Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity.
Proc Natl Acad Sci U S A
; 117(41): 25759-25770, 2020 10 13.
Article
in English
| MEDLINE | ID: covidwho-807358
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Human coronaviruses OC43 and HKU1 are respiratory pathogens of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spillover. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S with hemagglutinin-esterase (HE) acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity toward clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations led to cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and coevolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein species, is unique among CoVs, but reminiscent of that of influenza A viruses. Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virion
/
Viral Fusion Proteins
/
Coronavirus
/
Spike Glycoprotein, Coronavirus
/
Hemagglutinins, Viral
Type of study:
Experimental Studies
/
Randomized controlled trials
Topics:
Variants
Language:
English
Journal:
Proc Natl Acad Sci U S A
Year:
2020
Document Type:
Article
Affiliation country:
Pnas.2006299117
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