Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants

Anna R. Mäkelä, Hasan Uğurlu, Liina Hannula, Ravi Kant, Petja Salminen, Riku Fagerlund, Sanna Mäki, Anu Haveri, Tomas Strandin, Lauri Kareinen, Jussi Hepojoki, Suvi Kuivanen, Lev Levanov, Arja Pasternack, Rauno A. Naves, Olli Ritvos, Pamela Österlund, Tarja Sironen, Olli Vapalahti, Anja Kipar, Juha T. Huiskonen, Ilona Rissanen and Kalle Saksela ()
Additional contact information
Anna R. Mäkelä: University of Helsinki
Hasan Uğurlu: University of Helsinki
Liina Hannula: University of Helsinki
Ravi Kant: University of Helsinki
Petja Salminen: University of Helsinki
Riku Fagerlund: University of Helsinki
Sanna Mäki: University of Helsinki
Anu Haveri: Finnish Institute for Health and Welfare
Tomas Strandin: University of Helsinki
Lauri Kareinen: University of Helsinki
Jussi Hepojoki: University of Helsinki
Suvi Kuivanen: University of Helsinki
Lev Levanov: University of Helsinki
Arja Pasternack: University of Helsinki
Rauno A. Naves: University of Helsinki
Olli Ritvos: University of Helsinki
Pamela Österlund: Finnish Institute for Health and Welfare
Tarja Sironen: University of Helsinki
Olli Vapalahti: University of Helsinki
Anja Kipar: University of Helsinki
Juha T. Huiskonen: University of Helsinki
Ilona Rissanen: University of Helsinki
Kalle Saksela: University of Helsinki

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37290-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37290-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37290-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().