An Update on Theoretical and Metrological Aspects of the Surface Hydrophobicity of Virus and Virus‐Like Particles

Viruses are biological entities embodied in protein-based nanoparticles devoid of metabolic activity. Hence, the colloidal, interfacial, and chemical reactivity of virus particles (VPs) profoundly affects the fate of natural and artificial viruses in biotic or abiotic aqueous systems. These rely on the physical chemistry at the outer surface of VPs. In other words, whether wild or synthetic VPs and regardless of the scientific fields involved, taming viruses implies thus managing the physical chemistry at the VP external surface. The surface hydrophobicity (SH) of VPs is a critical feature that must be looked at. Still, the literature dealing with nanoscale hydrophobic domains at the proteinaceous surface of VPs underlying their global SH is like a fragmented puzzle. This article provides an overview of the topic from the perspective of modern protein biophysics for updating the classic physicochemical picture of outer VP/water interfaces hitherto accepted. Patterns of non-polar and "false-polar" patches, expressing variable hydrophobic degrees according to neighboring polar patches, are now drawn. The extensive discussion of reviewed data generates such fresh ideas to explore in the coming years for better modeling the SH of wild virions or engineered virus-based nanoparticles, paving the way for new directions in fundamental virology and virus-based chemistry.