As a host-targeting, oral antiviral drug candidate, brequinar blocks de novo pyrimidine biosynthesis, a pathway involved in DNA and RNA metabolism. In vitro and in vivo studies have shown that brequinar has potent antiviral activity against a wide range of viruses, including SARS-CoV-2.
Because brequinar acts on the host cell, it has the potential to deliver broad-spectrum antiviral activity either as a standalone therapy or in combination with direct-acting antiviral drugs, such as nucleoside analogs.
Clear Creek Bio is focused on rapidly developing brequinar as an antiviral for COVID-19 and other viruses with pandemic potential.
PLpro is a SARS-CoV-2 encoded protease whose catalytic activity is essential to fully process the viral polyprotein and assemble a functional replicase complex.
In addition to this critical role in viral replication, PLpro is a unique viral protease that cleaves important host regulators of innate immunity such as ISG15, resulting in dampened antiviral immune mechanisms.
PLpro inhibitors have the potential to be unique and efficacious therapeutics for COVID-19 that directly block viral replication and simultaneously enhance antiviral immunity. Clear Creek Bio is advancing its PLpro program to nominate a development candidate in 2022.