biostudies-literatureUnknown6(1)Li FNeutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with liveCommunications biology592https://www.ebi.ac.uk/biostudies/studies/S-EPMC10234585biostudies-literatureA spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.PMC10234585Han PXie YLi FZhang HJiang SWang HLi MYang XLu LSu SDai QQi XZhang XFan LLiang JLin HWang WWang XXu WXu YfalseA spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live2023-01-01T00:00:00Z2023 Jun2026-07-14T20:07:57.292Z2025-02-19T04:46:07.981ZS-EPMC102345853726408610.1038/s42003-023-04955-3