Camelid VHHs as a Versatile Platform for Combating Viral Infections

Viral infections continue to pose a major global health challenge because of rapid viral evolution, immune escape, and the emergence of novel pathogens. This review examines the biological characteristics, antiviral mechanisms, production strategies, and therapeutic potential of camelid VHH as next-generation antiviral agents. The review synthesizes current evidence on the structural and functional properties of VHH, their methods of generation and engineering, and their applications against a broad range of respiratory and non-respiratory viruses. Camelid VHH nanobodies exhibit high specificity and affinity, exceptional physicochemical stability, efficient tissue penetration, and the unique ability to recognize conserved and cryptic epitopes that are often inaccessible to conventional antibodies. Engineering approaches, including multivalent, bispecific, Fc-fused, and half-life-extended constructs, further enhance their antiviral potency and pharmacokinetic properties. Evidence from preclinical studies demonstrates potent antiviral activity against multiple viral pathogens through mechanisms that include blocking viral attachment and fusion, inhibiting intracellular replication, targeting conserved viral proteins, and reducing the likelihood of viral escape. The review also highlights emerging advances in recombinant production platforms, artificial intelligence-assisted nanobody design, targeted delivery technologies, and One Health applications. Collectively, the available evidence indicates that camelid VHH represent a highly versatile and adaptable platform for antiviral therapeutics and diagnostics, with considerable potential to support pandemic preparedness and the development of broad-spectrum interventions against current and emerging viral diseases.