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1.
Frontiers in microbiology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1837950

ABSTRACT

Canine coronavirus (CCoV) and feline coronavirus (FCoV) are endemic in companion animals. Due to their high mutation rates and tendencies of genome recombination, they pose potential threats to public health. The molecular characteristics and genetic variation of both CCoV and FCoV have been thoroughly studied, but their origin and evolutionary dynamics still require further assessment. In the present study, we applied a comprehensive approach and analyzed the S, M, and N genes of different CCoV/FCoV isolates. Discriminant analysis of principal components (DAPC) and phylogenetic analysis showed that the FCoV sequences from Chinese isolates were closely related to the FCoV clusters in Netherlands, while recombination analysis indicated that of S N-terminal domain (NTD) was the most susceptible region of mutation, and recombination of this region is an important cause of the emergence of new lineages. Natural selection showed that CCoV and FCoV subgenotypes were in selection constraints, and CCoV-IIb was in strong positive selection. Phylodynamics showed that the mean evolution rate of S1 genes of CCoV and FCoV was 1.281 × 10–3 and 1.244 × 10–3 subs/site/year, respectively, and the tMRCA of CCoV and FCoV was about 1901 and 1822, respectively. Taken together, our study centered on tracing the origin of CCoV/FCoV and provided ample insights into the phylogeny and evolution of canine and feline coronaviruses.

2.
ACS Infect Dis ; 8(5): 1041-1050, 2022 05 13.
Article in English | MEDLINE | ID: covidwho-1788265

ABSTRACT

A panel of O-acetylated N-glycolylneuraminic acid oligosaccharides has been prepared by diversification of common synthetic precursors by regioselective de-O-acetylation by coronaviral hemagglutinin-esterase (HE) combined with C7-to-C9 acetyl ester migration. The resulting compound library was printed on streptavidin-coated glass slides to give a microarray to investigate receptor binding specificities of viral envelope glycoproteins, including spike proteins and HEs from animal and human coronaviruses. It was found that the binding patterns of the viral proteins for N-glycolylated sialosides differ considerable from those of the previously synthesized N-acetylated counterparts. Generally, the spike proteins tolerate N-glycolyl modification, but selectivities differ among viruses targeting different hosts. On the other hand, the lectin domain of the corresponding HEs showed a substantial decrease or loss of binding of N-glycolylated sialosides. MD simulations indicate that glycolyl recognition by HE is mediated by polar residues in a loop region (109-119) that interacts with the 5-N-glycolyl moiety. Collectively, the results indicate that coronaviruses have adjusted their receptor fine specificities to adapt to the sialoglycome of their host species.


Subject(s)
Coronavirus Infections , Coronavirus , Animals , Glycoproteins , Neuraminic Acids , Oligosaccharides , Spike Glycoprotein, Coronavirus
3.
Nat Chem ; 13(5): 496-503, 2021 05.
Article in English | MEDLINE | ID: covidwho-1145994

ABSTRACT

The transmission of viruses from animal reservoirs to humans poses major threats to public health. Preparedness for future zoonotic outbreaks requires a fundamental understanding of how viruses of animal origin have adapted to binding to a cell surface component and/or receptor of the new host. Here we report on the specificities of human and animal viruses that engage with O-acetylated sialic acid, which include betacoronaviruses, toroviruses and influenza C and D viruses. Key to these studies was the development of a chemoenzymatic methodology that can provide almost any sialate-acetylation pattern. A collection of O-acetylated sialoglycans was printed as a microarray for the determination of receptor specificity. These studies showed host-specific patterns of receptor recognition and revealed that three distinct human respiratory viruses uniquely bind 9-O-acetylated α2,8-linked disialoside. Immunofluorescence and cell entry studies support that such a glycotope as part of a ganglioside is a functional receptor for human coronaviruses.


Subject(s)
N-Acetylneuraminic Acid/chemistry , Respiratory Tract Infections/virology , Viruses/pathogenicity , Humans , Transfection
4.
Proc Natl Acad Sci U S A ; 117(41): 25759-25770, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-807358

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.


Subject(s)
Coronavirus/physiology , Hemagglutinins, Viral/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Fusion Proteins/genetics , Virion/metabolism , Animals , Biological Evolution , Cell Line , Coronavirus/genetics , Coronavirus/metabolism , Coronavirus Infections/virology , Coronavirus OC43, Human/genetics , Coronavirus OC43, Human/metabolism , Coronavirus OC43, Human/physiology , Coronavirus, Bovine/genetics , Coronavirus, Bovine/metabolism , Coronavirus, Bovine/physiology , Hemagglutinins, Viral/chemistry , Hemagglutinins, Viral/metabolism , Humans , Lectins/genetics , Lectins/metabolism , Mice , Mutation , Protein Binding , Protein Domains , Receptors, Virus/metabolism , Selection, Genetic , Sialic Acids/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Viral Fusion Proteins/chemistry , Viral Fusion Proteins/metabolism , Virion/genetics , Virus Attachment , Virus Release
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