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Antiviral drugs – antimalarials and anti HIV may be useful

Posted By Jo Nova On March 18, 2020 @ 4:58 pm In Global Warming | Comments Disabled

I’ve said from the start that anti-virals were always going to be more useful to us this year than vaccines, which take so long to test and be ready for use. What we really need are anti-virals which also happen to be preapproved and tested and hopefully in mass production. Chloroquine is cheap too, though I doubt Australian stocks of the drug are very high, or that our genius rulers have arranged more. This may be a godsend in Africa where chloroquine use is already high and may reduce the spread of Covid-19 somewhat.

The UK banned export of chloroquine a few weeks ago. Clearly someone there thought it might be useful.

Wang et al reported on Feb 4th that Chloroquine (anti-Malarial) and Remdesivir (anti HIV) may be useful against Coronavirus. They used lab experiments on cells in glass, which had promise. But “in vitro” doesn’t always mean “in vivo”. So I’ve been waiting for some results on people. Early reports were ambiguous. Recently this was hyped as an “Australian cure” which really just meant the start of a proper trial.

There are links to papers and discussion below but I can’t beat this great description explaining how inside the cells zinc stops a major viral protein from copying the virus. Chloroquine is a zinc ionophore — it opens the ion gates and pumps zinc into the cell, just what we want if we have virus trying to take over the cellular machinery.

The South Korean results are not based on a randomized blind trial so we can’t be sure if it works. But the South Korean death rates are lower. Perhaps they are doing a better treatment than Italy. Perhaps the viral strains are different. Perhaps the population is different, older, have higher blood pressure, etc etc.

Japan is trailling HIV meds. 

h/t to Bulldust, Geoff S, Willie Soon, Eric Worrall, David E, Hugh P, Colin A, Chris D.

Please send a letter to incompetent Health Ministers to make sure they are looking at how to maximize stocks now, and to remove bureaucratic hurdles to using this for the most severe cases, which may help reduce the ICU load as well as keep people alive.

This is yet another reason to go hard, go fast, reduce the rate of infections.

If treatments are just around the corner, the financial and “lives” advantage will be amplified if we stop the explosive exponential curve as fast as possible. Brendan-let-them-die-Murphy our fatalistic Chief Medical Officer seems to have given up on saving as many Australians as possible.

New Chloroquine study in France

A renowned research professor in France has reported successful results from a new treatment for Covid-19, with early tests suggesting it can stop the virus from being contagious in just six days.

Professor Didier Raoult from infection hospital l’Institut Hospitalo-Universitaire (IHU) Méditerranée Infection in Marseille (Bouches-du-Rhône, Provence-Alpes-Côte d’Azur), published a video explaining the trials on Monday March 16.

This was a small study on only 24 patients. Doses were 600mcg/day for ten days.

“We were able to ascertain that patients who had not received Plaquenil (the drug containing hydroxychloroquine) were still contagious after six days, but of those that had received Plaquenil, after six days, only 25% were still contagious.”

On March 13 another paper wrote up the guidelines from South Korean doctors and Chinese medical teams.

Treatment Guidelines from South Korea[7]

  1. If patients are young, healthy, and have mild symptoms without underlying conditions, doctors can observe them without antiviral treatment;
  2. If more than 10 days have passed since the onset of the illness and the symptoms are mild, physicians do  not have to start an antiviral medication;
  3. However, if patients are old or have underlying conditions with serious symptoms, physicians should  consider an antiviral treatment. If they decide to use the antiviral therapy, they should start the administration as soon as possible: … chloroquine 500mg orally per day.
  4. As chloroquine is not available in Korea, doctors could consider hydroxychloroquine 400mg orally per day (Hydroxychloroquine is an analog of chloroquine used against malaria, autoimmune disorders, etc.  It is widely available as well).
  5. The treatment is suitable for 7 – 10 days, which can be shortened or extended depending on clinical progress. Notably, the guidelines mention other antivirals as further lines of defense, including anti-HIV drugs.

Mechanism of action — increases intracellular pH to clogs up cells machinery which stops viral replication.

A different view on how it works (I prefer the video description above).

 COVID-19 in a single stranded, positive strain RNA virus with a protein shell and membrane.  The genome is of the same sense of the mRNA.  It goes through a lifecycle where incoming viral COVID genome has to become double stranded RNA and the new strand becomes the new strand for the new mRNA.  There are significant similarities between COVID-19 and SARS coronavirus.  Both COVID-19 and SARS-like coronaviruses have machinery for regulating their own replication and production of their proteins.  Coronavirus depends on the breakdown of macromolecules such as proteins.  Specifically, the virus depends on turning over the host proteins to trigger response for available building blocks to make their own proteins or nucleic acids.  They break down due to low PH catalyzed by hydrolysis. Additionally, coronaviruses have non-structural proteins that are not part of the capsid (protein shell of the virus).  These non-structural proteins are regulatory proteins that take over the host cell and suppress the immune system of the host (similar to HIV).  Coronavirus can create growth factor like mechanisms (e.g. cytokines) to optimize the growth environment in the cell to favor it.

