A Carbohydrate-Binding Protein from the Edible Lablab Beans Effectively Blocks the Infections of Influenza Viruses and SARS-CoV-2

Abstract

Summary The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans ( Lablab purpureus ), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19.

Sensing the interactions between carbohydrate-binding agents and N-linked glycans of SARS-CoV-2 spike glycoprotein using molecular docking and simulation studies

“…The binding study of DLL-I with recombinant S glycoprotein displays strong affinity and interaction with complex type N-glycans as compared to high-Mannose type N-glycans. This new report and previous studies of lectins from various sources against CoVs strengthen their potential to be used as antivirals (Liu et al, 2020). A recent docking analysis and simulation study predicted the probable binding site of the ACE2 receptor with the RBD of S glycoprotein wherein the Asn343 lies in close proximity of the predicted intermolecular glycan-glycan interactions between Asn74, Asn165 of S glycoprotein and Ans546 of ACE2 receptor.…”

Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience

“…In influenza, the two major internal proteins hemagglutinin (HA) and neuraminidase (NA) mediate virus entry whereas in COVID-19 the spike (S) protein is the leading mediator of virus entry and is a primary determinant of cell tropism and pathogenesis. HA and S proteins are both heavily glycosylated which could make them susceptible to similar components of innate and adaptive immunity (60). Further explanation for a protective effect of the flu vaccine could be that the vaccine for H1N1 seems to have a protective effect on other viruses such as H3N2, thanks to a protective cross-response mediated by Toll Like Receptors through MHC II molecules such as DRB1*04:01 (27).…”

The ACE2-binding Interface of SARS-CoV-2 Spike Inherently Deflects Immune Recognition

“…One possible explanation for the minimal immunogenicity of the ACE2IS is its conformational flexibility. Although the ACE2IS is well defined when bound to ACE2 or to an antibody, it is disordered in the free spike structures ( Figure 4 (B)), 1 , 2 , 4 , 27 , 28 , 29 , 30 suggesting that the ACE2IS is inherently flexible. It is difficult to generate antibodies to a flexible region, due to a large loss of conformational entropy upon binding that disfavors binding.…”