If so, I had a similar experience, but never made it to elemental analysis since the molecule had other problems. Hell of a protein… built a lot of character. The coronavirus is yet another example that no one in the biological or chemical sciences has a clue what they are doing….. Hopefully this will wake everyone up to the fact that everyone in their field can spend their whole career as a top scientist and literally be cranking out useless academic junk.
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Fair point. Although to be fair the virus has only functionally existed for a few short months we assume. As a chemist done time on the receiving end of cell biology, seems to me that even if biochemistry an order of magnitude or two less fuzzy, still be no mean feat to come up with a therapy in shining armour that could rescue us fast enough. Always great fun pricking over inflated balloons.
Thanks for that. Fired off to printer and set upon with with highlighter pen. Hard going for old buffer unsteeped in antivirals. Thrust is that a the? As stated on p , para Plenty to ponder. Thank you highlighter with the green and yellow pens. As concluded on p The possibility of the reemergence of SARS and other novel viruses from animals or laboratories and therefore the need for preparedness should not be ignored. Scientific findings do not automatically trickle upwards to the powers that be. What efforts were made to make these findings known to authorities?
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Chloroquine played important part in the MedChem history. It was also at the beginning of the discovery of quinolone class of antibacterials. During antibacterial screening at Sterling, they screened also some impurities from their chloroquine production and found one of them, 7-chloroethyloxo-1,4-dihydroquinolinecarboxylic acid, active against G - strains.
Modification of the structure led to nalidixic acid, the first drug of the class. It has been shown that alteration of N-linked glycans of ACE2 does impair the CoV envelope spike glycoprotein-triggered membrane fusion. If chloroquine would be effective by disturbing the biosynthesis of N-glycans e. Indeed numerous derivatives of 1-deoxynojirimycin and castanospermine iminosugars from e. N-butyldeoxynojirimycin Miglustat is an existing drug that reduces the above mentioned fusion in models, but other derivatives are more potent.
Antimicrob Agents Chemother , — But it does have such effects in a percentage of the population. My thinking is that if tens of millions of people try to take it prophylactically, we could see some trouble. Is enough known to write a story on how chloroquine metabolizes differently for people with cytochrome polymorphisms?
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Nice paper. The EC50s against highly pathogenic CoVs similar. Time of addition favors CQ use as primary prevention only see Vincent et al, Virology Journal , As of today, infected frontline healthcare professionals in Italy are infected. Daily administration mg hydroxyCQ should block infectivity. At least the theory is nice. For those of us who took a lot of chloroquin in the old days to ward off malaria—I spent two years in the African bush in the mids—the thought that it might make a comeback brings mixed emotions. I caught malaria anyway, and the impact of the drug on everything from eyesight to liver function was hotly debated.
Presumably, the medical and pharmaceutical professions have a lot better understanding of side effects of the drug today. There are mitochondrial benefits and it delays aging. Also it works with light so if you take it and go out in the sunlight it can work even better. Do you for sure know that it cant do the same thing as the pharmaceutical malaria drug.
From what I understand that hydroquinine performs two functions. Increase non permeability of the cell wall making it a it more acidic and the virus proteins have less ability to cleave and also deactivation of the receptor sites as well. Do we know that MB does not do the same thing. I am not advocating it I just used it for bio hacking the mitochondria and knew it was better at treating malaria then the hydroquinine at least that is what a study suggested.
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From what I understand that hydroxychloroquine performs two functions. I am not advocating it I just used it for bio hacking the mitochondria and knew it was better at treating malaria then the hydroxychloroquine at least that is what a study suggested. Pretty widely used drug, and as several have noted, relatively benign. For short-term antiviral treatment, perhaps the possibility of QT prolongation is most concerning. We need to stop being trapped by the paradox of expertise and waiting for the gold standard proofs of controlled trials.
Crisis calls for breaking rules and innovating. Treatments already approved for other conditions should be applied widely now, and proofs can wait til later. I have great respect for our medical professionals, but this is not a time for the typical level of caution that they have all grown up in. This is a classic example of the a paradox of expertise. The existing rules regarding the use of these drugs evolved because people have been injured by them.
The paradox of expertise can be resolved to one question: who gets to be the experimental animal in which the effectiveness of chloroquine or hydroxychloroquine in treatment of COVID are measured? Maybe some family in China or India?
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Interesting to see that a study was initiated on 6th February…. Example include influenza Lancet Infect Dis. Intracellular zinc was shown to inhibit the production of the viral replicase polypeptide. Viral replicase is what is read by the host cell to produce the virions that are the cause of the continuing infection of the human host.
This is where chloroquin shines because it, as acts as a zinc ionophore opening up a zinc ion transport channel through which extracellular zinc can then pass through via diffusion. Once inside the cell space zinc can then act to inhibit replicase transcription and stop the formation of the replicase which in turn suppresses the production of the proteins that make up the virions.
Less virions allows are immune system to attack the invading viruses and the few virions produced thus decreasing the severity and duration of the illness.
My questions are whether or not quinine itself is a zinc ionophore , what other substances are zinc ionophores and would the use of Micellular Zinc which is zinc coated in a lipid compound usually stearic acid or stearate be as effective as using chloroquin to transport extracellular zinc into the intracellular space? What do we think about this article in Bloomberg News? The implication is that chloroquine is deadly in commonly prescribed doses.
Chloroquine may or may not be a safe prophylactic medication over a period of weeks, but the choice facing many is a sure death once COVID takes hold in an elderly or immunosuppressed person versus the chance of suffering toxic side effects if chloroquine and azithromycin prove to be effective against the infection. Bloomberg is playing P. Super interesting article. By which date, do you expect the scientific community to know if this could or not be a highly efficient solution against CV19? There are millions? Surely there must be enough data collected by now to see if there is any prophylactic or treatment effects?
Did you get an answer on this? I just returned from the East and have this med Atovaqoune and proguanil on hand. Govt of India is recommending Hydroxy chloroquine for prophylaxis of SARS-CoV-2 infection for following: 1 asymptomatic healthcare providers involved in care of suspected or confirmed cases of Covid Dosage mg twice a day on day 1 mg once a day for next 7 weeks 2 asymptomatic household contacts of confirmed cases Dosagemg twice a day in day 1 mg once a day for next 3 weeks Standard precautions to be taken with meals and side effects mentioned.
Would you think mefloquine would have the same beneficial effects as chloroquine regarding coronovirus? I took mefloquine as an anti-malarial for many years with no ill effects. Interesting blog! I fear these numbers could be artifacts of low rates of testing. And, now, a death from people self medicating. A couple in Arizona took chloroquine phosphate that they had for their aquarium, to treat fish. Husband died pretty quickly and the wife is very ill.
Lynn, Arizona chloroquine death: Does anyone know if aquarium chloroquine phosphate has additional ingredients not found in human medical chloroquine?
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Or was this a huge overdose problem? Depending on the size, there should be at least 1 gram in there. Just out of curiosity about the supposed harmlessness of chloroquine. Reaching for reasons this obscure to criticize someone induces a kind of Streisand effect in the audience.