COVID-19 Spike-host cell receptor GRP78 binding site prediction

Abstract

Abstract Coronaviruses have been circulating between animals and humans repeatedly. A novel human coronavirus, named COVID-19, has recently emerged in Hubei Province, China. Within the first two months, more than 2200 deaths have been confirmed, and there have been more than 79,000 hospitalized patients, mainly in China. Understanding the virus mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition. In this study, the COVID-19 corona viral spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The cyclic peptide Pep42 (CTVALPGGYVRVC) was reported earlier to be the docking platform of GRP78 in cancer cells. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Sequence and structural alignments show that four regions, in addition to its cyclic nature (the S-S bond), have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor. We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues (region IV) of the spike can be used to develop therapeutics specific against COVID-19.