VIP

VIP is an endogenous neuropeptide with broad vasoactive, pulmonary, gastrointestinal, and immunomodulatory functions. The main synthetic therapeutic analog in the literature is aviptadil (Zyesami). It remains investigational in the U.S. rather than FDA-approved.

Recent reviews describe aviptadil as binding VPAC1 and VPAC2 receptors, which are abundant on alveolar type II cells. The proposed mechanism includes helping preserve alveolar barrier function, reducing inflammatory signaling, and supporting surfactant-related lung biology. Clinical literature is mixed: some reviews summarize trends toward improved oxygenation and inflammatory markers, and some inhaled studies report faster recovery signals, but negative or equivocal randomized evidence also exists and survival benefit remains unproven.