2025/10/21 by Santiago Leiva, Chloé Freyermuth, Stéphane Claverol +2 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Monoclonal and Polyclonal Antibodies Research #Glycosylation and Glycoproteins Research #Microbial Natural Products and Biosynthesis
paper · pdf · doi:10.1039/d5cb00126a
openalex publication_date 2025/10/21 · openalex created_date 2025/10/22 · openalex updated_date 2026/07/28
Nanchangmycin is a natural product with broad-spectrum activity against various organisms, exhibiting antibiotic, antiviral, anticancer, and antifibrotic effects. Nanchangmycin belongs to the family of polyether ionophores and is proposed to exert its therapeutic effects by altering ion gradients across biological membranes. Although this therapeutic mechanism has been well characterised in cancer models, it does not fully explain how nanchangmycin inhibits Zika virus infection, as recently reported. The specific molecular targets responsible for mediating nanchangmycin's antiviral activity remain unknown. Here, we designed a photoreactive clickable nanchangmycin probe and employed chemical proteomics to identify protein targets of nanchangmycin related to Zika virus infection in human cells. Among the most prominent targets was the protein SEC11A, a key component of the signal peptidase complex, which is essential for cleaving and processing Zika virus proteins. We showed that nanchangmycin blocks the cleavage of a Zika virus polyprotein, suggesting a novel mechanism for nanchangmycin-mediated inhibition of Zika virus infection.