Repurposing ritonavir to induce proteasomal degradation of IE1 for inhibition of human cytomegalovirus replication.

Ritonavir induces proteasomal degradation of IE1 protein, reducing human cytomegalovirus replication by over 50% in infected cells.

• Why it matters: HCMV poses a significant threat to immunocompromised patients, and current treatments face issues of toxicity and resistance, especially targeting the undruggable IE1 protein.
• What they did: Using molecular docking and surface plasmon resonance, researchers identified ritonavir binding to IE1, promoting its degradation via the ubiquitin-proteasome pathway and inhibiting viral replication in vitro.
• The result: Ritonavir effectively decreases viral DNA loads and infectious particles, shows synergy with ganciclovir, and offers a promising repurposed therapy for HCMV infection.