Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

Abstract

An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

Keywords: ABSTRACT; COVID-19; Emetine; Homoharringtonine; Lopinavir; Remdesivir; Ritonavir.

Fig. 1

Antiviral activity of remdesivir (A), lopinavir (B), homorringtonine (C) and emetine dihydrochloride (D) against SARS-CoV-2 virus in vitro. Infectious viral loads (log₁₀TCID₅₀/mL left Y axis) and viability (normalized to the ATP level of the Vero E6 cells incubated with infection media) under increasing concentrations of the antiviral compounds are shown.

Fig. 2

Combinational effect of remdesivir and emetine dihydrochloride against SARS-CoV-2 virus in vitro. (A) Dose response matrix of serially 2-fold diluted remdesivir (0–50 μM) and emetine (0–0.781 μM) in Vero E6 cells. The percentage of viral inhibition was normalized based on viral load in logarithm scale (log₁₀RNA copies/mL), using the maximal viral RNA copies with no drug controls as 0% inhibition and the minimal RNA copies determined at 50 μM remdesivir as references. (B) The three-dimensional interaction landscapes of remdesivir and emetine were generated by SynergyFinder (Ianevski et al., 2017) based on (B) the Loewe additive model and (C) the Bliss independence model. Red colour indicates synergy while the green colour indicates antagonism of the two drugs.