What is behind the smoke on Chloroquine ?
(yetenaweg)–First let’s see how the corona virus enters your cells ( See Image) .The virus enters the body through the nose, mouth or eyes, then attaches to cells in the airway that produce a protein called ACE2.
After attachment to the ACE2 receptors the virus is internalized in 2 ways – see Image below
1. Endosomal pathway – Chloroquine acts on this pathway
2. Cell Surface , non endosomal pathway
How Chloroquine an Old antiMalarial Became an Antiviral?
Chloroquine is used to prevent and treat malaria and is efficacious as an anti-inflammatory agent for the treatment of rheumatoid arthritis and lupus erythematosus. Studies revealed that it also has potential broad-spectrum antiviral activities by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV. 1
It acts at both entry level and post entry 2
- HydroxyChloroquine /Chloroquine interferes with the glycosylation of the ACE2 receptors which is a cellular pathway for coronaviruses 2
- It acts on the endosomal pathway – by alkalinization of Endosomes -the high pH environment inhibits endosomal proteases and therefore decreasing the cleavage of viral spike proteins – essentially blocking the virus from from opening up and releasing its genetic components 2
- Besides its antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo 2
Chloroquine is widely distributed in the whole body, including lung, after oral administration. 2
Probably because of its effect on the endosomal pathway , There is a strong rationality for the use of chloroquine to treat infections with intracellular microorganisms. i.e 3 malaria, Coxiella burnetii, treponema whipplei
What is the data on HydroxyChloroquine /Chloroquine on COVID 19 ?
Not a lot , but the few published have made it one of the few available drugs to treat COVID-19; lets see some of the studies done so far
* There was Evidence of Chloroquine effectiveness against (SARS)-associated coronavirus in Vitro 3, (2006 – The Lancet) , plus this study also showed the antiviral drug concentrations were not cytotoxic.
Following the in vitro results, 20 clinical studies were launched in several Chinese hospitals.
1st of which is described below
* The first results obtained from more than 100 patients showed the superiority of chloroquine compared with treatment of the control group in terms of reduction of exacerbation of pneumonia, duration of symptoms and delay of viral clearance, all in the absence of severe side effects . This has led in China to include chloroquine in the recommendations regarding the prevention and treatment of COVID-19 pneumonia 1
The subsequent in vivo data were communicated following the first results of clinical trials by Chinese teams and also aroused great enthusiasm among us. They showed that chloroquine could reduce the length of hospital stay and improve the evolution of COVID-19 pneumonia leading to recommend the administration of 500 mg of chloroquine twice a day in patients with mild, moderate and severe forms of COVID-19 pneumonia. 1, 4
The activity of hydroxychloroquine on viruses is probably the same as that of chloroquine since the mechanism of action of these two molecules is identical, and we are used to prescribe for long periods hydroxychloroquine, which would be therefore our first choice in the treatment of SARS-CoV-2. For optimal treatment, it may be necessary to administer a loading dose followed by a maintenance dose. 4
Most of this studies have small sample size , results are promising but are not validated yet with follow up studies and large sample size
There are multiple trials going on at this time on effectiveness of Hydroxychloroquine on COVID 19 ( on COVID 19 associated Severe Pulmonary infection, Mild COVID disease, Post exposure prophylaxis of SARS-COV2), please follow any updates on this trials on clinical trials.gov ( Use search word Hydroxychloroquine and COVID 19)
Follow national Guidelines and recommendations
Antibiotics that cure COVID-19 (last post was backwards)
እባካችሁን ቤት ውስጥ በመቀመጥ ህይወታችሁ አትርፍ በማለት እስፔሻል ዶክተሮች ህዝቡን መለመን ጀምረዋል። Please stay at home