Abstract

Enveloped viruses rely on specialized membrane-active proteins, primarily fusion proteins, to facilitate entry into host cells by merging the viral and cellular lipid bilayers. This review is dedicated to analyzing the **physico-chemical mechanisms** governing the function of these essential structural proteins across a range of enveloped viruses. The primary objective is to synthesize current knowledge regarding the molecular events and biophysical principles that drive the membrane activity of these proteins at various stages of the viral infection cycle. Key mechanisms investigated include the protein's conformational changes, the role of their hydrophobic domains (fusion peptides) in membrane insertion, and the resulting localized membrane curvature and destabilization that precedes fusion pore formation. Furthermore, the review examines the influence of environmental factors, such as pH and receptor binding, on triggering the protein's metastable state. Understanding these fundamental physico-chemical principles is crucial for developing targeted antiviral strategies that specifically inhibit the membrane-active function of these proteins, thereby blocking viral entry and subsequent infection. This comprehensive analysis highlights common themes and distinct variations in the viral membrane fusion machinery, providing a foundation for future research in membrane and cell biology.