Broad-spectrum antiviral peptide targets infectious bronchitis virus S2 subunit to attenuate viral infection and transmission.

Blocking the membrane fusion function mediated by the S2 subunit 6-helix bundle (6-HB) structure is an effective strategy for treating coronavirus infections. However, the 6-HB structure of infectious bronchitis virus (IBV) remains unclear, hindering the development of targeted drugs. In this study, we predicted the 6-HB structure of IBV via in silico and designed an antiviral peptide HR2P based on this structure. This peptide, derived from a conserved HR2 domain identified via amino acid sequence alignment of 511 IBV strains, disrupted IBV-mediated intercellular membrane fusion. The inhibition results demonstrated that HR2P had broad-spectrum inhibitory activity against different IBV strains representing four dominant genotypes in vitro, reducing viral proliferation and replication by 100- to 1000-fold. Notably, the most potent suppression was observed against the IBV Sczy3 strain of the predominant GI-19 genotype. Meanwhile, in vivo treatment with HR2P effectively mitigated IBV infection and reduced horizontal transmission capacity, as evidenced by reduced morbidity and mortality in IBV-infected chickens and alleviated tracheal and kidney damage. Early administration of HR2P showed superior suppression efficacy. Therefore, the HR2P peptide demonstrates potential as a targeted therapeutic agent against IBV, offering a foundation for IBV prevention strategies.