PROTAC targeting cyclophilin A controls virus-induced cytokine storm.

ABSTRACT: Cytokine storms caused by viruses are associated with elevated cytokine levels and uncontrolled inflammatory responses that can lead to acute respiratory distress syndrome. Current antiviral therapies are not sufficient to prevent or treat these complications. Cyclophilin A (CypA) is a key factor that regulates the production of multiple cytokines and could be a potential therapeutic target for cytokine storms. Here, three proteolysis targeting chimeras (PROTACs) targeting CypA were designed. These PROTACs bind to CypA, enhance its ubiquitination, and promote its degradation in both cell lines and mouse organs. During influenza B virus (IBV) infection, PROTAC-mediated CypA depletion reduces P65 phosphorylation and NF-κB-mediated proinflammatory cytokine production in A549 cells. Moreover,

SUBMITTER: Li H 

PROVIDER: S-EPMC10448112 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature