PMC:7102591 / 21223-23181 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7102591","sourcedb":"PMC","sourceid":"7102591","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7102591","text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection 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