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-Structure paper
| タイトル | Structural and mechanistic insights into herpesvirus helicase-primase and its therapeutic inhibitors. |
|---|---|
| ジャーナル・号・ページ | Nat Microbiol, Vol. 10, Issue 12, Page 3191-3201, Year 2025 |
| 掲載日 | 2025年11月4日 |
著者 | Qing Yao / Alexandre Mercier / Arabinda Nayak / Lindsey May / Pui Yan Ho / Ariel Lewis-Ballester / Varsha Nair / Annapurna Sapre / Thomas Aeschbacher / Jit Mukherjee / Christopher Richards / Roberto Mateo / Aesop Cho / Eric Lansdon / Xinchao Yu / ![]() |
| PubMed 要旨 | The herpes simplex virus (HSV) helicase-primase (HP) complex is a promising anti-herpes therapeutic target. However, progress in developing highly effective small-molecule HP inhibitors (HPIs) for ...The herpes simplex virus (HSV) helicase-primase (HP) complex is a promising anti-herpes therapeutic target. However, progress in developing highly effective small-molecule HP inhibitors (HPIs) for the treatment of genital herpes has been hindered by the lack of structural information on the HP complex and the incomplete understanding of the mechanism of action of HPIs. Here we present the cryogenic electron microscopy structure of the HSV-1 HP apo-complex (3.8 Å), along with structures bound to pritelivir (3.2 Å) and amenamevir (3.2 Å)-two clinically active, chemically distinct HPIs. The potency of both inhibitors against HSV variants bearing mutations within the HPI binding pocket supports the high-resolution mapping of key molecular interactions while revealing residues that govern their antiviral spectrum against alphaherpesviruses. Our results provide important insight into the unique architecture of the HP complex and the mechanism of inhibition of HPIs, paving the way for the development of next-generation antivirals to treat herpesvirus infections. |
リンク | Nat Microbiol / PubMed:41188384 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.8 - 3.8 Å |
| 構造データ | EMDB-49269, PDB-9nda: EMDB-49276, PDB-9ndq: EMDB-49277, PDB-9ndt: EMDB-49290, PDB-9ndz: EMDB-49291, PDB-9ne0: EMDB-49304, PDB-9neb: EMDB-49306, PDB-9nee: EMDB-49326, PDB-9nel: |
| 化合物 | ![]() PDB-1bxb: ![]() PDB-1bxd: |
| 由来 |
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キーワード | REPLICATION / TRANSFERASE / Inhibitor / Helicase / Primase / Herpesvirus / Forked DNA / Pritelivir / TRANSFERASE/INHIBITOR / TRANSFERASE-INHIBITOR complex |
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herpesviridae (ウイルス)
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