Abstract
Coronaviruses are responsible for several epidemics, including the 2002 SARS, 2012 MERS, and COVID-19. The emergence of recent COVID-19 pandemic due to SARS-CoV-2 virus in December 2019 has resulted in considerable research efforts to design antiviral drugs and other therapeutics against coronaviruses. In this context, it is crucial to understand the biophysical and structural features of the major proteins that are involved in virus-host interactions. In the current study, we have compared spike proteins from three strains of coronaviruses NL63, SARS-CoV, and SARS-CoV, known to bind human angiotensin-converting enzyme 2 (ACE2), in terms of sequence/structure conservation, hydrophobic cluster formation and importance of binding site residues. The study reveals that the severity of coronavirus strains correlates positively with the interaction area, surrounding hydrophobicity and interaction energy and inversely correlate with the flexibility of the binding interface. Also, we identify the conserved residues in the binding interface of spike proteins in all three strains. The systematic point mutations show that these conserved residues in the respective strains are evolutionarily favored at their respective positions. The similarities and differences in the spike proteins of the three viruses indicated in this study may help researchers to deeply understand the structural behavior, binding site properties and etiology of ACE2 binding, accelerating the screening of potential lead molecules and the development/repurposing of therapeutic drugs.
Keywords: ACE2 binding; COVID-19; NL63; SARS; coronavirus spike protein; mutational analysis; surrounding hydrophobicity.
【저자키워드】 COVID-19, SARS, NL63, coronavirus spike protein, mutational analysis, ACE2 binding, surrounding hydrophobicity., 【초록키워드】 ACE2, Coronaviruses, coronavirus, SARS-CoV, COVID-19 pandemic, severity, antiviral drugs, Epidemics, drugs, SARS-CoV-2 virus, MERS, virus, Spike protein, antiviral drug, binding site, Protein, Virus-host interactions, therapeutic, Research, Cluster, hydrophobicity, NL63, coronavirus spike protein, etiology, Strains, binding, flexibility, Human angiotensin-converting enzyme 2, Angiotensin-converting enzyme, Interaction, angiotensin, Point mutation, Spike proteins, ACE2 binding, strain, similarity, enzyme, residue, human Angiotensin-converting enzyme, help, effort, similarities, residues, hydrophobic, coronavirus strains, researcher, feature, responsible, identify, conserved, involved, indicated, coronavirus strain, the spike protein, reveal, 【제목키워드】 coronavirus strain,