PBI-0451 + ritonavir

PBI-0451 + ritonavir is an oral, small molecule combination intended for antiviral therapy, primarily targeting **SARS-CoV-2** (COVID-19). PBI-0451 is a **3CL protease inhibitor** (also known as Mpro inhibitor), an investigational antiviral developed to block the main protease of SARS-CoV-2, thus inhibiting viral replication. Ritonavir, a well-established HIV protease inhibitor, is often co-administered in antiviral regimens as a pharmacokinetic booster due to its pronounced inhibition of CYP3A-mediated metabolism, but PBI-0451 appears to have a clearance profile not primarily modifiable by ritonavir. In clinical studies, PBI-0451 has shown potent inhibition of SARS-CoV-2 with favorable oral bioavailability and safety. Early trials of PBI-0451 evaluated pharmacokinetics both as a single agent and in combination with ritonavir, suggesting minimal additional clinical effect by ritonavir but still evaluated as a combination for comparison with other protease inhibitor-based regimens.