Chloroquine exerts direct antiviral effects, inhibiting phdependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Antimalarial effect of novel chloroquine derivatives as agents for the. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base and each 500. However, the mechanism of plasmodicidal action of chloroquine is not completely certain. Get a printable copy pdf file of the complete article 1. The precise mechanism by which chloroquine exhibits activity is not known.
Fox the antimalarial agents chloroquine and hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus. Although the mechanism of action is not fully understood, chloroquine is shown to inhibit the parasitic enzyme heme polymerase. Action of the toxic fpchloroquine and fp results in cell lysis and ultimately parasite cell autodigestion. Chloroquine is the drug of choice for travel to areas where chloroquine resistance has not been described. Among the four species of malarial parasite which infect humans. Here, we report ultrastructural changes associated with this phenomenon in cqresistant plasmodium chabaudi as strain after infected mice were administered cq and verapamil. In summary, there is no consensus that vacuolar ph change is the primary mechanism of action of chloroquine and other antimalarial quinolines.
Inhibition of dna replication is proposed as a general mechanism of the antimicrobial action of chloroquine. The drug chloroquine is bactericidal for bacillus megaterium. Chloroquine can inhibit a preentry step of the viral cycle by interfering with viral particles binding to their cellular cell surface receptor. Insights from nanomedicine into chloroquine efficacy. Chloroquine is an antimalaria medicine that works by interfering with the growth of parasites in the red blood cells of the human body. Inhibition of protein synthesis is also observed, evidently as a. In this study, we further investigated the mechanism of action of chloroquine, confirming that the drug prevents the maturation of gp120 at concentrations that are clinically relevant and achievable. Chq has, however, since accrued a plethora of uses in the treatment and. The past, present and future of antimalarial medicines. The effect of chloroquine dose and primaquine on plasmodium vivax recurrence. Chloroquine has been sporadically used in treating sarscov2 infection. Chloroquine binds to heme or fp to form the fpchloroquine complex. As the mechanism of action appears to be distinct from the mechanism of resistance, this identifies a vulnerable target for the development of new. The views expressed in documents by named authors are solely the responsibility of those authors.
It is a rapidly acting blood schizonticide, with some activity against gametocytes, but no activity against the hepatic stages of the malarial parasite. The mechanisms of action of hydroxychloroquine and chloroquine remain under continuous study in modern molecular medicine 17,18 using advanced tools in computational biology 19, synthetic biology. Except for its bitter taste, chloroquine is usually well tolerated and has a low incidence of serious. Parasites that cause malaria typically enter the body through the bite of a mosquito. Common side effects include vomiting, headache, changes in vision and muscle weakness. Malaria remains one of the leading causes of disease and death in the tropics, mainly of children under 5 years of age. In this video, i will explain into one of the main antimalarial drug, chloroquine. Ultrastructural changes associated with reversal of.
Mechanisms may include inhibition of viral enzymes or processes such as viral dna and rna polymerase, viral protein glycosylation, virus assembly, new. The theory of krogstad and colleagues relies on an additional nonweak base lysosomal accumulation of chloroquine of unknown form. Mechanism of action may be based on ability of chloroquine to bind and alter the properties of dna. Chloroquine resistant parasites accumulate less chloroquine in the food vacuole than do sensitive parasites fitch, 1970 and one assumption is that chloroquine resistance is not based on the mode of action of the drug but on the access of the drug to the parasite food vacuole.
Apart from the probable role of chloroquine on sarscov replication, the mechanisms of action of chloroquine on sarscov are not fully understood. Apart from its wellknown antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine is a member of the drug class 4aminoquinoline. Peters, w chemotherapy and drug resistance in malaria. In addition, the mechanism of action of nh 4 cl and chloroquine might depend on when they were added to the cells. It increases the ph of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. Once in the food vacuole, chloroquine is thought to inhibit the detoxification of heme. New insights on the antiviral effects of chloroquine. At parasitaemias of 57%, cq at 6 mgkg caused little morphological effect on. Chloroquine, a 4aminoquinoline, is an antiprotozoal agent. Chloroquine is a medication used to prevent and to treat malaria in areas where malaria is known to be sensitive. Chloroquine, may exert its effect against plasmodium species by concentrating in the acid vesicles of. While the drug can inhibit certain enzymes, its effect is believed to result, at least in part, from its interaction with dna. Structural and molecular modelling studies reveal a new.
Mechanisms of action of hydroxychloroquine and chloroquine. On 31 december 2019, who was informed of a cluster of cases of pneumonia of unknown cause detected in wuhan city, hubei province of china. Chloroquine resistance is associated with a decrease in the amount of chloroquine that accumulates in the food vacuole, the site of action for chloroquine. Susceptibility of human malaria parasites to chloroquine is ph dependent. Inhibition of protein synthesis is also observed, evidently as a secondary effect. It is caused by protozoan parasites belonging to the plasmodium genus and transmitted by an infected female anopheles mosquito. Facs analysis results can be found in the additional file 1. Produces a free radical when it undergoes an ironcatalyzed cleavage of an endoperoxide bond in the parasite food vacuole.
