The role of venom proteomics and single-domain antibodies for antivenoms: Progress in snake envenoming treatment

Single-domain antibodies (sdAbs) hold promise for developing new biopharmaceuticals to treat neglected tropical diseases (NTDs), including snakebites, which are severe and occur frequently. In addition, limitations of conventional snakebite treatments, especially in terms of local action, and the global antivenom crisis incentivize the use of this biotechnological tool to design next-generation snakebite antivenoms. Conventional antivenoms for snakebite treatment are usually composed of immunoglobulin G or F(ab′)2 fragments derived from the plasma of immunized animals. sdAbs, the smallest antigen-binding fragments, are derived from the variable domains of camelid heavy-chain antibodies. sdAbs may have some advantages over conventional antivenoms for local toxicity, such as better penetration into tissues due to their small size, and high solubility and affinity for venom antigens due to their unique antigen-binding loops and ability to access cryptic epitopes. We present an overview of current antivenom therapy in the context of sdAb development for toxin neutralization. Furthermore, strategies are presented for identifying snake venom's major toxins as well as for developing antisnake toxin sdAbs by employing proteomic tools for toxin neutralization.