Synergistic antiviral potential of N-(2-hydroxy)propyl-3-trimethylammoniumchitosan-functionalized silver nanoparticles with oseltamivir against influenza a viruses

Ping-Cheng Liu; Tein-Yao Chang; Xin-An Chen; Chih-Chia Cheng; Chih-Heng Huang; An-Yu Chen; Shan-Ko Tsai; Jenn-Jong Young; Cheng-Cheung Chen

doi:10.1016/j.ijbiomac.2024.137996

Synergistic antiviral potential of N-(2-hydroxy)propyl-3-trimethylammoniumchitosan-functionalized silver nanoparticles with oseltamivir against influenza a viruses

Int J Biol Macromol. 2024 Nov 23:137996. doi: 10.1016/j.ijbiomac.2024.137996. Online ahead of print.

Authors

Ping-Cheng Liu¹, Tein-Yao Chang², Xin-An Chen³, Chih-Chia Cheng⁴, Chih-Heng Huang⁵, An-Yu Chen⁶, Shan-Ko Tsai⁶, Jenn-Jong Young⁷, Cheng-Cheung Chen⁸

Affiliations

¹ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC.
² Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 11490, Taiwan, ROC.
³ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC; Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC.
⁴ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC; Advanced Membrane Materials Research Center, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC.
⁵ Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, Taiwan, ROC; Department of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan, ROC.
⁶ Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, Taiwan, ROC.
⁷ Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Biodefense, National Defense Medical Center, Taipei 11490, Taiwan, ROC.
⁸ Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, Taiwan, ROC; Graduate Institute of Biodefense, National Defense Medical Center, Taipei 11490, Taiwan, ROC. Electronic address: chengcheung_chen@mail.ndmctsgh.edu.tw.

PMID: 39586441
DOI: 10.1016/j.ijbiomac.2024.137996

Abstract

This study introduced a novel antiviral approach by combining three substances with different antiviral mechanisms: N-(2-hydroxy)propyl-3-trimethylammoniumchitosan (HTC), silver nanoparticles (AgNPs), and oseltamivir. First, positively surface-charged AgNPs were prepared using an environmentally friendly method. The surfaces of these AgNPs were capped with cationic quaternary chitosan HTC. It exhibits a positive zeta potential with extraordinary stability in aqueous solutions and facilitates substantial and rapid cellular uptake including entry into the cell nucleus. HTC-AgNPs display broad-spectrum antiviral activity against three influenza A viruses (H5N1, H3N2, and H1N1) at biocompatible concentrations. When blended with oseltamivir, HTC-AgNPs enhances the antiviral activity from that of oseltamivir alone by at least 20 times. After 24 h of combined treatment, the inhibition efficiency against influenza A virus can attain up to 99.9 %. We anticipate that this combination could reduce the effective dose of Tamiflu by 10-fold when used in clinic, thus shortening recovery period and lowering the medication costs. Moreover, the synergistic effects of the three active substances would reduce the likelihood of the emergence of drug-resistant viral strains. This would, in turn, enhance the effectiveness and safety of this medication.

Keywords: Antiviral activity; Influenza a virus; Oseltamivir; Quaternary chitosan; Silver nanoparticles; Synergistic effect.