Key result
MNV-neutralizing nanobodies directly inhibited essential capsid functions by blocking the receptor-binding site or interfering with structural modifications associated with cofactor binding.
Nanobodies targeting specific vulnerable regions of the norovirus capsid can inhibit essential viral functions, providing structural insights for developing human norovirus antivirals.
Nanobody mechanisms merit preclinical antiviral testing; extends capsid biology but leaves open human norovirus translation.
This research discovered and analyzed two different types of MNV-neutralizing nanobodies. The top-binding nanobodies sterically inhibited the receptor-binding site, whereas the dimeric-binding nanobodies interfered with a structural modification associated with cofactor binding. Moreover, we found that the capsid contained a number of vulnerable regions that were essential for viral replication. In fact, the capsid appeared to be organized in a state of flux, which could be important for cofactor/receptor-binding functions. Blocking these capsid-binding events with nanobodies directly inhibited essential capsid functions. Moreover, a number of MNV-specific nanobody binding epitopes were comparable to human norovirus-specific nanobody inhibitors. Therefore, this additional structural and inhibition information could be further exploited in the development of human norovirus antivirals.
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Koromyslova et al. (2020) studied Norovirus. MNV-neutralizing nanobodies was evaluated on Viral neutralization and structural inhibition. MNV-neutralizing nanobodies directly inhibited essential capsid functions by blocking the receptor-binding site or interfering with structural modifications associated with cofactor binding.
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