A Review of Human Coronaviruses' Receptors: The Host-Cell Targets for the Crown Bearing Viruses

Abstract

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.

Keywords: COVID-19; SARS-CoV-2; cell receptor; human coronavirus; spike; viral entry.

Figure 1

The structure of the SARS-CoV-2 spike protein (PDB ID: 6VXX). The monomeric spike is shown as a cartoon colored by its different domains from its N-terminus to the C-terminus. The spike protein is mono-trimeric, forming a crown-like structure over the virion.

Figure 2

(A) Human aminopeptidase N (APN): different parts and the binding site with HCoV-229E (PDB ID: 5LHD). Blue: tail (62–281), pink: body (282–543), orange: side (544–632), green: body (633–693), and yellow: binding site of HCoV-229E (283–292). A Zn⁺² ion is in the middle. (B) A monomer of the postfusion core structure of HCoV-229E (top). HR1 (green cartoon) consists of 24 alpha helices. HR2 (cyan cartoon) contains two conformations, including 9 alpha helices (from amino acid 1067 to amino acid 1098) and extended conformation in both cases. The postfusion core (trimer) structure of HCoV-229E (bottom) is shown from side and top views with 90° rotation angle.

Figure 3

The critical inhibitory role of integrin in SARS-CoV-2.