key: cord-0996418-9q3lmsd3 authors: Colson, Philippe; Rolain, Jean-Marc; Lagier, Jean-Christophe; Brouqui, Philippe; Raoult, Didier title: Chloroquine and hydroxychloroquine as available weapons to fight COVID-19 date: 2020-03-04 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2020.105932 sha: 442e3ade0116f30020d3fda17e6c060e73cf3cdb doc_id: 996418 cord_uid: 9q3lmsd3 nan Repositioning of drugs for use as antiviral treatments is a critical need [1] . It is commonly very badly perceived by virologists, as we experienced when reporting the effectiveness of azithromycin for Zika virus [2] . A response has come from China to the respiratory disease caused by the new coronavirus (SARS-CoV-2) that emerged in December 2019 in this country. Indeed, following the very recent publication of results showing the in vitro activity of chloroquine against SARS-CoV-2 [3] , data have been reported on the efficacy of this drug in patients with SARS-CoV-2-related pneumonia (named COVID-19) at different levels of severity [4 , 5] . Thus, following the in vitro results, 20 clinical studies were launched in several Chinese hospitals. 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 [4 , 5] . This has led in China to include chloroquine in the recommendations regarding the prevention and treatment of COVID-19 pneumonia [4 , 6] . There is a strong rationality for the use of chloroquine to treat infections with intracellular micro-organisms. Thus, malaria has been treated for several decades with this molecule [7] . In addition, our team has used hydroxychloroquine for the first time for intracellular bacterial infections since 30 years to treat the intracellular bacterium Coxiella burnetii , the agent of Q fever, for which we have shown in vitro and then in patients that this compound is the only one efficient for killing these intracellular pathogens [8 , 9] . Since then, we have also shown the activity of hydroxychloroquine on Tropheryma whipplei , the agent of Whipple's disease, which is another intracellular bacterium for which hydroxychloroquine has become a reference drug [10 , 11] . Altogether, one of us (DR) has treated ~40 0 0 cases of C. burnetii or T. whipplei infections over 30 years (personal data). Regarding viruses, for reasons probably partly identical involving alkalinisation by chloroquine of the phagolysosome, several studies have shown the effectiveness of this molecule, including against coronaviruses among which is the severe acute respiratory syndrome (SARS)-associated coronavirus [1 , 12 , 13] ( Table 1 ) . We previously emphasised interest in chloroquine for the treatment of viral infections in this journal [1] , predicting its use in viral infections lacking drugs. Following the discovery in China of the in vitro activity of chloroquine against SARS-CoV-2, discovered during culture tests on Vero E6 cells with 50% and 90% effective concentrations (EC 50 and EC 90 values) of 1.13 μM and 6.90 μM, respectively (antiviral activity being observed when addition of this drug was carried out before or after viral infection of the cells) [3] , we awaited with great interest the clinical data [14] . The subsequent in vivo data were communicated following the first results of clinical trials by Chinese teams [4] 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 [4 , 6] , 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. At such a dosage, a therapeutic concentration of chloroquine might be reached. With our experience on 20 0 0 dosages of hydroxychloroquine during the past 5 years in patients with long-term treatment ( > 1 year), we know that with a dosage of 600 mg/day we reach a concentration of 1 μg/mL [15] . The optimal dosage for SARS-CoV-2 is an issue that will need to be assessed in the coming days. For us, 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. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century Azithromycin inhibits the replication of Zika virus Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies ? title=%E6%B0%AF%E5%96%B9&officialname=&subjectid=&secondaryid= &applier=&studyleader=ðicalcommitteesanction=&sponsor=&studyailment= &studyailmentcode=&studytype=0&studystage=0&studydesign= 0&minstudyexecutetime=&maxstudyexecutetime=&recruitmentstatus= 0&gender=0&agreetosign=&secsponsor=®no=®status=0&country= &province=&city=&institution=&institutionlevel=&measure=&intercode= &sourceofspends=&createyear=0&isuploadrf=&whetherpublic=&btngo= btn&verifycode=&page=1 Multicenter Collaboration Group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for Chloroquine in the Treatment of Novel Coronavirus Pneumonia Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells Whipple's disease In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine New insights into the antiviral effects of chloroquine Chloroquine for the 2019 novel coronavirus SARS-CoV-2 Treatment of classic Whipple's disease: from in vitro results to clinical outcome Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. 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