9MVU

C6 Herpes Virus Simplex Neutralizing Nanobody Bound to HSV Glycoprotein gB

9MVU の概要

• エントリーDOI: 10.2210/pdb9mvu/pdb
• EMDBエントリー: 48671
• 分子名称: Envelope glycoprotein B, C6 Neutralizing Nanobody (3 entities in total)
• 機能のキーワード: neutralizing antibody, antiviral protein
• 由来する生物種: Human herpesvirus 1 (strain 17) (HHV-1, Human herpes simplex virus 1); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 289133.56

構造登録者

Viadiu, H.,Abernathy, E.,Lee, C.V.,Hung, M.,Yu, Y.,Xing, W.,Yu, X. (登録日: 2025-01-16, 公開日: 2025-08-13)

主引用文献

Lee, C.V.,Viadiu, H.,Kalamkar, A.,Bernstein, D.I.,Pae, A.,Yu, X.,Wong, S.,Bravo, F.J.,Ding, S.,Seto, E.,Hung, M.,Yu, Y.,Xing, W.,Papalia, G.A.,Kan, W.,Carr, B.,Thomas, M.,Tong, L.,Desai, P.,Jarrousse, N.,Mercier, A.,Holdorf, M.M.,Fletcher, S.P.,Abernathy, E.
Identification and engineering of potent bispecific antibodies that protect against herpes simplex virus recurrent disease.
Cell Rep, 44:116063-116063, 2025

PubMed Abstract: Herpes simplex virus (HSV) causes lifelong infections, including oral and genital herpes. There is no vaccine, and current antivirals are only partially effective at reducing symptoms and transmission. Therapeutic antibodies offer a potentially long-acting treatment option, although efforts to pursue this have been limited. We performed an alpaca immunization campaign and discovered high-affinity antibodies that both neutralized and completely blocked cell-to-cell spread (CCS), a key mechanism by which HSV evades neutralizing antibodies. Unexpectedly, we found that engineering antibodies into a bispecific format targeting two viral glycoproteins dramatically increased antiviral potency. Solving the structures of three antibodies using cryo-electron microscopy (cryo-EM) revealed a mechanistic understanding of how the bispecific format could enhance potency. Lastly, these bispecific antibodies significantly reduced lesion development in the guinea pig model of genital herpes, demonstrating that delayed dosing after latency establishment can reduce disease and confirming their potential as a transformative treatment option.

PubMed: 40716063
DOI: 10.1016/j.celrep.2025.116063

実験手法

ELECTRON MICROSCOPY (2.2 Å)