OC43 clinical isolate spike proteins have distinct carbohydrate-binding properties

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Human coronavirus OC43 (OC43) is a common cause of colds.
• Tissue culture-adapted OC43 strains are widely used but may not accurately model clinical isolates.
• Differences in entry mechanisms and hemagglutinin-esterase (HE) activity exist between OC43 strains.

Purpose of the Study:

• To investigate differences in carbohydrate-binding properties of spike proteins from OC43 clinical isolates compared to a lab-adapted strain.
• To understand the structural basis for altered receptor binding and identify determinants of specificity differences.

Main Methods:

• Comparative analysis of spike protein carbohydrate-binding properties.
• Structural analysis of OC43 clinical isolate spike protein.
• Investigation of mucin binding and interaction with sialic acid moieties.

Main Results:

• OC43 clinical isolates exhibit distinct carbohydrate-binding properties compared to the lab-adapted OC43-Lab strain.
• Spike proteins of clinical isolates possess unique inserts near the carbohydrate-binding site, influencing specificity.
• Unlike HCoV-HKU1, OC43 clinical isolates do not bind with high affinity to the 9-O-acetylated α2-8-linked disialic acid moiety.

Conclusions:

• Structural differences, particularly insert-2, in OC43 clinical isolate spike proteins dictate altered binding specificity.
• These findings suggest common adaptation mechanisms for coronaviruses like OC43 and HKU1 to the human sialoglycome.
• Lab-adapted OC43 strains may not fully represent the biological behavior of clinical OC43 isolates.