key: cord-0991302-cpu3q9o6 authors: Sahraei, Zahra; Shabani, Minoosh; Shokouhi, Shervin; Saffaei, Ali title: Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine date: 2020-03-17 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2020.105945 sha: c46981d79358841d13230dee08d5ecc6cca84c77 doc_id: 991302 cord_uid: cpu3q9o6 nan Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread rapidly across China. As of 7 March 2020, the infection was reported from 97 countries globally. To date, 103 882 patients have been confirmed to have COVID-19, of whom 3522 have died [1] . Recently, many trials have been designed to determine an effective therapeutic regimen for COVID-19. Of the target regimens, chloroquine therapy is being considered [2] . Several clinical trials in China have shown chloroquine phosphate, an aminoquinoline used in malaria treatment, to be effective against COVID-19 at a dose of 500 mg/day [3] . Chloroquine phosphate also played a promising role in the management of the Zika virus and SARS-CoV outbreaks. Chloroquine acts by increasing the pH of intracellular vacuoles and altering protein degradation pathways through acidic hydrolases in the lysosomes, macromolecule synthesis in the endosomes, and post-translational protein modification in the Golgi apparatus. In macrophages and other antigen-presenting cells, chloroquine interferes with antigen processing, thereby achieving an antirheumatic response [4] . Studies have demonstrated that chloroquine also confers its considerable broad-spectrum antiviral * Corresponding author. effects via interfering with the fusion process of these viruses by decreasing the pH. In addition, chloroquine alters the glycosylation of the cellular receptors of coronaviruses [5] . Hydroxychloroquine ( Fig. 1 ) , a less toxic aminoquinoline, has an N -hydroxyethyl side chain in place of the N -diethyl group of chloroquine. This modification makes hydroxychloroquine more soluble than chloroquine. Similar to chloroquine, hydroxychloroquine increases the pH and confers antiviral effects. In addition, hydroxychloroquine has a modulating effect on activated immune cells, downregulates the expression of Toll-like receptors (TLRs) and TLR-mediated signal transduction, and decreases the production of interleukin-6 [6] . Although the antimalarial activity of hydroxychloroquine is equivalent to that of chloroquine, hydroxychloroquine is preferred over chloroquine owing to its lower ocular toxicity [7] . Retinopathy is a dose-limiting adverse effect of hydroxychloroquine, and a safe daily dose appears to correspond to 6.5 mg/kg of ideal body weight and 5.0 mg/kg of actual body weight [8] . Although there are more clinical data on the anti-coronaviral activity of chloroquine than that of hydroxychloroquine, both of these agents are theoretically similar in their antiviral activity [9] . Moreover, chloroquine is not as widely available as hydroxychloroquine in some countries. In addition, chloroquine is associated with greater adverse effects than hydroxychloroquine. For example, in patients with COVID-19, chloroquine can interact with lopinavir/ritonavir, resulting in prolongation of the QT interval. Hence, it is necessary to consider hydroxychloroquine instead of chloroquine when the latter is not available for treating patients with COVID-19. For example, in Iran, there is a serious shortage of chloroquine and hydroxychloroquine can be recommended instead. Other therapeutic agents for COVID-19, such as antiviral agents (oseltamivir, lopinavir/ritonavir, ribavirin, etc.), interferons and intravenous immunoglobulins that do not interfere with hydroxychloroquine, are currently under investigation. Funding: None. Open access epidemiological data from the COVID-19 outbreak Chloroquine for the 2019 novel coronavirus SARS-CoV-2 Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases Effects of chloroquine on viral infections: an old drug against today's diseases? Current and future use of chloroquine and hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthalmology guidelines An evaluation of chloroquine as a broad-acting antiviral against hand, foot and mouth disease Ethical Approval: Not required.