Combinatorial Synthesis of Next Generation Water‐Soluble Quaternized N‐Halamine Oligomers with Long‐Lasting Antiviral Properties

Abstract Throughout human history, several pandemics have caused the deaths of millions of people worldwide. The recent emergence of highly contagious severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants underscores the urgent need for effective measures to protect surfaces from viral transmission to restrict the spread of coronavirus disease 2019 (COVID‐19) infection. However, the absence of long‐lasting antiviral materials in combating the COVID‐19 pandemic is clearly necessitating constant surface disinfection, which in turn lies on small molecule‐based surface decontamination. Herein, a combinatorial synthesis library of novel antiviral oligomers containing both N‐halamine and quaternary ammonium functionalities with long‐lasting bleaching properties to combat the spread of SARS‐CoV‐2 (including wild type, XBB1.5 and JN.1 variants) and the seasonal influenza virus (H1N1) is reported. Compared to household bleach, the most active oligomers exhibit superior antiviral activity that achieve over 99.8% efficacy against SARS‐CoV‐2 spikes at significantly lower concentrations. Additionally, the leading oligomers demonstrate rapid deactivation of the viruses and maintain superior activity (4 to 5 log reduction in viral copies) compared to household bleach on various surfaces for extended periods. Moreover, these oligomers are non toxic toward human lung epithelial cells and human keratinocytes, highlighting their potential as safe and efficient disinfection alternatives for future viral pandemics.