A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo

Cell Rep Med. 2022 Oct 18;3(10):100774. doi: 10.1016/j.xcrm.2022.100774. Epub 2022 Sep 29.


"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV and SARS-CoV-2 infection in vivo. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Mechanistic assays show that H84T-BanLec targets virus entry. High-speed atomic force microscopy depicts real-time multimolecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modeling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the drug compound's broad-spectrum antiviral activity and the lack of resistant mutants.

Keywords: MERS-CoV; SARS-CoV-2; antiviral; atomic force microscopy; banana; coronavirus; lectin; single-molecule force spectroscopy; spike; treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents / pharmacology
  • COVID-19*
  • Humans
  • Lectins / pharmacology
  • Mannose / pharmacology
  • Middle East Respiratory Syndrome Coronavirus*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / pharmacology


  • Lectins
  • Mannose
  • Angiotensin-Converting Enzyme 2
  • Spike Glycoprotein, Coronavirus
  • Antiviral Agents
  • spike protein, SARS-CoV-2