Identification Small Molecules Inhibit the SARS-Cov-2 Spike-ACE2 (PPI) |Biomedgrid

Acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for COVID-19 which reached pandemic levels in early 2020 (WHO; March 11, 2020) [1,2]. There are three types of CoVs that reached pandemic levels in the last twenty years: SARS-CoV-1, MERS-CoV and SARS-CoV-2 [3]. Coronaviruses use the Receptor- Binding Domain (RBD) of the homotrimeric spike (s) glycoprotein emerging from its surface of the envelope to bind to their cellular receptors [4]. This binding facilitates a cascade of events that leads to the penetration host cell and finally the virus replication [5]. Binding to the Angiotensin-Converting Enzyme-2 (ACE2) receptor is a key consideration step for entering SARS-CoV into target cells [6-9]. The Protein-Protein Interaction [10] (PPI) between the SARS-CoV-2 spike protein and Human ACE2 (hACE2) (Figure1), in the early stages of the life cycle created a significant therapeutic need for possible antiviral drug development. The current SARSCoV antibodies are not effective in case SARS-CoV-2 [11]. All protein therapies showed great problems such as solubility, unsuitability for oral or inhaled administration, and immunogenicity. In addition, being foreign proteins in nature work as antigens and elicit strong immune responses in certain patients [12].