Bridging Viral Glycobiology and Lectin Biotechnology for Antiviral and Diagnostic Strategies

Lectins, proteins that reversibly bind specific glycan motifs, offer dual utility as molecular probes or inhibitors of virus-host interactions. This review explores the molecular interactions between lectins and viral envelope glycoproteins, emphasizing their applications as antiviral agents and diagnostic tools. Enveloped viruses, such as HIV, Influenza, Herpesviruses, and Coronaviruses, exhibit dense glycosylation on their surface proteins, forming a glycan shield rich in high-mannose and complex glycans crucial for viral processes and immune evasion. Lectins exploit these glycan shields by selectively targeting conserved glycosylation sites on key viral proteins like gp120 (HIV), hemagglutinin (Influenza), spike (SARS-CoV-2), and glycoprotein D (HSV), thereby interfering with viral entry. Potent inhibitory activity across diverse virus families has been demonstrated for natural lectins such as griffithsin (GRFT), cyanovirin (CV-N), and banana lectin (BanLec), with novel fungal and algal lectins continually expanding the list. Concurrently, lectin-based biosensors utilizing electrochemical, plasmonic, and microfluidic platforms, often enhanced by nanomaterials or aptamers, enable sensitive and specific detection of glycosylated viral targets. Despite challenges including potential immunogenicity and production scalability, ongoing bioengineering efforts aim to refine lectin specificity, reduce toxicity, and enhance overall functionality. These collective advances showcase the role of lectins as versatile molecular tools for the detection, inhibition, and mechanistic study of viral pathogens.