tetano
Editor, Senior Moderator
J Med Chem
. 2026 Feb 26.
doi: 10.1021/acs.jmedchem.5c03547. Online ahead of print.
Zanamivir-Amantadine Conjugate: A Dual-Action Agent with Broad-Spectrum Synergistic Antiviral Efficacy
Yiming Wang[SUP] 1 2 3 [/SUP], Liwen Hua[SUP] 1 2 [/SUP], Honggao Duan[SUP] 1 4 2 [/SUP], Ruiwen Liu[SUP] 1 2 [/SUP], Mengyang Wang[SUP] 1 2 [/SUP], Peng Zhao[SUP] 1 2 3 [/SUP], Tao Yuan[SUP] 1 2 3 [/SUP], Yiping Zhong[SUP] 1 2 3 [/SUP], Rui Feng[SUP] 1 2 [/SUP], Xingxing Zhu[SUP] 1 2 3 [/SUP], Yongmin Zhang[SUP] 5 6 [/SUP], Demin Zhou[SUP] 1 4 2 3 [/SUP], Sulong Xiao[SUP] 1 4 2 3 5 [/SUP]
Affiliations
Influenza A virus is a highly contagious respiratory pathogen, and its rapid and continuous adaptive mutations for immune escape have limited the efficacy of existing vaccines and antiviral drugs. Here, we report a multimechanism anti-influenza platform based on the conjugation of zanamivir (ZMV) with amantadine (Aman). Aman acts as a hydrophobic tag that promotes the degradation of neuraminidase and concurrently enhances the physicochemical properties of ZMV, leading to improved membrane permeability and a significantly prolonged half-life. Meanwhile, the ZMV moiety counteracts Aman-induced cytotoxic autophagy. The resulting conjugate, compound 7j, exhibits potent activity against a wide range of neuraminidase and M2 ion channel mutations. Notably, a single intravenous dose of 7j fully protected mice from a lethal H1N1 challenge. Our work demonstrates that the rational fusion of ZMV and Aman achieves synergistic multimechanistic antiviral activity with enhanced efficacy and safety, offering a new strategy for the development of next-generation anti-influenza drugs.
. 2026 Feb 26.
doi: 10.1021/acs.jmedchem.5c03547. Online ahead of print.
Zanamivir-Amantadine Conjugate: A Dual-Action Agent with Broad-Spectrum Synergistic Antiviral Efficacy
Yiming Wang[SUP] 1 2 3 [/SUP], Liwen Hua[SUP] 1 2 [/SUP], Honggao Duan[SUP] 1 4 2 [/SUP], Ruiwen Liu[SUP] 1 2 [/SUP], Mengyang Wang[SUP] 1 2 [/SUP], Peng Zhao[SUP] 1 2 3 [/SUP], Tao Yuan[SUP] 1 2 3 [/SUP], Yiping Zhong[SUP] 1 2 3 [/SUP], Rui Feng[SUP] 1 2 [/SUP], Xingxing Zhu[SUP] 1 2 3 [/SUP], Yongmin Zhang[SUP] 5 6 [/SUP], Demin Zhou[SUP] 1 4 2 3 [/SUP], Sulong Xiao[SUP] 1 4 2 3 5 [/SUP]
Affiliations
- PMID: 41744161
- DOI: 10.1021/acs.jmedchem.5c03547
Influenza A virus is a highly contagious respiratory pathogen, and its rapid and continuous adaptive mutations for immune escape have limited the efficacy of existing vaccines and antiviral drugs. Here, we report a multimechanism anti-influenza platform based on the conjugation of zanamivir (ZMV) with amantadine (Aman). Aman acts as a hydrophobic tag that promotes the degradation of neuraminidase and concurrently enhances the physicochemical properties of ZMV, leading to improved membrane permeability and a significantly prolonged half-life. Meanwhile, the ZMV moiety counteracts Aman-induced cytotoxic autophagy. The resulting conjugate, compound 7j, exhibits potent activity against a wide range of neuraminidase and M2 ion channel mutations. Notably, a single intravenous dose of 7j fully protected mice from a lethal H1N1 challenge. Our work demonstrates that the rational fusion of ZMV and Aman achieves synergistic multimechanistic antiviral activity with enhanced efficacy and safety, offering a new strategy for the development of next-generation anti-influenza drugs.