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The combination of valacyclovir, celecoxib, and Paxlovid (nirmatrelvir/ritonavir) is an investigational therapeutic regimen being developed by PridCor Therapeutics for the treatment of Long COVID (post-acute sequelae of COVID-19). Also known as the PridCor Protocol or CAR (combination antiviral regimen), this therapy is designed to simultaneously address two hypothesized biological drivers of Long COVID: persistent SARS-CoV-2 viral reservoirs and the reactivation of latent herpesviruses (such as Epstein-Barr virus). The regimen utilizes IMC-2 (a fixed-dose combination of the antiviral valacyclovir and the selective COX-2 inhibitor celecoxib) as a continuous base therapy, with a pulsed course of Paxlovid added to target SARS-CoV-2. Valacyclovir inhibits herpesvirus DNA polymerase, celecoxib reduces inflammation and synergistically blocks herpesvirus replication, and nirmatrelvir inhibits the SARS-CoV-2 3C-like protease (boosted by ritonavir's inhibition of CYP3A4). The combination is currently being evaluated in the Phase 2 SHIELD clinical trial (NCT07597902) in collaboration with the Icahn School of Medicine at Mount Sinai.
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