Anti Malaria Drug Fights Corona Virus Covid-19

Joined
Aug 21, 2018
Messages
1,237
I tried to understand mechanism of action, my limited knowledge didn't allow me. There is a study of chloroquine and hydroxychloroquine effects on redox balance. I didn't understand it. What makes me believe it's somehow related is that methylene blue is know for it's ability to alter redox and MB is antimalarial too.
 

Jam

Member
Joined
Aug 10, 2018
Messages
2,212
Age
52
Location
Piedmont
Are Chloroquine and Hydroxychloroquine Zinc Ionophores? [COVID-19 Updates]
by Chris Masterjohn

The best chance for inhibiting viral replication, then, lies in increasing cytosolic zinc, not endosomal zinc.

But chloroquine doesn't increase cytosolic zinc. It traps zinc in lysosomes, where it is irrelevant to viral replication.

So how does chloroquine kill SARS-CoV and SARS-CoV-2 in vitro? Here's what those in vitro papers found:

  • It increases endosomal pH. Fusion of the virus with the endosome, and later escape of the virus from the endosome, can both be pH-dependent. Increasing endosomal pH appears to prevent fusion of SARS-CoV with the endosome, and to the extent it makes it in, might also prevent its escape into the cytosol. This is supported by the fact that ammonium chloride, another agent that increases endosomal pH, has the same effect.
  • Chloroquine and ammonium chloride also raise the pH in the golgi apparatus, the compartment where sugars are added to proteins in a process known as glycosylation. ACE2, the protein on the cell surface that allows the entry of SARS-CoV and SARS-CoV-2 into the cell, is one of the proteins that are glycosylated in the golgi. Chloroquine and ammonium chloride both interrupt the glycosylation of ACE2. They do not affect the amount of ACE2 on the cell surface, but it is possible that the the virus is less able to dock to ACE2 when the protein hasn't been glycosylated.
Chloroquine raises the pH of the endosomes, lysosomes, and golgi. This is a clearly toxic effect of the drug on human cells, because it will broadly disrupt the ability of the cell to take in things from its environment, digest things that need to be broken down, and glycosylate things that need to be glycosylated. As a result, chloroquine also interferes with the glycosylation of antibodies, which most likely contributes to its ability to treat autoimmune conditions. However, it might also hurt the immune defense against viruses, which might underly why it acted as an antiviral against chikungunya virus in vitro but enhanced viral replication in vivo.

As noted yesterday, despite the routine use of chloroquine against COVID-19 in China and its incorporation into at least two national guidelines for COVID-19, there is as yet no evidence it is effective.

In any case, what, if anything does this say about quercetin? I'll let you know tomorrow.
 

Similar threads

Back
Top Bottom