Class I fusion protein biosynthesis and inhibition

HIV-1, influenza virus, Ebola virus, and SARS-CoV-2 produce class I fusion proteins to infect cells. The core structure of class I fusion proteins features trimeric hairpins with a central coiled-coil structure, which are produced from their polypeptide precursors after cleavage by furin. During this process, class I fusion proteins are targeted by different types of host factors. Currently, we are investigating how ER chaperones (calnexin, calreticulin, PDIA3) and class I α-mannosidases (such as MAN1B1) trigger class I fusion protein degradation via reticulophagy. In addition, we are investigating how MARCHF E3 ubiquitin ligases inhibit furin to block their maturation. Moreover, we are investigating how SERINC5 inactivates them and how SERINC5 is counteracted by HIV-1 Nef, MLV glycoGag, and EIAV S2 proteins. On the other hand, we are also investigating in addition to ACE2, TMPRSS2, and CTSL, how SARS-CoV-2 enters cells via Niemann-Pick C1 (NPC1) known as the Ebola virus receptor. These investigations will lead to broad antiviral mechanisms to inhibit these highly pathogenic human viruses.