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

Abstract

Background/Aims As 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. Methods Lopinavir/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. Results The 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. Conclusions Lopinavir/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.

Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study

“…One possible reason is that a higher dose is required to successfully suppress SARS-CoV-2 in patients as shown in vitro cytotoxicity test ( Cao et al, 2020 , Keyaerts et al, 2004 , Wang et al, 2020 ). In particular, the in vitro antiviral activity of HCQ at concentrations commonly used in humans was reported minimal ( Kang et al, 2020 ). Insufficient data are available regarding the optimal dose to ensure the safety and efficacy of both drugs for COVID-19.…”

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

“…Choy et al (305) were successful at demonstrating the antiviral effect of lopinavir against SARS-CoV-2, but this was not the case for ritonavir. In turn, Kang et al (306) found a lower viral load in infected SARS-CoV-2 Vero cells treated with lopinavir/ritonavir in relation to the untreated infected control. Although no consensus has been reached on its efficacy, dosage, or administration period, the literature includes some case reports, case series, and observational studies reporting a protective effect of the lopinavir/ritonavir combination in COVID-19 patients (110,(307)(308)(309)(310)(311)(312).…”

Biochemical and Computational Approach of Selected Phytocompounds from Tinospora crispa in the Management of COVID-19

“…Previously, another study from Yamamoto et al reported the inhibitory effect of nelfinavir on the replication of SARS-CoV [ 55 ]. In addition, another in vitro analysis showed that lopinavir/ritonavir exhibited potential inhibitory effects on SARS-CoV-2 [ 56 ]. Hence, we selected nelfinavir and lopinavir as positive controls in the present study.…”