Quaternized Chitosan Derivatives as Viable Antiviral Agents: Structure–Activity Correlations and Mechanisms of Action

Abstract

Cationic polysaccharides have demonstrated significant antimicrobial properties and have great potential in medical applications, where the antiviral activity is of great interest. As of today, alcohols and oxidizing agents are commonly used as antiviral disinfectants. However, these compounds are not environmentally safe, have short activity periods, and may cause health issues. Therefore, this study aimed to develop metal-free and environmentally friendly quaternary chitosans (QCs) with excellent long-lasting virucidal activity. To evaluate this, both single and double QCs were obtained using AETMAC ([2-(acryloyloxy)­ethyl]-trimethylammonium chloride) and GTMAC (glycidyl trimethylammonium chloride) quaternary precursors. Further, this study investigated the influence of the quaternary functional group, charge density, and molecular weight (M w) on the antiviral properties of QCs. It is proposed that the higher charge density, along with the length of alkyl linkers, and hydrophobic interactions affected the antiviral activity of QCs. The findings demonstrated that heterogeneously functionalized chitosan exhibited excellent antiviral activity against both the enveloped virus φ6 and the nonenveloped viruses φX174 and MS2. These quaternized chitosan derivatives have promising potential as viable antiviral agents, as hand/surface sanitizers, or in other biomedical applications.

Dual functional quaternary chitosans with thermoresponsive behavior: structure–activity relationships in antibacterial activity and biocompatibility

“…S2, ESI †). 16,23 The calculated average DDA of chitosan was E74.3%, which is in close agreement with the manufacturer's reported value of Z75%.…”

“…This was consistent with previous determinations. 16,26 Additionally, the change in the downfield shift of the C-6 position from d E 58 ppm in chitosan to d E 62 ppm in QC confirms quaternization.…”

“…Chitosan was quaternized through the graft polymerization of AETMAC onto the chitosan backbones, as described in our previous study. 16 To ensure quaternization in the O-position, Schiff base chitosan served as the starting material. Schiff base chitosan (1.0 g, 4.0 mmol) was dissolved in 2% acetic acid in D 2 O (100 mL) at 80 1C.…”

“…This synthesis route and the antiviral efficacy of the resulting quaternary compounds were explored in our previous study. 16 The primary aim of this work was to improve the quaternization efficiency and study antibacterial activity, biocompatibility, and structure–property relationships. This work demonstrated the superiority of the AETMAC approach over GTMAC in physical properties, solubility, and the property-antibacterial activity relationship against P. syringae and E. coli .…”

Cationic Chitosan Derivatives for the Inactivation of HIV-1 and SARS-CoV-2 Enveloped Viruses

“…The conventional method of making water-soluble, antimicrobial chitosan derivatives involves the introduction of permanent positive charges on the polymer backbone using any of the three reactive centers (the two OH groups and the NH 2 group). ,, The HTCC is one of the most often preferred quaternary chitosan derivatives because of its ease of synthesis, permanent cationic charge, and enhanced microbicidal properties. , It is used in various applications like the medical, paper-making, food, and textile industries as a potent antimicrobial inclusion . We have also previously reported the synthesis, characterization, and antibacterial evaluation of fluorinated HTCC derivatives, which were shown to be effective against various clinically isolated bacterial strains. , Recently, using in vitro and ex vivo models of human airway epithelia, Milewska et al (2021) reported that HTCC has antiviral activity against both MERS-CoV and SARS-CoV-2 infections . Recently, the synthesis, characterization, and antiviral activity of quaternized chitosan derivatives were reported by Teotia et al They concluded that the inhibition of specific interactions between viral-host surface proteins and the destabilization of viral surface proteins, by interactions between viral capsid/envelope and the functional quaternary chitosan, is responsible for the overall activity.…”