• Korean J. Intern. Med. · Jul 2020

    In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.

    • Chang Kyung Kang, Moon-Woo Seong, Su-Jin Choi, Taek Soo Kim, Pyoeng Gyun Choe, Sang Hoon Song, Nam-Joong Kim, Wan Beom Park, and Myoung-Don Oh.
    • Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
    • Korean J. Intern. Med. 2020 Jul 1; 35 (4): 782-787.

    Background/AimsAs the coronavirus disease-2019 global pandemic progresses, screening of antiviral agents effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. In addition, considering the viral load kinetics of SARS-CoV-2, which peaks early in the illness, and the massive burden of the disease, which may increase in the near future, identifying well-tolerated oral antivirals becomes increasingly important. We examined the in vitro activity of lopinavir/ritonavir and hydroxychloroquine on SARS-CoV-2, at concentrations which can be used to treat coronavirus-19 patients with little concern of toxicity.MethodsLopinavir/ritonavir (7/1.75 μg/mL), hydroxychloroquine base (1 or 2 μg/mL), or a combination thereof were administered 1 hour after the inoculation of SARS-CoV-2 to Vero cells at a multiplicity of infection of 0.05. We examined cytopathic effects of virus 48 hours after administration of the respective treatments and measured viral loads at three time points (0, 24, and 48 hours post-treatment) by quantitative real-time reverse-transcription polymerase chain reaction, and compared the results obtained from the different antiviral regimens tested.ResultsThe severity of cytopathic effects was lower in lopinavir/ritonavir-treated cells, and viral load was significantly reduced in this group compared with the control group (p < 0.001). However, hydroxychloroquine did not show significant inhibitory effects on anti-SARS-CoV-2-mediated cytotoxicity or on viral load at either concentration.ConclusionLopinavir/ritonavir showed significant inhibitory effects on SARS-CoV-2 in vitro at its usual plasma concentration. However, the in vitro antiviral activity of hydroxychloroquine at concentrations commonly used in humans was minimal, whether used alone or in combination with lopinavir/ritonavir.

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