public Citizen and two university-based drug researchers urged Gilead Sciences, Inc. and several government agencies, including the NIH, to advance development of GS-441524 as a potential treatment for COVID-19, because evidence shows it may offer significant advantages over the closely related antiviral drug remdesivir.

    ......director of the NIH’s National Center for Advancing Translational Sciences, Dr. Christopher Austin, on Aug. 22, stating that “Scientists in our Division of Preclinical Innovation have reviewed the literature and agree that merits further exploration,” and that NIH scientists will quickly conduct preclinical studies of the drug.

    “Public Citizen applauds the NIH’s commitment to conducting the necessary preclinical studies of GS-441524 as a potential treatment for COVID-19, and we await those results with great anticipation,” said Michael Abrams, health researcher at Public Citizen and lead author of the letter. “Such further study of the drug is long overdue, especially given the evidence that GS-441524 may be cheaper and easier to manufacture and more amenable to administration in inhaled or oral forms than remdesivir.”


    https://www.citizen.org/news/nih-agrees-with-public-citizen-will-conduct-preclinical-trials-of-the-potential-covid-19-treatment-gs-441524/

    Gilead and the University of California jointly own the patent of GS-441524 the fatal cat corona virus cure also effective against coronaviruses SARS and MERS

    Gilead currently holds 100% of the patent for Remdesivir the FDA approved treatment for Covid-19

    Gilead has blocked the use of GS-441524 and failed to co-operate with University researchers looking at GS-441524 as a Covid-19 treatment, even though it is the only effective cure for the fatal cat corona virus FIP as shown by clinical trials carried out at the University of California, and is also effective against MERS and SARS

    There is a good background article below and there is extensive medical research linked in the links at the end

    https://www.theatlantic.com/science/archive/2020/05/remdesivir-cats/611341/
    Previous posts and links to news and medical research


    https://forums.livescience.com/threads/please-explain-why-anivives-gc376-has-been-fast-tracked-over-gileads-gs-441524-for-covid-19-clinical-trials.3804/
    https://forums.livescience.com/threads/coronavirus-gs-441524-a-promising-covid-19-treatment-stalled-will-gilead-and-the-fda-help-texas-university-cancer-researchers-find-out-the-truth.3463/
    Reply
  • adam
    A recent public posting on 17th September 2020 by a legal firm (Kershaw, Cook & Talley) on its web site about ongoing litigation confirms that Gilead has a history of withholding more effective less harmful drugs it owns, developed at the same time, for commercial reasons - and only releasing the better drug 15 years later as a new improved treatment once the more toxic and damaging drug was nearing the end of its patent life

    Kershaw, Cook & Talley - statements and comments

    Gilead Sciences, Inc. and the federal government have been accused of withholding a promising treatment for COVID-19, also known as the coronavirus, that may offer “significant advantages” over Remdesivir, currently Gilead’s sole drug undergoing clinical trials for COVID-19 treatment, according to Public Citizen, a non-profit consumer advocacy organization. Kershaw, Cook & Talley is actively pursuing a lawsuit alleging that Gilead engaged in nearly identical conduct regarding the marketing of TDF- and TAF-based drugs used in the treatment and prevention of HIV infection over 20 years earlier.

    The allegations Public Citizen brought forward concerning Gilead’s conduct with respect to Remdesivir and GS-441524 is remarkably similar to its alleged conduct in a lawsuit pending in San Francisco Superior Court on behalf of thousands of individuals represented by Kershaw, Cook & Talley and other law firms across the United States. In this lawsuit, plaintiffs allege that Gilead developed TDF-based drugs — commonly known as Viread®, Truvada®, Truvada for PrEP®, Atripla®, Complera® and Stribild® — for the treatment and prevention of HIV infection, while it simultaneously developed TAF-based drugs proved to be safer and at least equally effective at much smaller doses. Gilead’s own studies demonstrated that TDF had a much higher risk of severe side effects, including bone loss and kidney failure. Gilead chose to sell TDF and kept TAF (the safer drug) off the market for nearly 15 years. Plaintiffs allege that this strategy was enacted solely to maximize Gilead’s profits and extend its patent protection for these life-saving drugs. Once the patent on TDF ran out, Gilead then came out with TAF and marketed it as a “new and improved” drug with fewer side effects than TDF.

    To date, almost 18,000 plaintiffs have filed lawsuits against Gilead, which have been consolidated in San Francisco Superior Court for pretrial discovery.

    In an August 4 letter, Public Citizen and scientists at MD Anderson Cancer Center alleged that both Gilead and the U.S. Department of Health and Human Services (HHS) have been sitting on a drug known as GS-441524 despite the fact that it has shown superior antiviral behavior against the coronavirus in cell cultures compared to Remdesivir. Gilead is accused of keeping GS-441524 on the shelf in order to extend its monopoly over drugs that can be used to treat COVID-19.

