SARS-CoV-2 Spike Glycoprotein Targets ACE2 in Humans

The interactions between SARS-CoV-2's spike transmembrane glycoprotein and human angiotensin-converting enzyme 2 (ACE2) are paramount for the Coronavirus Disease 2019 (COVID-19). Specific amino acid sequences in the receptor-binding domain of the spike protein are particularly significant for binding to the ACE2 receptor. Another central domain of the spike protein is the fusion domain. The fusion domain is accessible following host-dependent catalytic cleavage of the receptor-binding domain. The hydrophobic fusion portion is specifically responsible for facilitating the fusion events between the viral lipid envelope and the host cell's plasma membrane. ACE2 is a mammalian transmembrane protein that serves as a binding partner for the spike protein and participates in cardioprotective effects by regulating the renin-angiotensin-aldosterone system. The ACE2 receptor is expressed in various human tissues and provides a rationale for the transmissibility efficiency of the COVID-19 virus. Moreover, the concentration and structural organization of ACE2 in the human population explains the range of clinical symptoms and disease outcomes observed during the pandemic. Further investigation of the spike protein and ACE2 receptor may fuel innovative biological technologies to limit spike-ACE2 interaction to reduce SARS-CoV-2 infections and expand therapeutics to curb post-infection disease progression.