tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Sep 29;100774.
doi: 10.1016/j.xcrm.2022.100774. Online ahead of print.
A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo
Jasper Fuk-Woo Chan[SUP] 1 [/SUP], Yoo Jin Oh[SUP] 2 [/SUP], Shuofeng Yuan[SUP] 3 [/SUP], Hin Chu[SUP] 3 [/SUP], Man-Lung Yeung[SUP] 4 [/SUP], Daniel Canena[SUP] 2 [/SUP], Chris Chung-Sing Chan[SUP] 5 [/SUP], Vincent Kwok-Man Poon[SUP] 5 [/SUP], Chris Chun-Yiu Chan[SUP] 6 [/SUP], Anna Jinxia Zhang[SUP] 7 [/SUP], Jian-Piao Cai[SUP] 6 [/SUP], Zi-Wei Ye[SUP] 6 [/SUP], Lei Wen[SUP] 6 [/SUP], Terrence Tsz-Tai Yuen[SUP] 6 [/SUP], Kenn Ka-Heng Chik[SUP] 5 [/SUP], Huiping Shuai[SUP] 5 [/SUP], Yixin Wang[SUP] 6 [/SUP], Yuxin Hou[SUP] 6 [/SUP], Cuiting Luo[SUP] 6 [/SUP], Wan-Mui Chan[SUP] 6 [/SUP], Zhenzhi Qin[SUP] 6 [/SUP], Ko-Yung Sit[SUP] 8 [/SUP], Wing-Kuk Au[SUP] 8 [/SUP], Maureen Legendre[SUP] 9 [/SUP], Rong Zhu[SUP] 2 [/SUP], Lisa Hain[SUP] 2 [/SUP], Hannah Seferovic[SUP] 2 [/SUP], Robert Tampé[SUP] 10 [/SUP], Kelvin Kai-Wang To[SUP] 11 [/SUP], Kwok-Hung Chan[SUP] 3 [/SUP], Dafydd Gareth Thomas[SUP] 12 [/SUP], Miriam Klausberger[SUP] 13 [/SUP], Cheng Xu[SUP] 14 [/SUP], James J Moon[SUP] 14 [/SUP], Johannes Stadlmann[SUP] 15 [/SUP], Josef M Penninger[SUP] 16 [/SUP], Chris Oostenbrink[SUP] 17 [/SUP], Peter Hinterdorfer[SUP] 18 [/SUP], Kwok-Yung Yuen[SUP] 19 [/SUP], David M Markovitz[SUP] 20 [/SUP]
Affiliations
Abstract
"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.
. 2022 Sep 29;100774.
doi: 10.1016/j.xcrm.2022.100774. Online ahead of print.
A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo
Jasper Fuk-Woo Chan[SUP] 1 [/SUP], Yoo Jin Oh[SUP] 2 [/SUP], Shuofeng Yuan[SUP] 3 [/SUP], Hin Chu[SUP] 3 [/SUP], Man-Lung Yeung[SUP] 4 [/SUP], Daniel Canena[SUP] 2 [/SUP], Chris Chung-Sing Chan[SUP] 5 [/SUP], Vincent Kwok-Man Poon[SUP] 5 [/SUP], Chris Chun-Yiu Chan[SUP] 6 [/SUP], Anna Jinxia Zhang[SUP] 7 [/SUP], Jian-Piao Cai[SUP] 6 [/SUP], Zi-Wei Ye[SUP] 6 [/SUP], Lei Wen[SUP] 6 [/SUP], Terrence Tsz-Tai Yuen[SUP] 6 [/SUP], Kenn Ka-Heng Chik[SUP] 5 [/SUP], Huiping Shuai[SUP] 5 [/SUP], Yixin Wang[SUP] 6 [/SUP], Yuxin Hou[SUP] 6 [/SUP], Cuiting Luo[SUP] 6 [/SUP], Wan-Mui Chan[SUP] 6 [/SUP], Zhenzhi Qin[SUP] 6 [/SUP], Ko-Yung Sit[SUP] 8 [/SUP], Wing-Kuk Au[SUP] 8 [/SUP], Maureen Legendre[SUP] 9 [/SUP], Rong Zhu[SUP] 2 [/SUP], Lisa Hain[SUP] 2 [/SUP], Hannah Seferovic[SUP] 2 [/SUP], Robert Tampé[SUP] 10 [/SUP], Kelvin Kai-Wang To[SUP] 11 [/SUP], Kwok-Hung Chan[SUP] 3 [/SUP], Dafydd Gareth Thomas[SUP] 12 [/SUP], Miriam Klausberger[SUP] 13 [/SUP], Cheng Xu[SUP] 14 [/SUP], James J Moon[SUP] 14 [/SUP], Johannes Stadlmann[SUP] 15 [/SUP], Josef M Penninger[SUP] 16 [/SUP], Chris Oostenbrink[SUP] 17 [/SUP], Peter Hinterdorfer[SUP] 18 [/SUP], Kwok-Yung Yuen[SUP] 19 [/SUP], David M Markovitz[SUP] 20 [/SUP]
Affiliations
- PMID: 36195094
- PMCID: PMC9519379
- DOI: 10.1016/j.xcrm.2022.100774
Abstract
"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.