Single-domain antibodies applied as antiviral immunotherapeutics.

Viral infections have been the cause of high mortality rates throughout different periods in history. Over the last two decades, outbreaks caused by zoonotic diseases and transmitted by arboviruses have had a significant impact on human health. The emergence of viral infections in different parts of the world encourages the search for new inputs to fight pathologies of viral origin. Antibodies represent the predominant class of new drugs developed in recent years and approved for the treatment of various human diseases, including cancer, autoimmune and infectious diseases. A promising group of antibodies are single-domain antibodies derived from camelid heavy chain immunoglobulins, or VHHs, are biomolecules with nanometric dimensions and unique pharmaceutical and biophysical properties that can be used in the diagnosis and immunotherapy of viral infections. For viral neutralization to occur, VHHs can act in different stages of the viral cycle, including the actual inhibition of infection, to hindering viral replication or assembly. This review article addresses advances involving the use of VHHs in therapeutic propositions aimed to battle different viruses that affect human health.

Engineering of single-domain antibodies for next-generation snakebite antivenoms.

Given the magnitude of the global snakebite crisis, strategies to ensure the quality of antivenom, as well as the availability and sustainability of its supply are under development by several research groups. Recombinant DNA technology has allowed the engineering of monoclonal antibodies and recombinant fragments as alternatives to conventional antivenoms. Besides having higher therapeutic efficacy, with broad neutralization capacity against local and systemic toxicity, novel antivenoms need to be safe and cost-effective. Due to the biological and physical chemical properties of camelid single-domain antibodies, with high volume of distribution to distal tissue, their modular format, and their versatility, their biotechnological application has grown considerably in recent decades. This article presents the most up-to-date developments concerning camelid single-domain-based antibodies against major toxins from snake venoms, the main venomous animals responsible for reported envenoming cases and related human deaths. A brief discussion on the composition, challenges, and perspectives of antivenoms is presented, as well as the road ahead for next-generation antivenoms based on single-domain antibodies.