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  1. Fulltext Repurposing Antimalarials to Tackle the COVID-19 Pandemic
    Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, et al.
    Trends Parasitol, 2021 01;37(1):8-11.
    PMID: 33153922 DOI: 10.1016/j.pt.2020.10.003
    Artemisinin-based combination therapies (ACTs) have demonstrated in vitro inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Artemisinins have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe coronavirus disease 2019 (COVID-19). There is now sufficient evidence for the effectiveness of ACTs, and in particular artesunate/pyronaridine, to support clinical studies for COVID-19 infections.
  2. Drug repurposing for COVID-19: current evidence from randomized controlled adaptive platform trials and living systematic reviews
    Augustin Y, Staines HM, Velavan TP, Kamarulzaman A, Kremsner PG, Krishna S
    Br Med Bull, 2023 Sep 12;147(1):31-49.
    PMID: 37312588 DOI: 10.1093/bmb/ldac037
    INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally.

    SOURCES OF DATA: Recent published literature.

    AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.

    AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.

    GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.

    AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.

  3. Fulltext Susceptibility of human Plasmodium knowlesi infections to anti-malarials
    Fatih FA, Staines HM, Siner A, Ahmed MA, Woon LC, Pasini EM, et al.
    Malar J, 2013;12:425.
    PMID: 24245918 DOI: 10.1186/1475-2875-12-425
    Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. Therefore, adequate response to available anti-malarial treatments is assumed.
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