Lysosomes ph and the antimalarial action of chloroquine

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  1. hijack23 Guest

    Lysosomes ph and the antimalarial action of chloroquine


    For decades, the drug was a front-line treatment and prophylactic for malaria. In a three-page paper published Tuesday in Cell Research, scientists at the Wuhan Institute of Virology’s State Key Laboratory of Virology write that both chloroquine and the antiviral remdesivir were, individually, “highly effective” at inhibiting replication of the novel coronavirus in cell culture.

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    Chloroquine and ammonium chloride, by virtue of their basic properties, have been shown to raise endocytic and lysosomal pH and thereby interfere with normal iron metabolism in a variety of cell types, including mononuclear phagocytes. Cellular iron metabolism is of critical importance to Legionella pneumophila. Krogstad DJ, Schlesinger PH. The basis of antimalarial action non-weak base effects of chloroquine on acid vesicle pH. Am J Trop Med Hyg. 1987 Mar; 36 2213–220. Krogstad DJ, Schlesinger PH. Acid-vesicle function, intracellular pathogens, and the action of chloroquine against Plasmodium falciparum. N Engl J Med. 1987 Aug 27; 317 9542–549. Chloroquine mechanism of drug action and resistance in Plasmodium falciparum. Slater AF1. Author information 1Picower Institute for Medical Research, Manhasset, NY 11030. Quinoline-containing drugs such as chloroquine and quinine have had a long and successful history in antimalarial chemotherapy.

    “It’s interesting in that it really lacks a lot of details but, nevertheless, if you look at the data as presented, at least in vitro, it seems like chloroquine can be used as an early-stage drug,” he said. Their drug screen evaluated five other drugs that were not effective. Though the paper is brief, John Lednicky, a professor at the University of Florida’s Emerging Pathogens Institute, found its results intriguing.

    Lysosomes ph and the antimalarial action of chloroquine

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  5. Chloroquine raises the pH in host-cell lysosomes, which interferes with viruses’ attempts to acidify the lysosomes, a prerequisite to formation of the autophagosomes that cells use to eat themselves. In the Cell Research paper, the researchers found that the drug was effective at inhibiting the virus as it was both entering and exiting cells.

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    Chloroquine analog is a diprotic weak base. The unprotonated form of chloroquine diffuses spontaneously and rapidly across the membranes of cells and organelles to acidic cytoplasmic vesicles such as endosomes, lysosomes, or Golgi vesicles and thereby increases their pH Al‐Bari 2015. Chloroquine accumulates preferentially in lysosomes and raises intralysosomal pH, which in turn increases the permeability and volume of lysosomes. The increased intralysosomal pH produced by chloroquine analogues may not be sufficient to cause cellular damage specifically in tumour cells at therapeutically achievable concentrations. Oct 01, 2018 C 18 H 26 ClN 3.2H 3 PO 4 Molecular Weight 515.87 Each tablet contains 500 mg of Chloroquine phosphate USP, equivalent to 300 mg Chloroquine base. Inactive Ingredients colloidal silicon dioxide, dibasic calcium phosphate, hydroxypropylmethylcellulose, magnesium stearate.

     
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  7. 223344 New Member

    Hydroxychloroquine is a quinoline medicine used to treat or prevent malaria, a disease caused by parasites that enter the body through the bite of a mosquito. Hydroxychloroquine Uses, Dosage & Side Effects - Plaquenil Uses, Dosage & Side Effects - Plaquenil Oral Uses, Side Effects, Interactions, Pictures.
     
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