9RIU
Co-crystal of broadly neutralizing VHH in complex with short neurotoxin 1 (P01426) Naja pallida
Summary for 9RIU
| Entry DOI | 10.2210/pdb9riu/pdb |
| Descriptor | Variable Domain of Heavy-Chain only Antibody (VHH), Short neurotoxin 1, NICKEL (II) ION, ... (4 entities in total) |
| Functional Keywords | nanobody, vhh, antibody, toxin, snake toxin, snake venom, neutralizing |
| Biological source | Vicugna pacos More |
| Total number of polymer chains | 4 |
| Total formula weight | 42351.00 |
| Authors | Burlet, N.J.,Laustsen, A.H.,Morth, J.P. (deposition date: 2025-06-11, release date: 2025-11-05, Last modification date: 2025-11-12) |
| Primary citation | Ahmadi, S.,Burlet, N.J.,Benard-Valle, M.,Guadarrama-Martinez, A.,Kerwin, S.,Cardoso, I.A.,Marriott, A.E.,Edge, R.J.,Crittenden, E.,Neri-Castro, E.,Fernandez-Quintero, M.L.,Nguyen, G.T.T.,O'Brien, C.,Wouters, Y.,Kalogeropoulos, K.,Thumtecho, S.,Ebersole, T.W.,Dahl, C.H.,Glegg-Sorensen, E.U.,Jansen, T.,Boddum, K.,Manousaki, E.,Rivera-de-Torre, E.,Ward, A.B.,Morth, J.P.,Alagon, A.,Mackessy, S.P.,Ainsworth, S.,Menzies, S.K.,Casewell, N.R.,Jenkins, T.P.,Ljungars, A.,Laustsen, A.H. Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites. Nature, 2025 Cited by PubMed Abstract: Each year, snakebite envenoming claims thousands of lives and causes severe injury to victims across sub-Saharan Africa, many of whom depend on antivenoms derived from animal plasma as their sole treatment option. Traditional antivenoms are expensive, can cause adverse immunological reactions, offer limited efficacy against local tissue damage and are often ineffective against all medically relevant snake species. There is thus an urgent unmet medical need for innovation in snakebite envenoming therapy. However, developing broad-spectrum treatments is highly challenging owing to the vast diversity of venomous snakes and the complex and variable composition of their venoms. Here we addressed this challenge by immunizing an alpaca and a llama with the venoms of 18 different snakes, including mambas, cobras and a rinkhals, constructing phage display libraries, and identifying high-affinity broadly neutralizing nanobodies. We combined eight of these nanobodies into a defined oligoclonal mixture, resulting in an experimental polyvalent recombinant antivenom that was capable of neutralizing seven toxin families or subfamilies. This antivenom effectively prevented venom-induced lethality in vivo across 17 African elapid snake species and markedly reduced venom-induced dermonecrosis for all tested cytotoxic venoms. The recombinant antivenom performed better than a currently used plasma-derived antivenom and therefore shows considerable promise for comprehensive, continent-wide protection against snakebites by all medically relevant African elapids. PubMed: 41162699DOI: 10.1038/s41586-025-09661-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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