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      The Use of Antimalarial Drugs against Viral Infection

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          Abstract

          In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.

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          Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel Lecture).

          Youyou Tu (2016)
          Malaria has long been a devastating and life-threatening global epidemic disease in human history. Artemisinin, the active substance against malaria, was first isolated and tested in the 1970s in China. The important role played by traditional Chinese medicine in the discovery of artemisinin is described by Y. Tu in her Nobel Lecture.
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            Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

            Jane Achan, Ambrose O Talisuna, Annette Erhart … (2011)
            Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.
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              Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice.

              Els Keyaerts, Sandra Li, Leen Vijgen … (2009)
              Until recently, human coronaviruses (HCoVs), such as HCoV strain OC43 (HCoV-OC43), were mainly known to cause 15 to 30% of mild upper respiratory tract infections. In recent years, the identification of new HCoVs, including severe acute respiratory syndrome coronavirus, revealed that HCoVs can be highly pathogenic and can cause more severe upper and lower respiratory tract infections, including bronchiolitis and pneumonia. To date, no specific antiviral drugs to prevent or treat HCoV infections are available. We demonstrate that chloroquine, a widely used drug with well-known antimalarial effects, inhibits HCoV-OC43 replication in HRT-18 cells, with a 50% effective concentration (+/- standard deviation) of 0.306 +/- 0.0091 microM and a 50% cytotoxic concentration (+/- standard deviation) of 419 +/- 192.5 microM, resulting in a selectivity index of 1,369. Further, we investigated whether chloroquine could prevent HCoV-OC43-induced death in newborn mice. Our results show that a lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with chloroquine acquired transplacentally or via maternal milk. The highest survival rate (98.6%) of the pups was found when mother mice were treated daily with a concentration of 15 mg of chloroquine per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg chloroquine and 13% survival when treated with 1 mg/kg chloroquine. Our results show that chloroquine can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Microorganisms
                Journal ID (iso-abbrev): Microorganisms
                Journal ID (publisher-id): microorganisms
                Title: Microorganisms
                Publisher: MDPI
                ISSN (Electronic): 2076-2607
                Publication date (Electronic): 08 January 2020
                Publication date Collection: January 2020
                Volume: 8
                Issue: 1
                Electronic Location Identifier: 85
                Affiliations
                [1 ]Department of Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milan, Italy; sarah.dalessandro@ 123456unimi.it (S.D.); lucia.signorini@ 123456unimi.it (L.S.); federica.perego@ 123456unimi.it (F.P.); pasquale.ferrante@ 123456unimi.it (P.F.)
                [2 ]Department of Pharmacological and Biomolecular Sciences, University of Milano, 20133 Milan, Italy; diletta.scaccabarozzi@ 123456unimi.it
                [3 ]Département des Sciences de la Vie, University of Fada N’Gourma (UFDG), Fada N’Gourma BP 54, Burkina Faso; denise.ilboudo@ 123456gmail.com
                Author notes
                [* ]Correspondence: serena.delbue@ 123456unimi.it ; Tel.: +39-02-50315070
                Author information
                https://orcid.org/0000-0001-9241-9762
                https://orcid.org/0000-0001-8881-898X
                https://orcid.org/0000-0003-1566-0231
                https://orcid.org/0000-0002-3199-9369
                Article
                Publisher ID: microorganisms-08-00085
                DOI: 10.3390/microorganisms8010085
                PMC ID: 7022795
                PubMed ID: 31936284
                SO-VID: c23c7873-cbd3-44b2-99f2-376689633fd3
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 11 December 2019
                Date accepted : 03 January 2020
                Categories
                Subject: Review

                Keywords: antimalarial drugs,viruses,emerging infections
                Data availability:
                Keywords: antimalarial drugs, viruses, emerging infections

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