tetano
Editor, Senior Moderator
PLoS Pathog
. 2024 Nov 11;20(11):e1012625.
doi: 10.1371/journal.ppat.1012625. eCollection 2024 Nov. Super broad and protective nanobodies against Sarbecoviruses including SARS-CoV-1 and the divergent SARS-CoV-2 subvariant KP.3.1.1
Haodi Dong[SUP] 1 [/SUP], Runhong Zhou[SUP] 2 3 4 [/SUP], Jing Chen[SUP] 5 [/SUP], Jing Wei[SUP] 1 [/SUP], Zimeng Wei[SUP] 1 [/SUP], Ziqing Yang[SUP] 1 [/SUP], Kun Zhu[SUP] 1 [/SUP], Yufan Yang[SUP] 1 [/SUP], Qianqian Yang[SUP] 1 [/SUP], Na Liu[SUP] 2 [/SUP], Yuting Chen[SUP] 2 [/SUP], Yuhan Wu[SUP] 1 [/SUP], Yan Liang[SUP] 1 [/SUP], Yige Zeng[SUP] 1 [/SUP], Qile Guo[SUP] 1 [/SUP], Mingxi Li[SUP] 1 [/SUP], Sisi Shan[SUP] 1 [/SUP], Han Wang[SUP] 1 [/SUP], Mengyue Niu[SUP] 1 [/SUP], Isabella Yunfei Zeng[SUP] 6 [/SUP], Xuanling Shi[SUP] 1 [/SUP], Qi Zhang[SUP] 1 [/SUP], Xinquan Wang[SUP] 5 [/SUP], Zhiwei Chen[SUP] 2 3 4 [/SUP], Linqi Zhang[SUP] 1 7 8 [/SUP]
Affiliations
The ongoing evolution and immune escape of SARS-CoV-2, alongside the potential threat of SARS-CoV-1 and other sarbecoviruses, underscore the urgent need for effective strategies against their infection and transmission. This study highlights the discovery of nanobodies from immunized alpacas, which demonstrate exceptionally broad and potent neutralizing capabilities against the recently emerged and more divergent SARS-CoV-2 Omicron subvariants including JD.1.1, JN.1, KP.3, KP.3.1.1, as well as SARS-CoV-1 and coronaviruses from bats and pangolins utilizing receptor ACE2. Among these, Tnb04-1 emerges as the most broad and potent, binding to a conserved hydrophobic pocket in the spike's receptor-binding domain, distinct from the ACE2 binding site. This interaction disrupts the formation of a proteinase K-resistant core, crucial for viral-cell fusion. Notably, intranasal administration of Tnb04-1 in Syrian hamsters effectively prevented respiratory infection and transmission of the authentic Omicron XBB.1.5 subvariant. Thus, Thb04-1 holds promise in combating respiratory acquisition and transmission of diverse sarbecoviruses.
. 2024 Nov 11;20(11):e1012625.
doi: 10.1371/journal.ppat.1012625. eCollection 2024 Nov. Super broad and protective nanobodies against Sarbecoviruses including SARS-CoV-1 and the divergent SARS-CoV-2 subvariant KP.3.1.1
Haodi Dong[SUP] 1 [/SUP], Runhong Zhou[SUP] 2 3 4 [/SUP], Jing Chen[SUP] 5 [/SUP], Jing Wei[SUP] 1 [/SUP], Zimeng Wei[SUP] 1 [/SUP], Ziqing Yang[SUP] 1 [/SUP], Kun Zhu[SUP] 1 [/SUP], Yufan Yang[SUP] 1 [/SUP], Qianqian Yang[SUP] 1 [/SUP], Na Liu[SUP] 2 [/SUP], Yuting Chen[SUP] 2 [/SUP], Yuhan Wu[SUP] 1 [/SUP], Yan Liang[SUP] 1 [/SUP], Yige Zeng[SUP] 1 [/SUP], Qile Guo[SUP] 1 [/SUP], Mingxi Li[SUP] 1 [/SUP], Sisi Shan[SUP] 1 [/SUP], Han Wang[SUP] 1 [/SUP], Mengyue Niu[SUP] 1 [/SUP], Isabella Yunfei Zeng[SUP] 6 [/SUP], Xuanling Shi[SUP] 1 [/SUP], Qi Zhang[SUP] 1 [/SUP], Xinquan Wang[SUP] 5 [/SUP], Zhiwei Chen[SUP] 2 3 4 [/SUP], Linqi Zhang[SUP] 1 7 8 [/SUP]
Affiliations
- PMID: 39527594
- PMCID: PMC11554226
- DOI: 10.1371/journal.ppat.1012625
The ongoing evolution and immune escape of SARS-CoV-2, alongside the potential threat of SARS-CoV-1 and other sarbecoviruses, underscore the urgent need for effective strategies against their infection and transmission. This study highlights the discovery of nanobodies from immunized alpacas, which demonstrate exceptionally broad and potent neutralizing capabilities against the recently emerged and more divergent SARS-CoV-2 Omicron subvariants including JD.1.1, JN.1, KP.3, KP.3.1.1, as well as SARS-CoV-1 and coronaviruses from bats and pangolins utilizing receptor ACE2. Among these, Tnb04-1 emerges as the most broad and potent, binding to a conserved hydrophobic pocket in the spike's receptor-binding domain, distinct from the ACE2 binding site. This interaction disrupts the formation of a proteinase K-resistant core, crucial for viral-cell fusion. Notably, intranasal administration of Tnb04-1 in Syrian hamsters effectively prevented respiratory infection and transmission of the authentic Omicron XBB.1.5 subvariant. Thus, Thb04-1 holds promise in combating respiratory acquisition and transmission of diverse sarbecoviruses.