COVID-19 pandemic: Insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a newly emerging, highly transmissible, and pathogenic coronavirus in humans that has caused global public health emergencies and economic crises. To date, millions of infections and thousands of deaths have been reported worldwide, and...

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Bibliographic Details
Published in:	PLoS pathogens 2020-08, Vol.16 (8), p.e1008762
Main Authors:	Mittal, Anshumali, Manjunath, Kavyashree, Ranjan, Rajesh Kumar, Kaushik, Sandeep, Kumar, Sujeet, Verma, Vikash
Format:	Article
Language:	eng
Subjects:	ACE2 Angiotensin Angiotensin converting enzyme Angiotensin-Converting Enzyme 2 Animals Antigenicity Betacoronavirus - pathogenicity Binding Biology and life sciences Cell fusion Cell membranes Comparative analysis Coronaviridae Coronavirus Infections - metabolism Coronavirus Infections - virology Coronaviruses COVID-19 Disease transmission DNA-directed RNA polymerase Economic crisis Fusion protein Genetic aspects Glycoproteins Health aspects Host range Humans Infections Medicine and health sciences Membrane fusion Middle East respiratory syndrome Observations Pandemics Peptidyl-dipeptidase A Peptidyl-Dipeptidase A - metabolism Pneumonia, Viral - metabolism Pneumonia, Viral - virology Protein binding Proteins Public health Receptors Receptors, Virus - immunology Receptors, Virus - metabolism Recognition Respiratory diseases Review RNA-directed RNA polymerase SARS-CoV-2 Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - immunology Spike Glycoprotein, Coronavirus - metabolism Structure-function relationships Vaccines Viral diseases Viral proteins Virulence (Microbiology) Virus Internalization Viruses
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Summary:	Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a newly emerging, highly transmissible, and pathogenic coronavirus in humans that has caused global public health emergencies and economic crises. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism(s) through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor-binding domain (RBD) of the spike (S) glycoprotein to recognize angiotensin-converting enzyme 2 (ACE2) receptors on the human cells; this initiates host-cell entry by promoting viral-host cell membrane fusion through large-scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the structure of RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and its significance in drug discovery and explain the receptor recognition mechanisms of coronaviruses. Further, we provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins and their receptor-binding specificity and discuss the differences in their antigenicity based on biophysical and structural characteristics.
ISSN:	1553-7374 1553-7366 1553-7374