    PDF full text of open letter and supporting info to FDA and Gilead

    https://www.citizen.org/wp-content/uploads/2535.pdf?eType=EmailBlastContent&eId=ab7987b8-616e-4966-b5dd-5b9d7fd0c85c&eType=EmailBlastContent&eId=ab7987b8-616e-4966-b5dd-5b9d7fd0c85c
    “It is sadly predictable that Big Pharma responds to a global pandemic by trying to bring to market only those drugs that maximize its profits,” said Michael Abrams, health researcher with Public Citizen’s Health Research Group and lead author of the letter. “What is alarming here is that federal scientists and Trump administration regulators appear to be willing partners with Gilead in decisions that run distinctly counter to the government’s primary imperative of advancing public health during this worldwide crisis.”

    Kershaw, Cook & Talley

    https://www.kctlegal.com/blog/2020/september/gilead-allegedly-withholds-safer-more-effective-/
    Reply
  • sarajo
    adam said:
    The FDA had confirmed in writing that they will now urgently investigate the drug GS-441524 as a Covid-19 treatment

    See the Public Citizen link below for links to the pdfs of the open letters to and from the FDA and Gilead about this. No explaination was provided about why no research had been done to date

    See also previous posts on GS-441524 in live science with links to the current research and previous clinical trials, animal tests and unofficial use which have then been blocked by Gilead from being applied despite a near 100% cure rate for a 100% fatal cat coronavirus


    WASHINGTON, D.C. – The National Institutes of Health (NIH) will expeditiously conduct preclinical studies of GS-441524 as a treatment for COVID-19 and will make the results readily available to the scientific community, as requested in a letter sent to the agency by Public Citizen.

    On Aug. 4, Public Citizen and two university-based drug researchers urged Gilead Sciences, Inc. and several government agencies, including the NIH, to advance development of GS-441524 as a potential treatment for COVID-19, because evidence shows it may offer significant advantages over the closely related antiviral drug remdesivir.

    ......director of the NIH’s National Center for Advancing Translational Sciences, Dr. Christopher Austin, on Aug. 22, stating that “Scientists in our Division of Preclinical Innovation have reviewed the literature and agree that merits further exploration,” and that NIH scientists will quickly conduct preclinical studies of the drug.

    “Public Citizen applauds the NIH’s commitment to conducting the necessary preclinical studies of GS-441524 as a potential treatment for COVID-19, and we await those results with great anticipation,” said Michael Abrams, health researcher at Public Citizen and lead author of the letter. “Such further study of the drug is long overdue, especially given the evidence that GS-441524 may be cheaper and easier to manufacture and more amenable to administration in inhaled or oral forms than remdesivir.”


    https://www.citizen.org/news/nih-agrees-with-public-citizen-will-conduct-preclinical-trials-of-the-potential-covid-19-treatment-gs-441524/

    Gilead and the University of California jointly own the patent of GS-441524 the fatal cat corona virus cure also effective against coronaviruses SARS and MERS

    Gilead currently holds 100% of the patent for Remdesivir the FDA approved treatment for Covid-19

    Gilead has blocked the use of GS-441524 and failed to co-operate with University researchers looking at GS-441524 as a Covid-19 treatment, even though it is the only effective cure for the fatal cat corona virus FIP as shown by clinical trials carried out at the University of California, and is also effective against MERS and SARS

    There is a good background article below and there is extensive medical research linked in the links at the end

    https://www.theatlantic.com/science/archive/2020/05/remdesivir-cats/611341/
    Previous posts and links to news and medical research


    https://forums.livescience.com/threads/please-explain-why-anivives-gc376-has-been-fast-tracked-over-gileads-gs-441524-for-covid-19-clinical-trials.3804/
    https://forums.livescience.com/threads/coronavirus-gs-441524-a-promising-covid-19-treatment-stalled-will-gilead-and-the-fda-help-texas-university-cancer-researchers-find-out-the-truth.3463/
    My apologies -with respect despite what has been confirmed in writing over there -if it becomes a reality in the UK then I probably would carefully consider believing it .With respect I stick to my statement of opinion -apologies again
    Reply
  • adam
    sarajo said:
    My apologies -with respect despite what has been confirmed in writing over there -if it becomes a reality in the UK then I probably would carefully consider believing it .With respect I stick to my statement of opinion -apologies again

    No need to apologize - everyone is free to make thier own decisions - however the "cat drug" is already effectively in the UK via Gileads drug remdesivir.

    I hope the info below is useful.

