8C1V

SARS-CoV-2 S-trimer (3 RBDs up) bound to TriSb92, fitted into cryo-EM map

Summary for 8C1V

• Entry DOI: 10.2210/pdb8c1v/pdb
• EMDB information: 16383
• Descriptor: Spike glycoprotein, Sb92, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-2 spike, sherpabody, viral protein, coronavirus
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 6
• Total formula weight: 404600.45

Authors

Huiskonen, J.T.,Rissanen, I.,Hannula, L. (deposition date: 2022-12-21, release date: 2023-04-19)

Primary citation

Makela, A.R.,Ugurlu, H.,Hannula, L.,Kant, R.,Salminen, P.,Fagerlund, R.,Maki, S.,Haveri, A.,Strandin, T.,Kareinen, L.,Hepojoki, J.,Kuivanen, S.,Levanov, L.,Pasternack, A.,Naves, R.A.,Ritvos, O.,Osterlund, P.,Sironen, T.,Vapalahti, O.,Kipar, A.,Huiskonen, J.T.,Rissanen, I.,Saksela, K.
Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants.
Nat Commun, 14:1637-1637, 2023

PubMed 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.

PubMed: 36964125
DOI: 10.1038/s41467-023-37290-6

Experimental method

ELECTRON MICROSCOPY (2.9 Å)