Nanchangmycin is a polyether antibiotic that inhibits Gram-positive bacteria and is a growth promoter for ruminants[1]. Nanchangmycin inhibits the activity of the signal peptidase complex responsible for cleaving viral polyproteins, which blocks the cleavage of a Zika virus polyprotein, preventing Zika virus infection[2]. Nanchangmycin has been widely used as an anti-influenza agent to reduce nuclear migration of viral nuclear proteins and suppress influenza A virus infection[3].
In vitro, Nanchangmycin pretreatment for 1 hour inhibited Zika virus infection in U2OS cells, HBMEC cells and Jeg-3 cells, with IC50 values were 0.1µM, 0.4µM, and 0.97µM, respectively[4]. After 72 hours of treatment with Nanchangmycin, the viability of T98G, MeWo, and A-498 cells was significantly inhibited, with IC50 values of 28.2µM, 1.7µM and 71.1µM, respectively[5]. Incubation of mouse primary hematopoietic stem cells with 200nM Nanchangmycin for 48 hours induced lipid accumulation, reduced collagen expression, and increased cytoplasmic Ca2+ concentration[6].
In vivo, Nanchangmycin treatment via oral administration at a dose of 4mg/kg/day for 20 consecutive days inhibited tumor growth in the RPMI-8226 xenograft mouse model without affecting mouse body weight, and decreased c-Maf and Otub1 protein expression in tumor tissues[7].
References:[1] Yu Q, Du A, Liu T, et al. The biosynthesis of the polyether antibiotic nanchangmycin is controlled by two pathway-specific transcriptional activators[J]. Archives of microbiology, 2012, 194(6): 415-426.
[2] Leiva S, Freyermuth C, Claverol S, et al. Affinity-based protein profiling of the antiviral natural product nanchangmycin[J]. RSC Chemical Biology, 2026, 7(1): 129-135.
[3] Zhang H, Liu C, Cai S, et al. Nanchangmycin suppresses influenza A virus infection by blocking endosomal acidification: Nanchangmycin possesses anti-influenza activities[J]. Acta Biochimica et Biophysica Sinica, 2025, 57(10): 1574.
[4] Rausch K, Hackett B A, Weinbren N L, et al. Screening bioactives reveals nanchangmycin as a broad spectrum antiviral active against Zika virus[J]. Cell reports, 2017, 18(3): 804-815.
[5] Huang M, Liu B, Liu R, et al. Aglycone polyether nanchangmycin and its homologues exhibit apoptotic and antiproliferative activities against cancer stem cells[J]. ACS Pharmacology & Translational Science, 2018, 1(2): 84.
[6] Li W, Chen J Y, Sun C, et al. Nanchangmycin regulates FYN, PTK2, and MAPK1/3 to control the fibrotic activity of human hepatic stellate cells[J]. Elife, 2022, 11: e74513.
[7] Xu Y, Sun T, Zeng K, et al. Anti-bacterial and anti-viral nanchangmycin displays anti-myeloma activity by targeting Otub1 and c-Maf[J]. Cell Death & Disease, 2020, 11(9): 818.