    What Gilead admits in its research but is not made clear generally by Gilead, who controls both drugs, is that Remdesivir is converted into the "cat drug" GS-441524 in the human body and that GS-441524 is the effective medical compound fighting Covid-19

    So GS-441524 is already in patients the UK NHS as the UK has approved Remdesivir as a Covid-19 treatment - though it is in very short supply.

    https://www.bbc.com/news/health-52805828
    Further both drugs - GS-441524 and Remdesivir - are almost identical chemically - Remdesivir has about 2 extra molecules and has certain toxic properties Vs GS-441524.

    Clinical and animal trials show taking GS-441524 directly is much less toxic than taking Remdesivir and the body converting Remdesivir into GS-441524

    Given both Remdesivir and GS-441524 produce the same active metabolite (GS-441524 triphosphate) which acts against Covid-19 why add unneeded toxicity to a weak body by taking Remdesivir?

    Generally Remdesivir looks less effective at the same dosage as GS-441524 and cannot be taken in high doses, is much more difficult to produce and give to patients and is definitely much more expensive

    We know GS-441524 cures cats of a 100% fatal coronavirus and was effective againsts SARS and MERS , however Gilead does not own 100% of the patent and refused to allow GS-441524 to be legally used to cure cats of a fatal coronavirus despite amazing clinical trial results and repeated requests - probably to make sure there was no competition against Remdesivir (previously being tested by the FDA and Gilead against ebola but failing - with FDA approval withdrawn in August 2019?)

    Gilead has acted badly numerous times in the past, even doing much the same as now with Remdesivir Vs GS-441524 with another drug as set out below.

    Gilead is being sued for developing 2 HIV drugs at the same time but withholding the less toxic and more effective HIV drug for 15 years it appears just to make more money - Gilead only released the better drug once the old more toxic patent expired despite all the time having the research data showing the lesser toxicity and better effectiveness etc

    See the link in my second post of today below for the HIV drug legal case - just found that out today.

    https://forums.livescience.com/threads/could-cat-drugs-treat-humans-with-covid-19.3313/post-14638
    Gilead also tried to use FDA patents without paying and is being sued by the FDA with at least US$ 1 Billion in patent payment claims being referred to in the UK FT. Also in the link above.

    Commercially Gilead would make a big killing if it sold large amounts of Remdesivir now and then later found a better drug to treat Covid-19. What would governments do ?

    In summary taking GS-441524 directly is much less toxic than Remdesivir and has many other benefits including being cheaper, can probably be taken in tablet form, and is probably more effective etc - yet Gilead and the FDA did not research it ???

    How is this possible when

    1. Covid-19 clinical research shows that after Remdesivir was administered intravenously the researchers found that only GS-441524 — not remdesivir — was detected in the macaques’ lungs, and they exhibited no signs of respiratory disease, a significantly reduced viral loads, and had a distinct reduction in damage to lung tissue.

    2. In the study using GS-441524 to treat feline coronavirus, the researchers noted its “impressive” safety profile when administered at high doses, and reported that no systemic signs of toxicity were observed over 12 to 30 weeks of treatment.

    3. Remdesivir cannot be used in the same high doses because of its toxicity

    4. Patients with advanced or severe Covid-19 generally have a high viral load in their lungs and would need a high concentration of GS-441524 triphosphate to combat it.

    5. The benefit of using GS-441524 over Remdesivir is that GS-441524 can almost certainly be given at much higher doses due to its lower toxicity. This would result in more conversion to the active compound, GS-441524 triphosphate, in the lungs.

    The Q&A after the article below is very good and extensive, with questions from many parties including some critical of the GS-441524 researchers which are addressed very helpfully

    https://www.statnews.com/2020/05/14/gilead-should-ditch-remdesivir-and-focus-on-its-simpler-safer-ancestor/comment-page-3/#comments

    Conclusion

    What seems clear is that Gilead and the FDA cannot and have not explained why no FDA or Gilead research has been done on GS-441524 (side by side with remdesivir or otherwise) or why other researchers have been obstructed by Gilead from researching GS-441524 separately