Antimalarial drug mechanism of action what is chloroquine. Chloroquine is a member of the drug class 4 aminoquinoline. Quinolinecontaining drugs such as chloroquine and quinine have had a long and successful history in antimalarial chemotherapy. Data were presented to indicate that the antimalarial drug chloroquine does not interfere with the normal antibody response in rabbits nor does it depress the l. Chloroquine is the most widely used drug against malaria, except for those cases caused by chloroquine resistant plasmodium falciparum. Mechanism of action of hydroxychloroquine as an antirheumatic drug by robert i. Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. Previous studies have suggested the elevation of ph as a mechanism by which chloroquine reduces the transduction of sarscov pseudotype viruses 17, 18. Chloroquine chq is a cheap, relatively well tolerated drug initially developed for the treatment of malaria in the 1930s. Pdf chloroquine is a prototype antimalarial drug, widely used in several branches of medicine. To further explore the detailed mechanism of action of cq and hcq in inhibiting virus entry, colocalization of virions with early endosomes ees or endolysosomes els was analyzed by.
Development of chloroquinecontaining hpma copolymers for. Common side effects include muscle problems, loss of appetite, diarrhea, and skin. Chloroquine, may exert its effect against plasmodium species by concentrating in the acid vesicles of the parasite and by inhibiting polymerization of heme. However, the mechanism of plasmodicidal action of chloroquine isget a printable copy pdf file of the complete article 1. Hydroxychloroquine, a less toxic derivative of chloroquine. Pdf for more than two decades, chloroquine cq was largely and deliberate used as first choice drug for malaria treatment.
Chloroquine is a potent inhibitor of sars coronavirus. On the mechanism of chloroquine resistance in plasmodium. Accumulation in food vacuole of the parasite role of ph gradient chloroquine trapping affects asexual cycle of plasmodium specie. The mechanism for this decreased accumulation is controversial. In vitro antiviral activity and projection of optimized. The coronavirus disease covid2019 was identified as the causative virus by chinese authorities on 7 january. Abstract development of chloroquine containing hpma copolymers for drug delivery fei yu, ph. It is believed to reach high concentrations in the vacuoles of the parasite, which, due to its alkaline nature, raises the internal ph. Effects of chloroquine on the feeding mechanism of the intraerythrocytic human malarial parasite plasmodium falciparum.
The effect of pyrimethamine and proguanil upon tissue hypnozoites and schizonts of. Polymers can be designed as either carriers of existing drugs or as polymeric drugs with intrinsic pharmacological activity. It rapidly enters and gets concentrated in food vacuole, present within erythrocytes. When added after the initiation of infection, these drugs might affect the endosomemediated fusion, subsequent virus replication, or assembly and release. This disease affects mainly children aged less than 5 years. Hydroxychloroquine, an alkylated 4aminoquinoline, is a hydroxylated form of chloroquine and has a biological mechanism of action similar to chloroquine s. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. Chloroquine phosphate is the phosphate salt of chloroquine, a quinoline compound with antimalarial and antiinflammatory properties. Hydroxychloroquine information for providers aidsinfo. Pdf efflux of chloroquine from plasmodium falciparum. Hydroxychloroquine was originally developed as a safer alternative to chloroquine for the treatment of malaria and was later found to have antirheumatic and antiinflammatory uses. Drug resistance in malaria world health organization. The recent emergence of the novel pathogenic sarscoronavirus 2 sarscov2 is responsible for a worldwide pandemic. Chloroquine also is taken up into the acidic food vacuoles of the parasite in the erythrocyte.
University of nebraska medical center, 2018 supervisor. Specifically it is used for chloroquine sensitive malaria. Mechanisms of action of antimalarial drugs springerlink. We have also demonstrated that chloroquine has broad antihiv activity, not only against laboratory strains from clade b but also against nonb. Synthetic polymers have been extensively explored for improved delivery of anticancer agents. Chloroquine accumulates in very high concentrations in the parasite food vacuole geary et al. Parasites that do not form hemozoin are therefore resistant to chloroquine. Recent multicentre clinical trials 1 and cell culture studies 2 suggest that the 70yearold malaria drug, chloroquine. Chloroquine has multiple mechanisms of action that may differ according to the pathogen studied. The use of chloroquine and hydroxychloroquine for noninfectious conditions other than rheumatoid arthritis or lupus. Chloroquine is a 4aminoquinolone compound with a complicated and still unclear mechanism of action. The ec50 values for chloroquine were greater than 100 microm at. The effect of chloroquine dose and primaquine on plasmodium. Two mechanisms are thought to be involved in chloroquine.
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