Histo-blood group antigens (HBGAs) are important binding factors for norovirus infections. We show that two human milk oligosaccharides, 2'-fucosyllactose (2'FL) and 3-fucosyllactose (3FL), could block from to surrogate HBGA samples. found 2'FL 3FL bound at the equivalent pockets on capsid using X-ray crystallography. Our data revealed structurally mimic HBGAs. These results suggest might act as naturally occurring decoys in humans.

A recently developed human norovirus cell culture system revealed that the presence of bile enhanced or was an essential requirement for growth certain genotypes. Before this discovery, histo-blood group antigens (HBGAs) were only well-studied cofactor known noroviruses, and there evidence several genotypes poorly bound HBGAs. Therefore, purpose study to investigate how capsids interact with acids. We found acids had low-micromolar affinities GII.1, GII.10, GII.19 but did not bind GI.1,...

Human noroviruses are icosahedral single-stranded RNA viruses. The capsid protein is divided into shell (S) and protruding (P) domains, which connected by a flexible hinge region. There numerous genetically antigenically distinct noroviruses, the dominant strains evolve every other year. Vaccine antiviral development hampered difficulties in growing human norovirus cell culture continually evolving strains. Here, we show X-ray crystal structures of P domains complex with two different...

Temporal changes in the GII.4 human norovirus capsid sequences occasionally result emergence of genetic variants capable causing new epidemics. The persistence is believed to be associated with recognition numerous histo-blood group antigen (HBGA) types and antigenic drift. We found that one earliest known isolates (in 1974) a more recent epidemic variant 2012) had varied norovirus-specific monoclonal antibody (MAb) reactivities but similar HBGA binding profiles. To better understand...

Norovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation cell culture, these viruses are still challenging to grow routinely. Moreover, little known on how infects host cells, except that histo-blood group antigens (HBGAs) important binding factors for infection and entry. Antibodies bind at HBGA pocket block attachment HBGAs believed neutralize virus. However, additional neutralization epitopes elsewhere capsid likely exist impeding...

We previously identified a Nanobody (termed Nano-85) that bound to highly conserved region on the norovirus capsid. In this study, was biotinylated and gold conjugated for lateral flow immunoassay Nano-IC). showed Nano-IC assay capable of detecting at least four antigenically distinct GII genotypes, including newly emerging GII.17. clinical setting, had sensitivities equivalent other commercially available systems. The method producing results in ~5 min, which makes useful settings require...

ABSTRACT Human noroviruses are the leading cause of acute gastroenteritis in humans. Noroviruses also infect animals, such as cows, mice, cats, and dogs. How bind enter host cells is still incompletely understood. Recently, type I transmembrane protein CD300lf was identified murine norovirus receptor, yet it unclear how virus capsid receptor interact at molecular level. In this study, we determined X-ray crystal structure soluble (sCD300lf) protruding domain complex a 2.05-Å resolution. We...

Recent reports suggest that human genogroup II genotype 17 (GII.17) noroviruses are increasing in prevalence. We analyzed the evolutionary changes of three GII.17 capsid protruding (P) domains. found P domains had little cross-reactivity with antisera raised against dominant GII.4 strains. X-ray structural analysis from 2002 to 2014 and 2015 suggested surface-exposed substitutions on uppermost part domain might have generated a novel 2014-2015 variant.

Molecular surfaces are the key players in biomolecular recognition and interactions. Nowadays, it is trivial to visualize a molecular surface surface-distributed properties three-dimensional space. However, such representation trends be biased ambiguous case of thorough analysis. We present new method create 2D spherical projection maps entire protein manipulate with them—protein topography (PST). It permits visualization thoughtful analysis properties. PST helps easily portray...

The discovery of vulnerable regions on norovirus particles is instrumental in the development effective inhibitors, particularly for GI noroviruses that are genetically diverse. Analysis these GI.1-specific Nanobodies has shown similar to GII particles, have regions. only known cofactor region, HBGA binding pocket, represents main target inhibition. With a combination treatment, i.e., addition Nano-7 or Nano-94 with 2′FL, effect inhibition was increased. Therefore, drug treatments might...

To gain success in the evolutionary "arms race," venomous animals such as scorpions produce diverse neurotoxins selected to hit targets nervous system of prey. Scorpion α-toxins affect insect and/or mammalian voltage-gated sodium channels (Na(v)s) and thereby modify excitability muscle nerve cells. Although more than 100 are known a number them have been studied into detail, molecular mechanism their interaction with Na(v)s is still poorly understood. Here, we employ extensive dynamics...

Typically, human noroviruses cause symptoms of acute gastroenteritis for 2 to 4 days. Often, the virions are shed in stool several days after recede, which turn can lead further contamination and transmission. Moreover, a number reports have considered that chronic norovirus infections, i.e., lasting months years, might even function as reservoirs generation novel strains escape herd immunity or modified binding interactions with histo-blood group antigens (HBGAs). In this study, we analyzed...

Noroviruses are the leading cause of outbreaks acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which considered essential cofactors for norovirus infection. This study structurally characterizes nanobodies developed against clinically important GII.4 and GII.17 noroviruses a focus on identification novel that efficiently block HBGA binding site. Using X-ray crystallography, we have characterized nine different bound to top, side, or bottom P...

This research discovered and analyzed two different types of MNV-neutralizing nanobodies. The top-binding nanobodies sterically inhibited the receptor-binding site, whereas dimeric-binding interfered with a structural modification associated cofactor binding. Moreover, we found that capsid contained number vulnerable regions were essential for viral replication. In fact, appeared to be organized in state flux, which could important cofactor/receptor-binding functions. Blocking these...

To investigate the effect of two ways lipofuscin production (lipid peroxidation and glycation) on fluorescence characteristics phototoxicity to compare them with properties natural lipofuscin.Model lipofuscins were prepared basis bovine photoreceptor outer segments (POS) bisretinoid A2E addition. One set samples was from POS modified by lipid peroxidation, while another glycation fructose. Fluorescent kinetics photoinduced superoxide generation model human retinal pigment epithelium (RPE)...

Temporal changes in the GII.4 human norovirus capsid sequences occasionally result emergence of genetic variants capable causing new epidemics. The persistence is believed to be associated with recognition numerous histo-blood group antigen (HBGA) types and antigenic drift. We found that one earliest known isolate (1974) a more recent epidemic variant (2012) had varied norovirus-specific monoclonal antibody (MAb) reactivities, yet similar HBGA binding profiles. To better understand...

Bovine meat and milk factors (BMMFs) are circular, single-stranded episomal DNAs that have been detected in bovine products. BMMFs thought to roles human malignant degenerative diseases. encode a replication initiator protein (Rep) is actively transcribed translated cells. In this study, Rep WH1 domain encoded on BMMF (MSBI1.176) isolated from multiple sclerosis brain sample was determined 1.53 Å resolution using X-ray crystallography. The overall structure of the MSBI1.176 remarkably...