Cellular signalling by SARS-CoV-2 spike protein

Following the release of the SARS-CoV-2 genome, the spike protein was identified as the key viral protein mediating cell entry. In addition to its critical function in delivering the viral genome to the host cytoplasm, the spike protein is able to activate diverse cell signalling pathways, leading to notable cellular responses, including inflammation, cellular remodelling, and immune evasion. The spike protein is associated with the induction of a 'cytokine storm' characterised by elevated levels of proinflammatory cytokines like IL-6 and IL-1 beta. Moreover, the spike protein deregulates TGF-beta and E-selectin, leading to fibrotic injury and tissue scarring in cellular remodelling, notably in pulmonary tissues. Finally, the spike protein plays a role in immune evasion, disrupting Type I interferon responses. Understanding these diverse interactions and effects is crucial for comprehending the pathogenesis of COVID-19 and developing effective therapeutic strategies.