The Disorderly Nature of Caliciviruses.

An intrinsically disordered protein (IDP) or region (IDR) lacks or has little protein structure but still maintains function. This lack of structure creates flexibility and fluidity, allowing multiple protein conformations and potentially transient interactions with more than one partner. Caliciviruses are positive-sense ssRNA viruses, containing a relatively small genome of 7.

Crystal Structure of Inhibitor-Bound GII.4 Sydney 2012 Norovirus 3C-Like Protease.

Norovirus is the leading cause of viral gastroenteritis worldwide, and there are no approved vaccines or therapeutic treatments for chronic or severe norovirus infections. The structural characterisation of the norovirus protease and drug development has predominantly focused upon GI.1 noroviruses, despite most global outbreaks being caused by GII.

P Glutamine isosteres in the design of inhibitors of 3C/3CL protease of human viruses of the class.

Viral infections are one of the leading causes of acute morbidity in humans and much endeavour has been made by the synthetic community for the development of drugs to treat associated diseases. Peptide-based enzyme inhibitors, usually short sequences of three or four residues, are one of the classes of compounds currently under development for enhancement of their activity and pharmaceutical properties. This review reports the advances made in the design of inhibitors targeting the family of highly conserved viral proteases 3C/3CL, which play a key role in viral replication and present minimal homology with mammalian proteases.

Murine Norovirus: Additional Protocols for Basic and Antiviral Studies.

Murine norovirus (MNV) is a positive-sense, plus-stranded RNA virus in the Caliciviridae family. Viruses in this family replicate in the intestine and are transmitted by the fecal-oral route. MNV is related to the human noroviruses, which cause the majority of nonbacterial gastroenteritis worldwide.

An Isomer of Galidesivir That Potently Inhibits Influenza Viruses and Members of the Order.

We report for the first time the antiviral activities of two (antiviral imino--nucleosides) and , structurally related to galidesivir (Immucillin A, BCX4430). An containing the 4-aminopyrrolo[2,1-][1,2,4-triazine] nucleobase found in remdesivir exhibited submicromolar inhibition of multiple strains of influenza A and B viruses, as well as members of the order. We also report the first syntheses of ProTide prodrugs of monophosphates, which unexpectedly displayed poorer viral inhibition than their parent nucleosides .

Protein Nucleotidylylation in +ssRNA Viruses.

Nucleotidylylation is a post-transcriptional modification important for replication in the picornavirus supergroup of RNA viruses, including members of the , , and virus families. This modification occurs when the RNA-dependent RNA polymerase (RdRp) attaches one or more nucleotides to a target protein through a nucleotidyl-transferase reaction. The most characterized nucleotidylylation target is VPg (viral protein genome-linked), a protein linked to the 5' end of the genome in , and .

Norovirus VPg Binds RNA through a Conserved N-Terminal K/R Basic Patch.

The viral protein genome-linked (VPg) of noroviruses is a multi-functional protein that participates in essential roles during the viral replication cycle. Predictive analyses indicate that murine norovirus (MNV) VPg contains a disordered N-terminal region with RNA binding potential. VPg proteins were expressed with an N-terminal spidroin fusion protein in insect cells and the interaction with RNA investigated by electrophoretic mobility shift assays (EMSA) against a series of RNA probes (pentaprobes) representing all possible five nucleotide combinations.

Cell Cycle Arrest is a Conserved Function of Norovirus VPg Proteins.

Murine norovirus (MNV) viral protein genome-linked (VPg) manipulates the cell cycle to induce a G0/G1 arrest and gain a beneficial replication environment. All viruses of the norovirus genus encode a VPg protein; however, it is unknown if the G0/G1 arrest induced by MNV VPg is conserved in other members of the genus. RNA transcripts encoding a representative viral VPg from five norovirus genogroups were transfected into RAW-Blue murine macrophages, and the percentage of cells in each phase of the cell cycle was determined.

Multiplex-PCR for the detection of viruses in the CSF of infants and young children.

We aimed to establish the utility of the Fast-track diagnostics Viral meningitis multiplex PCR kit for the diagnosis of central nervous system infection in infants. The multiplex assay had reduced sensitivity for the detection of enterovirus, the predominant pathogen in young infants, when compared to our in-house singleplex PCR. In our infant population, multiple singleplex PCR assays perform better than a multiplex assay for the detection of CSF viruses.