tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2021 Jul 19;1-31.
doi: 10.1080/22221751.2021.1957720. Online ahead of print.
Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants
Wenbo Wang[SUP] 1 [/SUP], Qianqian Li[SUP] 2 3 [/SUP], Jiajing Wu[SUP] 2 4 [/SUP], Yu Hu[SUP] 5 6 [/SUP], Gang Wu[SUP] 1 [/SUP], Chuanfei Yu[SUP] 1 [/SUP], Kangwei Xu[SUP] 7 [/SUP], Xumei Liu[SUP] 1 8 [/SUP], Qihui Wang[SUP] 5 [/SUP], Weijin Huang[SUP] 2 [/SUP], Lan Wang[SUP] 1 [/SUP], Youchun Wang[SUP] 2 [/SUP]
Affiliations
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 development of anti-SARS-CoV-2 strategies against variants. Here, we collected twelve 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 hemagglutination 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.
Keywords: N-linked glycosylation; SARS-CoV-2; antiviral lectin; carbohydrate binding protein; pseudovirus.
. 2021 Jul 19;1-31.
doi: 10.1080/22221751.2021.1957720. Online ahead of print.
Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants
Wenbo Wang[SUP] 1 [/SUP], Qianqian Li[SUP] 2 3 [/SUP], Jiajing Wu[SUP] 2 4 [/SUP], Yu Hu[SUP] 5 6 [/SUP], Gang Wu[SUP] 1 [/SUP], Chuanfei Yu[SUP] 1 [/SUP], Kangwei Xu[SUP] 7 [/SUP], Xumei Liu[SUP] 1 8 [/SUP], Qihui Wang[SUP] 5 [/SUP], Weijin Huang[SUP] 2 [/SUP], Lan Wang[SUP] 1 [/SUP], Youchun Wang[SUP] 2 [/SUP]
Affiliations
- PMID: 34278967
- DOI: 10.1080/22221751.2021.1957720
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 development of anti-SARS-CoV-2 strategies against variants. Here, we collected twelve 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 hemagglutination 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.
Keywords: N-linked glycosylation; SARS-CoV-2; antiviral lectin; carbohydrate binding protein; pseudovirus.