COVID-19: insights into virus-receptor interactions

Abstract

The recent outbreak of Coronavirus Disease 2019 (COVID-19) calls for rapid mobilization of scientists to probe and explore solutions to this deadly disease. A limited understanding of the high transmissibility of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) relative to other coronavirus strains guides a deeper investigation into the virus/receptor interactions. The cutting-edge studies in thermodynamic and kinetic properties of interactions such as protein-protein interplays have been reviewed in many modeling and analysis studies. Highlighting the thermodynamic assessments of biological interactions and emphasizing the boosted transmissibility of SARS-CoV-2 despite its high similarity in structure and sequence with other coronavirus strains is an important and highly valuable investigation that can lead scientists to discover analytical and fundamental approaches in studying virus's interactions. Accordingly, we have attempted to describe the crucial factors such as conformational changes and hydrophobicity particularities that influence on thermodynamic potentials in the SARS-COV-2 S-protein adsorption process. Discussing the thermodynamic potentials and the kinetics of the SARS-CoV-2 S-protein in its interaction with the ACE2 receptors of the host cell is a fundamental approach that would be extremely valuable in designing candidate pharmaceutical agents or exploring alternative treatments.

Keywords: ACE2; COVID-19; Conformational changes; Coronavirus; Glycosylation; Hydrophobicity; SARS-CoV-2; Thermodynamics; Virus-cell interactions.

Fig. 1

Cartoon representation of the interaction between SARS-CoV-2 S-protein RBD and ACE2. Positions and names of the hot spot residues of the SARS-CoV-2 S-protein RBD/ACE2 are shown. The hydrogen bonds between intra-protein residues are shown by yellow dotted line. The Protein Data Bank (PDB) code for SARS-CoV-2 S-protein is 6VXX, PDB code for RBD region is 7C01 and PDB code for ACE2 is 1R42

Fig. 2

The changes in enthalpy of the SARS-CoV-2/ACE2 host cell system on the association. H1 represents the total reacting amino acids bond energy by adding RBD amino acid binding energies (E1) to ACE2 amino acid binding energies (E2). H2 represents the total reacted amino acids bond energy by adding binding energy of each RBD amino acid to ACE2 amino acid (e1 + e2 + … = Ʃe). Negative values of ΔH indicate the higher potential binding energy level of reacting amino acids (H1 > H2)

Fig. 3

Compering the sequence differences between SARS-CoV-2 and SARS-CoV S-protein RBD regions. Red sequon represented the potential in vivo glycosylation sites, green residues represented the place of hydrogen bonds, and blue residues participating in the salt-bridge. The two important sequon were colored in orange with their GRAVY number. GenBank accession numbers QHR63250.1 (SARS-CoV-2 S), AY278488.2 (SARS-CoV S)