Betacoronaviral lectins: Identification through a genomic search—A structural and evolutionary biology perspective

Abstract

Carbohydrate-binding proteins known as “Lectins” play a crucial role in host-pathogen interactions. Most of the viral surface proteins have lectin activity. In fact, they make the first line of communication with the host cells. Recent reports indicating the haemagglutination property and structural evidences of coronaviral protein bound with Sialic acid (Sia) draw our attention to exploring the presence of lectins in the Betacoronavirus genus from reference genomes. We have considered the seventeen reference genomes of different species and subspecies under the Betacoronavirus genus to identify lectin fold/domain(s) types. We have employed three strategies for characterizing lectin fold/domain(s). The strategies include the sequence-based search against the conserved domain database (CDD) and profile HMMER and Structure-based search against Protein Data Bank (PDB) and unified platform of lectins UniLectin3D database. Interestingly, both the identified proteins, namely Hemagglutinin-esterase (HE) and Spike (S) protein, were localized on viral membranes and played a pivotal role in host-pathogen interactions. These protein structures are fabricated by most pliable β-strands forming varied architectures and topologies, such as β-sandwich, jelly-roll fold, β-barrel, β-prism, β-trefoil, β-propeller and β-hairpins. The identified lectin fold/domain(s) were compared with the characterized ones and were docked with Sia using HADDOCK, and the binding affinity was calculated using the PRODIGY server. Molecular docking studies reveal that all the identified lectin fold/domains agree with the Canyon hypothesis. Furthermore, it could be observed that coronaviruses are constantly evolving by shedding their extra baggage. The latter variants were found to have only the lectin domain but not the esterase domain.