ABSTRACT The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants. Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay. The Lens culinaris -derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1. Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV. We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection. Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity. Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment. This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
【저자키워드】 SARS-CoV-2, pseudovirus, antiviral lectin, carbohydrate-binding protein, N-linked glycosylation, 【초록키워드】 ACE2, coronavirus, S protein, B.1.351, neutralization, variant, Infection, cytotoxicity, antiviral activity, anti-SARS-CoV-2, MERS-CoV, variants, Protein, specificity, Epidemic, Neutralization assay, B.1.1.7, P.1, mutants, mutant, experiment, information, glycan, binding, Amino acid, Evidence, Anti-SARS-CoV-2 Activity, mutant strain, weight loss, acute respiratory syndrome, injection, carbohydrate, GlcNAc, the epidemic, S trimer, glycosylation site, collected, conserved, inhibit, evaluated, raised, provide, against SARS-CoV, mutated, glycosylated, inhibit SARS-CoV-2, Len, Lentil, 【제목키워드】 SARS-CoV-2 variant, antiviral activity, Len, Lentil,