SARS-CoV-2 spike protein S2 subunit heptad repeat 2 region (HR2)

The SARS-CoV-2 spike protein S2 subunit heptad repeat 2 (HR2) region is a critical structural component of the viral fusion machinery. It plays a pivotal role in the transition of the spike protein from a pre-fusion to a post-fusion state, a process necessary for the virus to deliver its genetic material into the host cell (UniProt P0DTC2). Specifically, the HR2 region folds back to interact with the heptad repeat 1 (HR1) region, forming a six-helix bundle (6-HB) that drives the fusion of the viral envelope with the host cell membrane (Xia et al., 2020, Cell Research). This fusion process is a key target for antiviral drug development, as blocking 6-HB formation effectively prevents infection. Therapeutic strategies often involve HR2-derived peptides, such as EK1 and its derivatives, which act as decoys by binding to HR1 and preventing the endogenous HR2 from completing the fusion core (Xia et al., 2019, Science Advances). Due to the high conservation of the HR2 sequence among coronaviruses, it is considered a high-priority target for pan-coronavirus inhibitors (Zhu et al., 2020, Nature Communications).

Other names

Heptad repeat 2HR2 domainS2-HR2Spike protein HR2 region

Fusion inhibition; HR2-derived peptides or small molecules prevent the formation of the six-helix bundle (6-HB) by blocking the interaction between the HR1 and HR2 regions of the S2 subunit.