The pharmacokinetics, bio-distribution and therapeutic efficacy of a trimeric nanobody against SARS-CoV-2 in the Syrian golden hamster COVID-19 model

The rapid emergence of SARS-CoV-2 prompted the development of anti-viral therapies and vaccines to combat the COVID-19 pandemic. The continuous emergence of variants of concern has necessitated the development of platforms that can be rapidly adapted. Nanobodies, offer advantages over conventional monoclonal antibodies, including low molecular weight, high antigen-binding affinity, enhanced tissue penetration, blood-brain barrier permeability, and simplified production. Previous studies have demonstrated the efficacy of nanobodies against respiratory viruses such as SARS-CoV-2, respiratory syncytial virus, and influenza A virus in animal models. We previously reported the protective effects of nanobody trimers against SARS-CoV-2. However, pharmacokinetic and biodistribution data for nanobodies remain limited. To address this, we evaluated the efficacy, biodistribution and longevity of action of a nanobody trimer (A8) administered intranasally (IN) or intraperitoneally (IP) in Syrian golden hamsters. Our findings revealed that the A8 trimer reached peak concentrations shortly after administration and was subsequently cleared from the system via both routes. Importantly, early administration of A8 trimer reduced virus mediated weight loss and viral load compared with untreated controls supporting its potential as a therapeutic candidate for SARS-CoV-2 infection.