SARS-CoV-2 spike protein (S) (S protein)

The SARS-CoV-2 spike protein (S) is a large, trimeric class I fusion glycoprotein that projects from the surface of the virus and is essential for its entry into host cells [3, 4]. It is functionally divided into two subunits: the S1 subunit, which contains the receptor-binding domain (RBD) for attachment to the human angiotensin-converting enzyme 2 (ACE2) receptor, and the S2 subunit, which undergoes significant conformational changes to facilitate the fusion of the viral and host cell membranes [2, 12, 14]. As the primary target for neutralizing antibodies produced during infection or vaccination, the spike protein is the central focus for the development of COVID-19 vaccines and monoclonal antibody therapies [5, 9, 13]. Drugs targeting this protein typically work by sterically blocking the RBD-ACE2 interface or preventing the structural rearrangements in S2 required for viral entry [4, 5, 9]. However, the protein's high mutation rate has led to the emergence of variants of concern, such as Delta and Omicron, which can partially evade immune responses and reduce the efficacy of established treatments [16, 17].

Other names

Spike glycoproteinS glycoproteinSurface glycoproteinSpike protein2019-nCoV spike protein

Drugs and vaccines targeting the spike protein work by neutralizing the viral entry process; specifically, they either sterically hinder the Receptor Binding Domain (RBD) from interacting with the human ACE2 receptor or prevent the structural rearrangements in the S2 subunit required for viral-host membrane fusion [2, 4, 5, 9].