8PK3

CryoEM reconstruction of hemagglutinin HK68 of Influenza A virus bound to an Affimer reagent

Summary for 8PK3

• Entry DOI: 10.2210/pdb8pk3/pdb
• EMDB information: 17724
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, Affimer molecule (A31), ... (6 entities in total)
• Functional Keywords: complex, inhibitor, cryoem, antiviral, antiviral protein
• Biological source: Influenza A virus; More
• Total number of polymer chains: 9
• Total formula weight: 203494.69

Authors

Debski-Antoniak, O.,Flynn, A.,Klebl, D.P.,Tiede, C.,Muench, S.,Tomlinson, D.,Fontana, J. (deposition date: 2023-06-24, release date: 2024-01-03, Last modification date: 2025-07-02)

Primary citation

Debski-Antoniak, O.,Flynn, A.,Klebl, D.P.,Rojas Rechy, M.H.,Tiede, C.,Wilson, I.A.,Muench, S.P.,Tomlinson, D.,Fontana, J.
Exploiting the Affimer platform against influenza A virus.
Mbio, 15:e0180424-e0180424, 2024

PubMed Abstract: Influenza A virus (IAV) is well known for its pandemic potential. While current surveillance and vaccination strategies are highly effective, therapeutic approaches are often short-lived due to the high mutation rates of IAV. Recently, monoclonal antibodies (mAbs) have emerged as a promising therapeutic approach, both against current strains and future IAV pandemics. In addition to mAbs, several antibody-like alternatives exist, which aim to improve upon mAbs. Among these, Affimers stand out for their short development time, high expression levels in , and animal-free production. In this study, we utilized the Affimer platform to isolate and produce specific and potent inhibitors of IAV. Using a monomeric version of the IAV trimeric hemagglutinin (HA) fusion protein, we isolated 12 Affimers that inhibit IAV infection . Two of these Affimers were characterized in detail and exhibited nanomolar-binding affinities to the target H3 HA protein, specifically binding to the HA1 head domain. Cryo-electron microscopy (cryo-EM), employing a novel spray approach to prepare cryo-grids, allowed us to image HA-Affimer complexes. Combined with functional assays, we determined that these Affimers inhibit IAV by blocking the interaction of HA with the host-cell receptor, sialic acid. Furthermore, these Affimers inhibited IAV strains closely related to the one used for their isolation. Overall, our results support the use of Affimers as a viable alternative to existing targeted therapies for IAV and highlight their potential as diagnostic reagents.

PubMed: 39037231
DOI: 10.1128/mbio.01804-24

Experimental method

ELECTRON MICROSCOPY (3.4 Å)