Abstract

Betacoronaviruses, responsible for the “Severe Acute Respiratory Syndrome” (SARS) and the “Middle East Respiratory Syndrome” (MERS), use the spikes protruding from the virion envelope to attach and subsequently infect the host cells. The coronavirus spike (S) proteins contain receptor binding domains (RBD), allowing the specific recognition of either the dipeptidyl peptidase CD23 (MERS-CoV) or the angiotensin-converting enzyme ACE2 (SARS-Cov, SARS-CoV-2) host cell receptors. The heavily glycosylated S protein includes both complex and high-mannose type N-glycans that are well exposed at the surface of the spikes. A detailed analysis of the carbohydrate-binding specificity of mannose-binding lectins from plants, algae, fungi, and bacteria, revealed that, depending on their origin, they preferentially recognize either complex type N-glycans, or high-mannose type N-glycans. Since both complex and high-mannose glycans substantially decorate the S proteins, mannose-specific lectins are potentially useful glycan probes for targeting the SARS-CoV, MERS-CoV, and SARS-CoV-2 virions. Mannose-binding legume lectins, like pea lectin, and monocot mannose-binding lectins, like snowdrop lectin or the algal lectin griffithsin, which specifically recognize complex N-glycans and high-mannose glycans, respectively, are particularly adapted for targeting coronaviruses. The biomedical prospects of targeting coronaviruses with mannose-specific lectins are wide-ranging including detection, immobilization, prevention, and control of coronavirus infection.

Highlights

  • Depending on the differences observed in the fine specificity towards complex glycans, high-mannose glycans, and hybrid glycans, Man-specific lectins from diverse origins can be used as glycan probes for targeting diverse types of N-glycans covering both host cell and viral surfaces

  • Depending on the coronaviruses, some discrepancies occur between the distribution of the two types of glycans on the surface of the virion, which introduces some diversity in the glycan shield covering the coronavirus spikes [11]

  • GNA-related lectins together with Man-specific lectins from algae and cyanobacteria, appear as glycan probes nicely adapted to the recognition of the high-mannose shield which predominates at the top of the MERS-CoV spike

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Summary

Introduction

As shown for plant lectins, the differences observed in the specific recognition of Man-containing glycans, essentially depend on both the axial position of the hydroxyl group at C2 in Man which is more or less strictly recognized by the carbohydratebinding sites (CBSs) of lectins, and the type of glycosidic bonds α1,2, α1,3 or α1,6, and their internal or external position in the glycan chain, recognized by lectins [23] According to these discrepancies and with respect to the diversity of N-glycans occurring at the surface of the coronavirus spikes, many distinct Man-specific lectins from plants, algae, fungi, and bacteria, could serve as relevant glycan probes for SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses. They belong to quite different structural scaffolds [20], all of these lectins contain CBSs that display a more or less strict specificity for mannose (Man) and Mancontaining glycoproteins

Man-Specific Lectins from Higher Plants
Man-Specific Lectins from Lower Plants and Fungi
Man-Specific Lectins from Algae and Bacteria
Biomedical Perspectives
Bioinformatics
Findings
Discussion

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