COVID-19 novel coronavirus (CoV) disease caused by severe acquired respiratory syndrome (SARS)-CoV-2 manifests severe lethal respiratory illness in humans and has recently developed into a worldwide pandemic. The lack of effective treatment strategy and vaccines against the SARS-CoV-2 poses a threat to human health. An extremely high infection rate and multi-organ secondary infection within a short period of time makes this virus more deadly and challenging for therapeutic interventions. Despite high sequence similarity and utilization of common host-cell receptor, human angiotensin-converting enzyme-2 (ACE2) for virus entry, SARS-CoV-2 is much more infectious than SARS-CoV. Structure-based sequence comparison of the N-terminal domain (NTD) of the spike protein of Middle East respiratory syndrome (MERS)-CoV, SARS-CoV, and SARS-CoV-2 illustrate three divergent loop regions in SARS-CoV-2, which is reminiscent of MERS-CoV sialoside binding pockets. Comparative binding analysis with host sialosides revealed conformational flexibility of SARS-CoV-2 divergent loop regions to accommodate diverse glycan-rich sialosides. These key differences with SARS-CoV and similarity with MERS-CoV suggest an evolutionary adaptation of SARS-CoV-2 spike glycoprotein reciprocal interaction with host surface sialosides to infect host cells with wide tissue tropism.
【저자키워드】 SARS-CoV-2, spike glycoprotein, MERS-CoV, N-terminal domain, 【초록키워드】 COVID-19, Treatment, ACE2, Vaccine, SARS-CoV, Human, Infection, Respiratory illness, virus, Novel coronavirus, Region, Health, SARS-CoV-2 spike glycoprotein, virus entry, CoV, NTD, receptor, infection rate, angiotensin-converting enzyme-2, disease, binding, Interaction, Analysis, similarity, Middle East, host cell, tissue tropism, Comparative, worldwide pandemic, sequence, syndrome, therapeutic interventions, sequence similarity, conformational flexibility, infect, Host, effective, binding pockets, lack, caused, the spike protein, the SARS-CoV-2, 【제목키워드】 spike, pocket,