population PBPK/PD

Darunavir is a synthetic nonpeptidic inhibitor of protease and was developed to increase interaction with HIV-1 protease and to be more resistant against HIV-1 protease mutations. It was initially considered as a promising antiviral treatment for COVID-19. However, in two recent in vitro studies (De Meyer 2020, Touret 2020), darunavir showed low to no antiviral activity against SARS-CoV-2, the virus that caused COVID-19, at clinically relevant concentrations.

Johnson and Johnson released a position statement that did not support the use of darunavir in COVID-19.

Specifically, Janssen has no clinical nor pharmacological evidence to support the inclusion of DRV/cobicistat in treatment guidelines for COVID-19, nor are there published data on the safety and efficacy profile of DRV/cobicistat in treatment of COVID-19. There are no published clinical studies that have evaluated the efficacy and safety of DRV, DRV/cobicistat or DRV/cobicistat/emtricitabine/tenofovir alafenamide for the treatment of novel coronavirus. Many Janssen compounds, including darunavir, are in the process of being evaluated in-vitro for potential antiviral activity against SARS-CoV-2. The in-vitro antiviral activity of DRV against SARS-CoV-2 was assessed. DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100 μM). These data do not support the use of DRV for treatment of COVID-19. Results from a single center, open label, randomized, and controlled trial conducted at Shanghai Public Health Clinical Center (SPHCC) of darunavir and cobicistat (DRV/c) in treating laboratory-confirmed 30 COVID-19 patients showed that DRV/c was not effective. Additionally, structural analyses show very few interactions of DRV with the active site of the SARS-CoV-2 protease.

The in silico workbench is intended for use by researchers to assist with clinical trial design and for exploratory and educational purposes. It is NOT intended for use in the diagnosis, cure, mitigation or treatment of any disease. Data provided are not intended to suggest that any product and/or dosing regimen are safe and effective for any use and are for informational purposes only. Please see Terms and Conditions for additional information.