Human noroviruses pose a significant global health threat, causing acute gastroenteritis with no available vaccines or antiviral drugs. While most healthy individuals recover, the virus can be life-threatening for vulnerable populations. Annual estimates indicate 684 million illnesses and 212,000 deaths attributed to human noroviruses.
University of Michigan researchers have explored a novel approach to neutralize human noroviruses. Their study, published in Nature Communications, investigated the use of nanobodies—tiny antibodies produced by llamas. Llamas, camels, and alpacas produce antibodies similar to humans, but llama nanobodies are about one-tenth of the size of human antibodies.
The researchers, led by B V Venkataram Prasad, tested a nanobody named M4, which bound to the predominant GII.4 strain of norovirus. Surprisingly, M4 not only neutralized the current GII.4 strain but also its older variants. The researchers used human intestinal organoids, mini guts grown in the lab, to test the nanobodies' ability to prevent live viruses from infecting cells.
Crystallography and other techniques revealed that the M4 nanobody recognized a hidden pocket in norovirus particles exposed during structural changes. The virus particles alternated between a resting, compact state and a raised state, believed to be crucial for cell binding and infection. M4, acting like a wedge, bound to the exposed pocket, trapping the virus in an elevated, unstable state. This prevented the virus from returning to the compact, stable state, effectively disassembling the particles and halting the infection.
The study's significance lies in uncovering the dynamics of norovirus particles, emphasizing the importance of considering viral particle dynamics in vaccine design. The findings suggest a potential therapeutic role for llama nanobodies in combating human norovirus infections, offering a new avenue for the development of preventive and therapeutic approaches for this serious global health concern.