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

Mäkelä, AR; Uğurlu, H; Hannula, L; Kant, R; Salminen, P; Fagerlund, R; Mäki, S; Haveri, A; Strandin, T; Kareinen, L; Hepojoki, J; Kuivanen, S; Levanov, L; Pasternack, A; Naves, RA; Ritvos, O; Österlund, P; Sironen, T; Vapalahti, O; Kipar, A; Huiskonen, JT; Rissanen, I; Saksela, K

COVID-19 Collection

Journal article

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

Abstract:: Here the authors describe a small antibody-like protein that can prevent infection by diverse SARS-CoV-2 variants in cell culture and in mice that were intranasally treated with this inhibitor before or shortly after being exposed to the virus.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.Peer reviewe

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Mäkelä, A. R., Uğurlu, H., Hannula, L., Kant, R., Salminen, P., Fagerlund, R., Mäki, S., Haveri, A., Strandin, T., Kareinen, L., Hepojoki, J., Kuivanen, S., Levanov, L., Pasternack, A., Naves, R. A., Ritvos, O., Österlund, P., Sironen, T., Vapalahti, O., … Saksela, K. (2023). Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants. Nature Communications, 14(1), 1637–1637.

MLA Style

Mäkelä, AR, et al. “Intranasal Trimeric Sherpabody Inhibits SARS-CoV-2 Including Recent Immunoevasive Omicron Subvariants.” Nature Communications, vol. 14, no. 1, 2023, pp. 1637–37.

Chicago Style

Mäkelä, AR, H Uğurlu, L Hannula, et al. 2023. “Intranasal Trimeric Sherpabody Inhibits SARS-CoV-2 Including Recent Immunoevasive Omicron Subvariants.” Nature Communications 14 (1): 1637–37.
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