    See link below on Gilead political lobbying profile in 2020

    https://www.npr.org/sections/health-shots/2020/05/02/849149873/gilead-lobbying-rose-as-interest-in-covid-19-treatment-climbed
    Finally just in 2019 phrama/healthcare companies spent $30 Billion on marketing and advertising and are by a huge amount the far the biggest funders of politicians and medical research of any lobbying group, so it may not be so strange that we do not hear

    from politicians or others
    or
    read much in the press about GS-441524
    or
    learn that the FDA coronavirus task force panel (declared in March 2020 via FDA filings) has 7 of the panel Drs who were very recently paid by Gilead - the Gilead connection is only declared if money has been received in the last 11 months
    or
    know that other panel members have ongoing or historic Gilead relationships (current adivisory Gilead panels etc) that did not need to be declared and that others on the panel wrote early papers supporting Remdesivir while holding key coronavirus panel or FDA positions

    https://www.covid19treatmentguidelines.nih.gov/panel-financial-disclosure/
    https://web.archive.org/web/20200421163941/https://www.covid19treatmentguidelines.nih.gov/panel-financial-disclosure/
    Reply
  • Valentine Michael Smith
    Chem721 said:
    ...Perhaps it was developed by combinatorial chemistry, assuming that is still alive and well.


    https://futurism.com/neoscope/injection-gene-edit-specific-parts-brain
    “The methods draw upon combinatorial chemistry used by the pharmaceutical industry for designing the drugs themselves, but instead we are applying the approach to designing the components of the delivery vehicle,” Xu added.
    Reply
  • adam
    It seems now very clear Gilead has had a deliberate long term strategy of blocking the development of its potentially more effective Coronavirus drug GS-441524 in favor of Remdesivir for profit reasons

    In 2019 Gilead confirmed to VIN News Service that it was blocking any development of the Coronavirus drug GS-441524 to protect Gileads interest in Remdesivir mainly because GS-441524 was the effective compound in Remdesivir

    Gilead has clearly continued to apply this blocking policy despite it being clear that GS-441524 was a potentially safer and more effective treatment for Covid-19 than Remdesivir and that GS-441524 was the main and active metabolite in Remdesivir for treating Covid-19, so would be more effective as an independent drug (but less profitable)

    There can be very little doubt based on the following Aug 2019 Gilead statements that commercial advantage has been the sole or main driver for Gilead blocking any parties researching GS-441524 as a Covid-19 treatment.


    From August 2019 VIN News Service see below



    A Gilead spokesperson told the VIN News Service that it is holding off on licensing GS-441524 to other parties for commercial development until remdesivir has FDA approval.

    A spokesperson for Gilead provided the following statement to VIN News:
    (Web link to VIN News info at end of this post)

    "Gilead in the past has worked to make compounds with the potential to help animals available to developers with the expertise to advance medicines for veterinary use. This is why we shared GS-441524 with UC Davis to research its impact on feline infectious peritonitis (FIP).

    "After we shared this compound with UC Davis, GS-441524 became an intermediate in the synthesis of remdesivir (GS-5734), which is under development for Ebola and other filoviruses. In addition, GS-441524 has been identified as a systemic metabolite of remdesivir in humans.

    "At this time, we are not providing GS-441524 to other parties until remdesivir has FDA approval. This is to avoid any interference with the regulatory process, which could risk the approval of remdesivir by the FDA to treat human patients with Ebola or other filoviruses.

    "We are, however, exploring options that would allow us to share GS-441524 before the FDA review is complete."

    Further background info on Gilead below with links to sources below

    https://forums.livescience.com/threads/could-cat-drugs-treat-humans-with-covid-19.3313/post-14671


    This inaction angers Gingrich, who is a Gilead shareholder. "Every single day nothing happens, cats are dying all over the world because of FIP," she said. In June, she sent a letter to Gilead chairman and CEO Daniel O'Day (with copies to her elected representatives and President Donald Trump) asking that the company do more to facilitate bringing GS to market.

    "With successful GS-441524 clinical trials, all the cat world thought this amazing cure would be on its way to the market," she wrote. "After all the work and collaboration, it was devastating to learn that UC Davis licensing of this game changing drug for use in cats would not be permitted by Gilead."

    Gingrich is referring to research by Dr. Niels Pedersen, whose clinical trials at UC Davis, School of Veterinary Medicine, identified GS as a safe and effective treatment for FIP.

    "Your company is being spoken about in a derogatory manner widely in the cat community right now," Gingrich continued in her letter. "As a stockholder, I don't like it, but do understand their feelings. They can't comprehend why Gilead will not help their cats and more cats from dying from FIP when it's within its power."

    Pedersen, too, expressed disappointment with Gilead's process.

    "We have learned the hard way that these human drug companies have no great interest in veterinary products and veterinary-based research," he wrote in email responses to questions from VIN News. "Even when we successfully proved that one of their drugs could cure FIP, we ultimately failed to convince them that they should allow animal rights on the discovery and to help directly or indirectly with getting FDA approval and ultimate licensing."



    https://news.vin.com/default.aspx?pid=210&Id=9235842&useobjecttypeid=10&fromVINNEWSASPX=1

    https://www.briafundsupporters.com/post/legal-treatment-for-fip-still-years-away-p2
    Reply