key: cord-0811837-agc89fqv authors: Serafin, Marissa B.; Bottega, Angelita; Foletto, Vitória S.; da Rosa, Taciéli F.; Hörner, Andreas; Hörner, Rosmari title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19 date: 2020-04-09 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2020.105969 sha: 9e38a1b572034071df752844aaed131a5893209b doc_id: 811837 cord_uid: agc89fqv Abstract Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease. Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease. © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. The recent spread of the novel coronavirus, SARS-CoV-2 has created a worldwide public health emergency. In December 2019, the outbreak of this emerging disease (COVID-19) began in Wuhan, China. It quickly spread, and a pandemic was declared by the World Health Organization in March 2020 [1 , 2] . Repositioning drugs already approved for use in humans is a useful tool to search for new therapeutic options, particularly in the current global crisis [3] . Thus, drug repositioning, also known as redirecting, repurposing, and reprofiling [4 , 5] , emerges as an effective possibility for generating new treatments against COVID-19. Repositioning is defined as a new use of a drug, in addition to its original indication(s), and is an option for rapid identification of new therapeutic agents. The availability of drugrelated information, such as pharmacokinetics, pharmacodynamics and toxicity [6] , is an important advantage in the research effort s to quickly find an effective treatment for this deadly virus. Table 1 presents a selection of recent studies that investigated the antiviral activity of several pharmacological classes, including antimalarial drugs and antibiotics, as options for repositioning as treatments of coronavirus (SARS-CoV, SARS-CoV-2 and HCoV-OC43) [7] [8] [9] [10] . A search was conducted on three databases (PubMed, SCOPUS and Web of Science) be- ] with review filters appropriate for individual databases. The inclusion criterion was studies that included the repositioning of drugs with antiviral activity against coronavirus. Duplicate cases were excluded, as were studies that did not address the issue. The analysis revealed seven studies that address drug repositioning against SARS-CoV-2; the target drugs were chloroquine, hydroxychloroquine associated with azithromycin, teicoplanin, remdesivir, nitazoxanide and metformin. Several authors report the potential of chloroquine as a therapeutic option against this virus: in vitro it presented an EC 50 of 1.13 μm and in vivo it caused a negative conversion of the virus in more than 100 patients who were participating in multicenter clinical trials conducted in China [7 , 8] . In the in vitro study performed by Liu et al. (2020) , both chloroquine and hydroxychloroquine inhibited the virus from entering the cell and, at later cell stages of SARS-CoV-2 infection, blocked virus transport between cell organelles, which is considered a determining step for the release of viral genome in cells in the case of SARS-CoV-2. However, chloroquine was observed to have a higher efficacy [9] . Teicoplanin, on the other hand, presented an in vitro IC 50 of 1.66 μM, a relatively low active concentration, which is promising for its use against SARS-CoV-2; however, this requires further in vivo verification and incorporation in clinical trials [10] . (-) Not determined Gautret et al. (2020) conducted a clinical trial using hydroxychloroquine in patients infected with SARS-CoV-2. The initial results show a significant reduction in viral carriage and the use of hydroxychloroquine in conjunction with azithromycin was more efficient in eliminating the virus [11] . There is also expectation for the results of the WHO solidarity initiative, which consisted of a worldwide call for a clinical study to simultaneously research the efficacy of four drugs, including remdesivir, chloroquine and hydroxychloroquine, for the treatment of patients affected with COVID-19 [12] . Thus, drug repositioning is a promising alternative for the treatment of COVID-19 disease, and a more complex investigation of the antiviral effect of these molecules against SARS-CoV-2 is encouraged. Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Brasil (CAPES) -Finance Code 001. World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 A review of the 2019 novel coronavirus (COVID-19) based on current evidence Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19? Drug repositioning, a new alternative in infectious diseases Repositioning of fluoxetine and paroxetine: study of potential antibacterial activity and its combination with ciprofloxacin Drug repurposing screens and synergistic drug-combinations for infectious diseases 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 Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro JID: ANTAGE [m5G Teicoplanin potently blocks the cell entry of 2019-nCoV Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 Repurposing of clinically developed drugs for treatment of Middle East Respiratory Syndrome coronavirus infection Inhibitors of RAS might be a good choice for the therapy of COVID-19 pneumonia In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East Respiratory Syndrome coronavirus replication in cell culture In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) A SARS-CoV-2-human protein-protein interaction map reveals drug targets and potential drug-repurposing Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice Cyclosporin A inhibits the replication of diverse coronaviruses The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes The authors report no conflicts of interest.Ethical Approval : Not required