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Publications of the Week

Structural Basis for Human Coronavirus Attachment to Sialic Acid Receptors

By June 19, 2019June 21st, 2019No Comments

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This week we profile a recent publication in Nature Structural & Molecular Biology
from the laboratory of Dr. David Veesler (pictured, fifth from left) at UW.

Can you provide a brief overview of your lab’s current research focus?

My lab works toward preventing and/or curing infectious diseases, many of which disproportionally affect developing countries. My main research interest is to understand viral pathogenesis using an integrative approach to obtain multi-scale data ranging from atom to whole-cell. We leverage our understanding of the molecular architecture of pathogens, resulting from our structural biology efforts, to guide the design of vaccines and therapeutics.

What is the significance of the findings in this publication?

Coronaviruses have caused outbreaks of deadly pneumonia in humans since the beginning of the 21st century. The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and was responsible for an epidemic that spread to five continents with a fatality rate of 10% before being contained in 2003 (with additional cases reported in 2004). The Middle-East respiratory syndrome coronavirus (MERS-CoV) emerged in the Arabian Peninsula in 2012 and has caused recurrent outbreaks in humans with a fatality rate of 35%. SARS-CoV and MERS-CoV are zoonotic viruses that crossed the species barrier using bats/palm civets and dromedary camels, respectively. Four other coronaviruses of zoonotic origin are endemic in the human population, accounting for up to 30% of mild respiratory tract infections and also causing severe complications or fatalities in young children, the elderly or immunocompromised individuals. These viruses are HCoV-NL63 and HCoV-229E as well as HCoV-OC43 and HCoV-HKU1. Currently, no specific antiviral treatments or vaccines are available to combat any human coronavirus. Studying coronaviruses will therefore help in understanding the principles governing cross-species transmission and adaptation to humans as well as in preparing for putative future zoonotic outbreaks.

What are the next steps for this research?

In this manuscript, (i) we report the first coronavirus spike glycoprotein structure in complex with a saccharide, providing an atomic description of the interactions involved in attachment to sialoside receptors at the host cell surface (ii) we demonstrate sialic acid binding at the site identified is required for viral infection, thereby providing a blueprint to guide the design of inhibitors of viral entry, (iii) we provide the first atomic-level description of the spike glycoprotein of HCoV-OC43, which is the most prevalent coronavirus in the human population and a cause of children hospitalization.

This work was funded by:

Research reported in this publication was supported by the National Institute of General Medical Sciences (R01GM120553), a Pew Biomedical Scholars Award and an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund.

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