5.1 Blocking the combination of S protein and ACE2
Alanine scanning mutagenesis analysis was performed to identify determinants on ACE2 critical for SARS-CoV infection. The researchers found that charged amino acids between residues 22 and 57 were important, K26 and D30, in particular(Han et al. , 2006). At the meanwhile, Matthew found that a novel ACE2 inhibitor, NAAE, is effective in blocking the SARS coronavirus spike protein-mediated cell fusion by a structure-based approach(Huentelman et al. , 2004). Based on the combination of S protein and ACE2 in COVID-19, the structures of full-length human ACE2 have been revealed for the first time, and the dimeric ACE2 can accommodate two S protein trimers in SARS-CoV-2(Yanet al. , 2020). After the discovery of structures of full-length human ACE2, one study has determined the key region in SARS-CoV-2 that is responsible for the interaction with human ACE2(Wang et al. , 2020). Moreover, Shang and his colleague confirmed that a four-residue motif (residues 482-485: Gly-Val-Glu-Gly) could change the interface of SARS-CoV-2 RBM and ACE2, which may provide a potential target for intervention strategies(Shang et al. , 2020). According to these discoveries, researchers determined the Mpro and RdRp were the mainly target of infection by analyzing the RNA polymerase(Gao et al. , 2020; Jin et al. , 2020). Although it is the most fundamental method to block the combination of ACE2 and SARS-CoV, this method is time-consuming and costly. Meanwhile, it is difficult to predict the variation of coronavirus.