Forwarded from Ehden's Channel
#MERCKyBusiness - disproved² thread
In this part I will address the claims that Merck has already addressed the genotoxicity concerns, because obviously, the minute you make a claim against #BigPharma you are assured to get "fact checkers" demanding to cancel you.
The whole saga started with a research I've mentioned its results above, entitled "β-D-N 4-hydroxycytidine (NHC) inhibits SARS-CoV-2 through lethal mutagenesis but is also mutagenic to mammalian cells.".
Zhou et al claimed that "rNHC (or molnupiravir) Is Mutagenic in a Mammalian Cell Assay" and that "there are risks for the host in that the same mutagenic activity that impacts viral replication has the potential for incorporation and mutagenesis of host DNA."
They also stated that "mutations in host DNA COULD CONTRIBUTE TO THE DEVELOPMENT OF CANCER, , OR CAUSE BIRTH DEFECTS EITHER IN A DEVELOPING FETUS OR THROUGH INCORPORATION INTO SPERM PRECURSOR CELLS".
What was even more worrying is that a short therapy would not prevent the host from exposure "because both RNA precursors that affect the virus and DNA precursors that would affect the host pass through the common ribonucleoside diphosphate intermediate."
This started disproved² saga. Let us look at "Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19" ("Current Opinion in Virology", Oct 2021)
This article (AFAIU) is an editorial by the researchers who developed/worked on molnupiravir, telling the story of their work. It is useful to start with it, even though it is retrospective, as it gives good context.
First, the predecessor of molnupiravir (EIDD-2801) was EIDD-1931, which has the capacity to cross the blood–brain barrier, as it was developed to treat VEEV (Venezuelan equine encephalitis virus).
AFAIU, It means molnupiravir can cross the brain barrier.
"EIDD-1931 was orally bioavailable, widely distributed to organs including the lungs and appeared to be actively transported into the CNS where it was quickly anabolized to the active 5'-triphosphate"
EIDD-1931 inhibits replication of multiple RNA viruses of influenza, various coronaviruses, respiratory syncytial virus (RSV), VEEV), Chikungunya and Ebola (in animal models). HOWEVER, it metabolized quickly in non-human primates.
EIDD-2801 (molnupiravir) is a prodrug of EIDD-1931, which "facilitated movement across the gut lining and EFFICIENTLY DELIVERED EIDD-1931 to the circulating volume of all species tested, including non-human primates"
*BREAK*
Notice - molnupiravir is in fact a drug that was designed to deliver EIDD-1931 in an efficient way.
Now comes the interested section - the genotoxicity tests:
"Because of a positive Ames test, the potential for genotoxicity has been thoroughly evaluated for molnupiravir both in vitro and in vivo."
Ames test use a bacteria to test if a given chemical can cause mutations in the DNA of an organism being tested.
(JUST A REMINDR)
In vitro ("in the glass" in Latin) - test performed on living tissue.
In vivo ("in the living" in Latin) - test on an organism, such as a rodent, or human beings.
According to the article, they performed two in vivo rodent mutagenicity assays: the Pig-a mutagenicity assay, and the Big Blue1 (cII Locus) transgenic rodent assay.
MERCKyBusiness.
According to the authors, "in both assays…the impact of molnupiravir treatment on mutation rates was not differentiable from mutation rates observed in untreated historical control animals."
Even better, "molnupiravir was negative for induction of chromosomal damage in in vitro micronucleus (with and without metabolic activation) and in vivo rat micronucleus assays."
Which led the authors to conclude "based on the totality of genotoxicity data molnupiravir is not considered to pose an increased risk of genotoxicity in clinical use."
Problem solved, right?
Not so quick.
Let's dig in a little bit.
In this part I will address the claims that Merck has already addressed the genotoxicity concerns, because obviously, the minute you make a claim against #BigPharma you are assured to get "fact checkers" demanding to cancel you.
The whole saga started with a research I've mentioned its results above, entitled "β-D-N 4-hydroxycytidine (NHC) inhibits SARS-CoV-2 through lethal mutagenesis but is also mutagenic to mammalian cells.".
Zhou et al claimed that "rNHC (or molnupiravir) Is Mutagenic in a Mammalian Cell Assay" and that "there are risks for the host in that the same mutagenic activity that impacts viral replication has the potential for incorporation and mutagenesis of host DNA."
