Viral Envelope Membrane: A Special Entry Pathway and a Promising Drug Target

Enveloped viruses are a large class of pathogens responsible for multiple serious diseases. Their spread to new territories has been the cause of major epidemics throughout human history, including the Spanish flu in 1918 and the latest COVID-19 pandemic. Thanks to their outer mem-brane, consisting essentially of host lipids, enveloped viruses are more resistant to enzymes, and are also less susceptible to host immune defenses than their naked counterparts. Therefore, the development of effective approaches to combat enveloped virus infections represents a major chal-lenge for antiviral therapy in the current century. This review focuses on the characteristics of enveloped viruses, their importance in the entry phase, drugs that target envelope membrane-mediated entry, and those specifically designed to target the envelope. The advantages in terms of selectivity and reduced drug-resistance can be attributed to the ability to affect the envelope, an essential structural feature common to several viruses, which makes this class of compounds broad-spectrum antivirals, agents of great interest when no specific drugs or vaccines are available to block viral infections.