Severe acute respiratory syndrome coronavirus 2 spike protein heptad repeat domain (SARS-CoV-2 S-HR)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein heptad repeat (HR) domain is a critical component of the S2 subunit responsible for viral-host cell membrane fusion (UniProt P0DTC2). It consists of two distinct regions, heptad repeat 1 (HR1) and heptad repeat 2 (HR2), which undergo a dramatic conformational change following the binding of the S1 subunit to the ACE2 receptor and subsequent proteolytic priming (PubMed 32275855). During this process, HR1 and HR2 interact to form a stable six-helix bundle (6-HB) fusion core, which brings the viral envelope and the host cell membrane into close proximity to facilitate fusion and viral entry (PubMed 32231345). Because this mechanism is essential for infection and is relatively conserved across coronavirus variants, the HR domain serves as a high-priority therapeutic target (PubMed 32348330). Drugs targeting this domain, primarily fusion-inhibitory peptides like EK1 and its derivatives, work by binding to the HR1 grooves and preventing the assembly of the 6-HB (PubMed 32275855). This intervention effectively blocks the entry of the virus into the host cell, offering a strategy for both prophylaxis and treatment of COVID-19.

Other names

Heptad repeat 1Heptad repeat 2HR1HR2S2 subunit heptad repeatSARS-CoV-2 S2 heptad repeat

Fusion inhibition by competitively binding to the HR1 or HR2 domains to prevent the formation of the six-helix bundle (6-HB) required for viral-cell membrane fusion (PubMed 32275855).