 It is this part of the coronavirus’ replicative path that chloroquine inhibits.  Notably, because of its nitrogen structure, chloroquine has the unique ability to get into cells and cross endosomal membranes.  Once inside, nitrogens in chloroquine (and quinines in general) prevent acidification by absorbing a high amount of hydrogens that simply then interact with nitrogen and then chloroquine becomes positively charged – an ionic interaction which makes it harder for the endosome to become acidified.  The result is a buffer that holds it at the higher pH and prevents it from becoming acidic enough to be functional.  To summarize, because chloroquine has a multitude of extra nitrogens, once it crosses the membrane and enters an organelle, the organelle is prevented from reaching a lower pH.  The organelle’s enzymes cannot work because the donor group will be a hydrogen ion, disabling the hydrolysis required for coronavirus replication.  This means that all kinds of events in the cell are incapable of performing optimally, including viral replication.

 Chloroquine’s entrance into the organelle likely constipates the whole system.  An analogy is that the virus is like a garbage facility which has to break down and burn up the garbage and if it cannot, the garbage piles up and the city becomes paralyzed.  This is likely the case for any virus, cancer cells or any other condition that is dependent on turning over the worn out or incorrectly synthesized proteins.

In this view it’s a broadscale clogger of cellular machinery and you probably wouldn’t want to take it every day, but in an extreme situation it could be very helpful in buying time.

Other FDA approved drugs might help too:

 As per Steve Schow PhD, Professor of Chemical and Systems Biology at Stanford University School of Medicine and Lead Advisor to Stanford’s SPARK Translational Research Program:

 “There are a number of related isoquinoline and quinoline drug family members who might exhibit the same general acid neutralizing effects. In addition certain antidepressants and antipsychotic drugs are known to accumulate in lysosomes via this acid-base process and might be effective here if the doses needed aren’t too high.”[18]

There are always side-effects

Worth knowing: Low dose long term use raised all cause death rates by 25%. Hm.

Quinine for leg cramps increases risk of death, study finds

 Last year, the U.S. Food and Drug Administration warned against using quinine as an antidote for night-time leg muscle cramps or “restless legs,” said Patel. The FDA reported “adverse events with serious outcomes … including 93 deaths” in people who used the remedy. And it wasn’t the first time health officials have expressed concerns about quinine. The substance is linked to bleeding and an irregular heart rate. Quinine is only FDA-approved for use as a malaria treatment.

They analyzed data on individuals who had taken 100 milligrams of quinine salt per day or more, and who had used the pills for at least one year between January 1990 and December 2014, and compared them to a larger group of patients who had not used quinine. The follow-up period was about 5.7 years.

Death rates among quinine-takers were higher over time. There were 11,598 deaths (4.2 per 100 person-years) among the 44,699 participants who took quinine compared with 26,753 deaths (3.2 per 100 person-years) among the 130,496 people who didn’t take the pills.

Note the doses: the leg cramp study people were taking the equivalent of more than 1L of Tonic a day.

The FDA only allows 83 milligrams of quinine per liter bottle of tonic or quinine water. That comes out to be about 20 milligrams of quinine per 8-ounce glass.

It’s not clear to me what does of Tonic Water would even be applicable. The South Koreans were talking about 400-500mg which is 5L of tonic water a day (assuming that quinine = chloroquinone = Hydroxychloroquine which is not true).

For those wondering why vaccines are so slow — it’s because there is really no shortcut to the three stage process of testing a new drug. Phase I is low dose just to make sure the drug doesn’t obviously hurt people. Possible downsides to vaccines include that sometimes, rarely, the disease can even be worse in people infected after being vaccinated. Biggest problem is that it may not provoke a useful response from the immune system or it may work, but not last long, and it may takes months of work to find that kind of thing out.

______________________________________________

Coronavirus Background: ☀ The Demographics: the severity increases with age, and slightly more for men than women. ☀ The Ro is 2 – 3 and exponential curves are steep. How Coronavirus kills: why the number of ICU units matters so much. ☀ Illness progression: Dry coughs and Fevers, Aches. In 15% of people, by day 5 breathing trouble starts. In 3% (?) by day 8 they may need an ICU (intensive care unit). ☀ The good case of Singapore but the ominous calculations of how fast the ICU beds may run out. ☀ Proof that viruses don’t have wings and we should have stopped all flights so much earlier. ☀ The story of how American Samoa avoided Flu Deaths with quarantine in 1918. ☀ The story of Vo, the Italian town that stopped the virus. ☀ Delay = Death, statistics show mortality rates rise tenfold if hospitals are overwhelmed. ☀ Projections of all US States death tolls depending on quarantine levels and the date that hospitals could be overwhelmed ☀ One doctor describes his “Holy S***” moment ☀ ☀ ☀

We must Crush the Curve to save lives and the economy.

Economics: ☀ The huge impact on the Chinese economy ☀ the awful case of Iran.☀

Beware UN advice:Ethiopian WHO chief was part of China’s debt trap diplomacy ☀

Stats and Data: John Hopkins Live Map Worldometer Coronavirus data in Australia

 

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