8C1V

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

8C1V の概要

• エントリーDOI: 10.2210/pdb8c1v/pdb
• EMDBエントリー: 16383
• 分子名称: Spike glycoprotein, Sb92, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: sars-cov-2 spike, sherpabody, viral protein, coronavirus
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 404600.45

構造登録者

Huiskonen, J.T.,Rissanen, I.,Hannula, L. (登録日: 2022-12-21, 公開日: 2023-04-19, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.9 Å)