They also stated that "mutations in host DNA COULD CONTRIBUTE TO THE DEVELOPMENT OF CANCER, , OR CAUSE BIRTH DEFECTS EITHER IN A DEVELOPING FETUS OR THROUGH INCORPORATION INTO SPERM PRECURSOR CELLS".
What was even more worrying is that a short therapy would not prevent the host from exposure "because both RNA precursors that affect the virus and DNA precursors that would affect the host pass through the common ribonucleoside diphosphate intermediate."
This started disproved² saga. Let us look at "Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19" ("Current Opinion in Virology", Oct 2021)
This article (AFAIU) is an editorial by the researchers who developed/worked on molnupiravir, telling the story of their work. It is useful to start with it, even though it is retrospective, as it gives good context.
First, the predecessor of molnupiravir (EIDD-2801) was EIDD-1931, which has the capacity to cross the blood–brain barrier, as it was developed to treat VEEV (Venezuelan equine encephalitis virus).
AFAIU, It means molnupiravir can cross the brain barrier.
"EIDD-1931 was orally bioavailable, widely distributed to organs including the lungs and appeared to be actively transported into the CNS where it was quickly anabolized to the active 5'-triphosphate"
EIDD-1931 inhibits replication of multiple RNA viruses of influenza, various coronaviruses, respiratory syncytial virus (RSV), VEEV), Chikungunya and Ebola (in animal models). HOWEVER, it metabolized quickly in non-human primates.
EIDD-2801 (molnupiravir) is a prodrug of EIDD-1931, which "facilitated movement across the gut lining and EFFICIENTLY DELIVERED EIDD-1931 to the circulating volume of all species tested, including non-human primates"
*BREAK*
Notice - molnupiravir is in fact a drug that was designed to deliver EIDD-1931 in an efficient way.
Now comes the interested section - the genotoxicity tests:
"Because of a positive Ames test, the potential for genotoxicity has been thoroughly evaluated for molnupiravir both in vitro and in vivo."
Ames test use a bacteria to test if a given chemical can cause mutations in the DNA of an organism being tested.
(JUST A REMINDR)
In vitro ("in the glass" in Latin) - test performed on living tissue.
In vivo ("in the living" in Latin) - test on an organism, such as a rodent, or human beings.
According to the article, they performed two in vivo rodent mutagenicity assays: the Pig-a mutagenicity assay, and the Big Blue1 (cII Locus) transgenic rodent assay.
MERCKyBusiness.
According to the authors, "in both assays…the impact of molnupiravir treatment on mutation rates was not differentiable from mutation rates observed in untreated historical control animals."
Even better, "molnupiravir was negative for induction of chromosomal damage in in vitro micronucleus (with and without metabolic activation) and in vivo rat micronucleus assays."
Which led the authors to conclude "based on the totality of genotoxicity data molnupiravir is not considered to pose an increased risk of genotoxicity in clinical use."
Problem solved, right?
Not so quick.
Let's dig in a little bit.
Forwarded from Ehden's Channel
IN OUR UPCOMING SECTION, I will look at a more detailed of the actual tests, ask if it was really disproved, and … well, perhaps even reach the disproved² phase.
#MERCKyBusiness
https://twitter.com/eh_den/status/1444453938007363587
https://threadreaderapp.com/thread/1443971976586989570?refresh=1633219718
#MERCKyBusiness
https://twitter.com/eh_den/status/1444453938007363587
https://threadreaderapp.com/thread/1443971976586989570?refresh=1633219718
Twitter
Ehden @ TELEGRAM CHANNEL: T.ME/EH_DEN
#MERCKyBusiness - disproved² thread 1/x In this part I will address the claims that Merck has already addressed the genotoxicity concerns, because obviously, the minute you make a claim against #BigPharma you are assured to get "fact checkers" demanding to…
Forwarded from HealthImpactNews
Killer COVID Vaccines: 4,400% Increase in Deaths Compared to All FDA-Approved Vaccines for Previous 30 Years
#covidvaccineskill #RealNotRare #plandemic #covidbioweaponshots #bigpharma
https://healthimpactnews.com/2022/killer-covid-vaccines-4400-increase-in-deaths-compared-to-all-fda-approved-vaccines-for-previous-30-years/
#covidvaccineskill #RealNotRare #plandemic #covidbioweaponshots #bigpharma
https://healthimpactnews.com/2022/killer-covid-vaccines-4400-increase-in-deaths-compared-to-all-fda-approved-vaccines-for-previous-30-years/