E3 ubiquitin ligases modulate SARS-CoV-2 replication and immune evasion through targeted protein degradation mechanismsSARS-CoV-2 uses host enzymes to hide from the immune system

Following the global outbreak of the COVID-19 pandemic, the interactions between SARS-CoV-2 and host cells have attracted widespread attention. As crucial intracellular enzymes, E3 ubiquitin ligases are involved in numerous physiological processes, including protein degradation, cell cycle regulation, and immune responses. Recent studies have demonstrated that E3 ubiquitin ligases play a pivotal role in the interplay between SARS-CoV-2 and the host. Through interactions with host E3 enzymes, SARS-CoV-2 regulates key processes such as viral replication, immune evasion, and apoptosis. For instance, viral proteins can bind to E3 enzymes to modulate host immune responses and inhibit interferon production, thereby promoting persistent infection. Conversely, E3 enzymes can also regulate the viral life cycle and host cell survival by mediating targeted protein degradation. This mini-review summarizes the roles of E3 ubiquitin ligases in SARS-CoV-2 infection, introduces E3 ligase-mediated ubiquitin-like modifications, and discusses their underlying mechanisms at the virus-host interface. Furthermore, we highlight future research directions and potential therapeutic strategies. Understanding the functions of E3 ubiquitin ligases not only provides novel insights into the pathogenesis of SARS-CoV-2 but also offers promising targets for the development of antiviral therapeutics.