Lack of antiviral activity of darunavir against SARS-CoV-2

Abstract

Objectives: Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives.

Methods: Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for the treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed.

Results: DRV showed no antiviral activity against SARS-CoV-2 at clinically relevant concentrations (EC₅₀ > 100 μM). Remdesivir, used as a positive control, demonstrated potent antiviral activity (EC₅₀ = 0.38 μM).

Conclusions: Overall, the data do not support the use of DRV for the treatment of COVID-19.

Keywords: COVID-19; Darunavir; In vitro; SARS-CoV-2.

Figure 1

Inhibition of SARS-CoV-2 in Caco-2 cells by cytopathogenic effect assay using a visual read-out (visual CPE read-out) and MTT assay (MTT) following the addition of a) remdesivir, or b) darunavir (DRV). Cytotoxicity data (measured on uninfected cells) are also shown. Mean percent inhibition for each read-out across three independent experiments with triplicate measurements are plotted (2 independent experiments for the MTT assay). The error bars represent the standard deviation. Note: for some points, the error bars are shorter than the height of the symbol. (a) Visual CPE-read out EC₅₀ = 0.11 μM; MTT EC₅₀ = 0.38 μM; CC₅₀ >100 μM; Selectivity index = >900 (Visual CPE read-out); >260 (MTT). (b) Visual CPE read-out EC₅₀ > 100 μM; MTT EC₅₀ >100 μM; CC₅₀ >100 μM.