Past outbreaks of enveloped viruses, including SARS-CoV-2, underscore the need for personal protective equipment (PPE), enhanced with antiviral agents to mitigate fomite-based viral transmission. Building on quaternary chitosan (HTCC) and tannic acid (TA), this work introduces a novel aqueous HTCC/TA-based nanoformulation (i.e., HTCC/TA-NPs) as a potential biopolymeric colloidal antiviral agent for protective coatings. Surface charge, size, morphology, crystal structure, surface chemistry, antiviral activity, TA release, antioxidative potential, biocompatibility, and thermogravimetric traits were characterized for HTCC/TA-NPs, HTCC-NPs, and their constituents. We systematically examine their pH-dependent physicochemical properties, implications for application-relevant behavior and antiviral performance, evaluated at physiological pH 7.5 for surface-coating relevance. Extensive characterization confirmed nanoparticle (NP) formation at optimal pH and sufficient surface charge at physiological pH for expected antiviral interactions, evidenced by > 3.5 log10 PFU/mL inactivation and altered virus morphology after 18 h (TEM). These observations suggest envelope disruption, viral binding and entrapment via a multifaceted antiviral mechanism mediated by charge and short-range physicochemical interactions. Results demonstrate HTCC/TA-NPs’ biocompatibility and antiviral potential, while elucidating the physicochemical origin of their antiviral mechanisms against the enveloped virus phi6, a SARS-CoV-2 surrogate. These insights may accelerate development of new biocompatible PPE coatings and highlight HTCC/TA-NPs as a green, noncytotoxic approach for functional protective surfaces, with efficacy governed by comprehensive structure-activity dependent relationships.
