Lack of Antiviral Activity of Darunavir against SARS-CoV-2

Abstract

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. 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 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. DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC 50 >100 μ M). Remdesivir, used as a positive control, showed potent antiviral activity (EC 50 = 0.38 μ M). Overall, the data do not support the use of DRV for treatment of COVID-19.

Role of clinical pharmacists in telemonitoring for patients with Coronavirus Disease 2019 (COVID‐19)

“…However, diarrhoea associated with darunavir/ritonavir was still experienced, possibly because of the high doses of darunavir/ritonavir (1200/200 mg/d) used in our setting. More recently, increasing evidence has suggested little benefit of darunavir/ritonavir in COVID‐19 infection, 17 thus use of darunavir/ritonavir was reconsidered. This common ADR could impair absorption of other drugs as well.…”

Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease

“…Recently, approved inhibitors including danoprevir [16] , darunavir [17] , ASC09 [ChiCTR2000029603], lopinavir/ritonavir [ChiCTR2000029539] have been reported to treat COVID-19 patients. At present, as an anti-HIV protease inhibitor, lopinavir/ritonavir has been widely used despite lack of sufficient efficacy data [18] .…”

Clinically relevant cell culture models and their significance in isolation, pathogenesis, vaccine development, repurposing and screening of new drugs for SARS-CoV-2: a systematic review

“…Intestinal ACE-2 receptor expression ( De Meyer et al, 2020 ) and are very susceptible to 2019-nCoV infection. Caco-2 cell line has shown very high CoVs viral titer ( Zhang et al, 2020a ).…”