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

Abstract

Enveloped viruses belong to a large class of pathogens responsible for multiple serious diseases. Their spread into 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 membrane, 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 challenge for antiviral therapy in the current century. This review focuses on the characteristics of enveloped viruses, their importance in the entry phase, drugs targeting envelope membrane-mediated entry, and those specifically designed to target the envelope. The broad-spectrum antiviral activity of these compounds can be attributed to their ability to affect the envelope, an essential structural feature common to several viruses. This makes this class of compounds agents of great interest when no specific drugs or vaccines are available to block viral infections.

Cationic Perylene Antivirals with Aqueous Solubility for Studies In Vivo

“…Additionally, targeting the viral envelope is attractive due to the anticipated rate of resistance development being negligible. The viral lipid envelope originates from the host cell’s membrane and is thus not affected by natural viral diversity and variability [ 26 ].…”

SARS-CoV-2 inhibitory activity of a short peptide derived from internal fusion peptide of S2 subunit of spike glycoprotein

“…The localization of our PN19 peptide and its ability to bind MPER derived peptide could indicate a different mechanism of inhibitory activity. Molecular evidence showed that juxtaposition of the S2 IFP and MPER domains facilitates the formation of the fusion pore through lipid destabilization in the late steps of viral cell membrane fusion ( Behzadipour and Hemmati, 2022 ; Palombi et al., 2021 ; Santamaria et al., 2022 ; Mahajan and Bhattacharjya, 2015 ). Thus, the interaction between the IFP and the MPER in membrane context would be one of the most important targets where peptide PN19 exerted its mechanism of action.…”

DEAD-Box Helicase DDX3X as a Host Target against Emerging Viruses: New Insights for Medicinal Chemical Approaches

“…On the contrary, indirect-acting antivirals (IAAs) inhibit the host’s proteins, with the advantage of reducing the viral resistance associated with viral high mutation rates . A large number of host proteins are implicated in viral replication for entry, genome replication, and host immune signaling . DEAD-box helicases are a large family of human proteins involved in cell cycle control, immune system, and all aspects of RNA metabolism, including ribosome biogenesis, translation, and decay .…”

“…On the contrary, human proteins possess DNA-repair enzymes able to minimize the number of mutations. Accordingly, some host directed antivirals (HDAs) have been designed in recent years, targeting human proteins involved in immune signaling pathways or in viral replication processes like translation or cell traffic . A successful example on this regard is represented by maraviroc which binds human chemokine receptor CCR5, preventing HIV-1 entry.…”

“…3 A large number of host proteins are implicated in viral replication for entry, genome replication, and host immune signaling. 4 DEAD-box helicases are a large family of human proteins involved in cell cycle control, immune system, and all aspects of RNA metabolism, including ribosome biogenesis, translation, and decay. 5 Among them, the protein DDX3X was extensively studied for its implication in RNA metabolism, innate immune signaling, and cell cycle regulation.…”