High molecular weight chitosan (HMWCh), quaternised cellulose nanofibrils (qCNF), and their mixture showed antiviral potential in liquid phase, while this effect decreased when applied to facial masks, as studied in our recent work. To gain more insight into material antiviral activity, spin-coated thin films were prepared from each suspension (HMWCh, qCNF) and their mixture with a 1:1 ratio. To understand their mechanism of action, the interactions between these model films with various polar and nonpolar liquids and bacteriophage phi6 (in liquid phase) as a viral surrogate were studied. Surface free energy (SFE) estimates were used as a tool to evaluate the potential adhesion of different polar liquid phases to these films by contact angle measurements (CA) using the sessile drop method. The Fowkes, Owens–Wendt–Rabel–Kealble (OWRK), Wu, and van Oss–Chaudhury–Good (vOGC) mathematical models were used to estimate surface free energy and its polar and dispersive contributions, as well as the Lewis acid and Lewis base contributions. In addition, the surface tension SFT of liquids was also determined. The adhesion and cohesion forces in wetting processes were also observed. The estimated SFE of spin-coated films varied between mathematical models (26–31 mJ/m2) depending on the polarity of the solvents tested, but the correlation between models clearly indicated a significant dominance of the dispersion components that hinder wettability. The poor wettability was also supported by the fact that the cohesive forces in the liquid phase were stronger than the adhesion to the contact surface. In addition, the dispersive (hydrophobic) component dominated in the phi6 dispersion, and since this was also the case in the spin-coated films, it can be assumed that weak physical van der Waals forces (dispersion forces) and hydrophobic interactions occurred between phi6 and the polysaccharide films, resulting in the virus not being in sufficient contact with the tested material during antiviral testing of the material to be inactivated by the active coatings of the polysaccharides used. Regarding the contact killing mechanism, this is a disadvantage that can be overcome by changing the previous material surface (activation). In this way, HMWCh, qCNF, and their mixture can attach to the material surface with better adhesion, thickness, and different shape and orientation, resulting in a more dominant polar fraction of SFE and thus enabling the interactions within the polar part of phi6 dispersion.