tetano
Editor, Senior Moderator
Open Biol
. 2024 Jun;14(6):230252.
doi: 10.1098/rsob.230252. Epub 2024 Jun 4. Structural and functional characterization of nanobodies that neutralize Omicron variants of SARS-CoV-2
Katy Cornish[SUP] 1 [/SUP], Jiandong Huo[SUP] 1 2 [/SUP], Luke Jones[SUP] 3 4 [/SUP], Parul Sharma[SUP] 5 [/SUP], Joseph W Thrush[SUP] 1 [/SUP], Sahar Abdelkarim[SUP] 1 [/SUP], Anja Kipar[SUP] 5 6 [/SUP], Siva Ramadurai[SUP] 1 [/SUP], Miriam Weckener[SUP] 1 [/SUP], Halina Mikolajek[SUP] 7 [/SUP], Sai Liu[SUP] 8 [/SUP], Imogen Buckle[SUP] 1 [/SUP], Eleanor Bentley[SUP] 5 [/SUP], Adam Kirby[SUP] 5 [/SUP], Ximeng Han[SUP] 5 [/SUP], Stephen M Laidlaw[SUP] 3 4 [/SUP], Michelle Hill[SUP] 8 [/SUP], Lauren Eyssen[SUP] 1 [/SUP], Chelsea Norman[SUP] 1 [/SUP], Audrey Le Bas[SUP] 1 [/SUP], John Clarke[SUP] 1 [/SUP], William James[SUP] 8 [/SUP], James P Stewart[SUP] 5 [/SUP], Miles Carroll[SUP] 3 4 [/SUP], James H Naismith[SUP] 1 2 [/SUP], Raymond J Owens[SUP] 1 2 [/SUP]
Affiliations
The Omicron strains of SARS-CoV-2 pose a significant challenge to the development of effective antibody-based treatments as immune evasion has compromised most available immune therapeutics. Therefore, in the 'arms race' with the virus, there is a continuing need to identify new biologics for the prevention or treatment of SARS-CoV-2 infections. Here, we report the isolation of nanobodies that bind to the Omicron BA.1 spike protein by screening nanobody phage display libraries previously generated from llamas immunized with either the Wuhan or Beta spike proteins. The structure and binding properties of three of these nanobodies (A8, H6 and B5-5) have been characterized in detail providing insight into their binding epitopes on the Omicron spike protein. Trimeric versions of H6 and B5-5 neutralized the SARS-CoV-2 variant of concern BA.5 both in vitro and in the hamster model of COVID-19 following nasal administration. Thus, either alone or in combination could serve as starting points for the development of new anti-viral immunotherapeutics.
Keywords: COVID-19; Omicrons; SARS-CoV-2; nanobodies; spike protein.
. 2024 Jun;14(6):230252.
doi: 10.1098/rsob.230252. Epub 2024 Jun 4. Structural and functional characterization of nanobodies that neutralize Omicron variants of SARS-CoV-2
Katy Cornish[SUP] 1 [/SUP], Jiandong Huo[SUP] 1 2 [/SUP], Luke Jones[SUP] 3 4 [/SUP], Parul Sharma[SUP] 5 [/SUP], Joseph W Thrush[SUP] 1 [/SUP], Sahar Abdelkarim[SUP] 1 [/SUP], Anja Kipar[SUP] 5 6 [/SUP], Siva Ramadurai[SUP] 1 [/SUP], Miriam Weckener[SUP] 1 [/SUP], Halina Mikolajek[SUP] 7 [/SUP], Sai Liu[SUP] 8 [/SUP], Imogen Buckle[SUP] 1 [/SUP], Eleanor Bentley[SUP] 5 [/SUP], Adam Kirby[SUP] 5 [/SUP], Ximeng Han[SUP] 5 [/SUP], Stephen M Laidlaw[SUP] 3 4 [/SUP], Michelle Hill[SUP] 8 [/SUP], Lauren Eyssen[SUP] 1 [/SUP], Chelsea Norman[SUP] 1 [/SUP], Audrey Le Bas[SUP] 1 [/SUP], John Clarke[SUP] 1 [/SUP], William James[SUP] 8 [/SUP], James P Stewart[SUP] 5 [/SUP], Miles Carroll[SUP] 3 4 [/SUP], James H Naismith[SUP] 1 2 [/SUP], Raymond J Owens[SUP] 1 2 [/SUP]
Affiliations
- PMID: 38835241
- DOI: 10.1098/rsob.230252
The Omicron strains of SARS-CoV-2 pose a significant challenge to the development of effective antibody-based treatments as immune evasion has compromised most available immune therapeutics. Therefore, in the 'arms race' with the virus, there is a continuing need to identify new biologics for the prevention or treatment of SARS-CoV-2 infections. Here, we report the isolation of nanobodies that bind to the Omicron BA.1 spike protein by screening nanobody phage display libraries previously generated from llamas immunized with either the Wuhan or Beta spike proteins. The structure and binding properties of three of these nanobodies (A8, H6 and B5-5) have been characterized in detail providing insight into their binding epitopes on the Omicron spike protein. Trimeric versions of H6 and B5-5 neutralized the SARS-CoV-2 variant of concern BA.5 both in vitro and in the hamster model of COVID-19 following nasal administration. Thus, either alone or in combination could serve as starting points for the development of new anti-viral immunotherapeutics.
Keywords: COVID-19; Omicrons; SARS-CoV-2; nanobodies; spike protein.