Introduction: Neutralizing antibodies have been approved for coronavirus disease 2019 (COVID-19) treatment; however, no study has clarified the link among their neutralizing effect in vitro, the period of infectious virus shedding, and symptoms in the acute phase. Here, we aimed to assess the duration of virus shed and fever in patients with mild COVID-19 stratified by their characteristics and type of neutralizing antibody administered.
Methods: We evaluated the efficacy of neutralizing antibodies in terms of the duration of infectious virus excretion and fever in three groups: patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta strain treated with REGEN-CoV2 (REGN-CoV2 group) and patients infected with Omicron strain treated with S309 (S309 group) or untreated (untreated group).
Monoclonal antibody (mAb) technology has significantly contributed to basic research and clinical settings for various purposes, including protective and therapeutic drugs. However, a rapid and convenient method to generate high-affinity antigen-specific mAbs has not yet been reported. Here, we developed a rapid, easy, and low-cost protocol for antigen-specific mAb production from single memory B cells.
View Article and Find Full Text PDFProkaryotes organize intracellular compartments with protein-based organelles called encapsulins. Encapsulins with icosahedral symmetry can encapsulate specific cargo proteins mediated by targeting peptides or encapsulation-mediating domains. Encapsulins have been used in eukaryotic cells for bioengineering, vaccine development, and nanoparticle alignment.
View Article and Find Full Text PDFWe prepared polyoxomolybdates with methylammonium countercations from methylammonium monomolybdate, (CHNH)[MoO], through two dehydrative condensation methods, acidifying in the aqueous solution and solid-state heating. Discrete (CHNH)[MoO(OH)(HO)], polymeric ((CHNH)[MoO(HO)]), and polymeric ((CHNH)[γ-MoO]) were selectively isolated via pH control of the aqueous (CHNH)[MoO] solution. The HSO-acidified solution of pH < 1 produced "sulfonated α-MoO", polymeric ((CHNH)[(MoO)(SO)]).
View Article and Find Full Text PDFChlorous acid water (HClO2) is known for its antimicrobial activity. In this study, we attempted to accurately assess the ability of chlorous acid water to inactivate SARS-CoV-2. When using cell culture supernatants of infected cells as the test virus, the 99% inactivation concentration (IC99) for the SARS-CoV-2 D614G variant, as well as the Delta and Omicron variants, was approximately 10ppm of free chlorine concentration with a reaction time of 10 minutes.
View Article and Find Full Text PDFWe first investigated the interactions between several algae-derived lectins and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We created lectin columns using high-mannose (HM)-type glycan-specific lectins OAA and KAA-1 or core fucose-specific lectin hypninA-2 and conducted binding experiments with SARS-CoV-2. The results showed that these lectins were capable of binding to the virus.
View Article and Find Full Text PDFThe immune evasion of SARS-CoV-2 Omicron variants caused by multiple amino acid replacements in the receptor-binding domain (RBD) of the spike protein wanes the effectiveness of antibodies elicited by current SARS-CoV-2 booster vaccination. The vaccines that target Omicron strains have been recently developed, however, there has been a concern yet to be addressed regarding the negative aspect of the immune response known as original antigenic sin. Here, we demonstrate that the breadth of neutralizing antibodies against SARS-CoV-2 variants is barely elicited by immunizing monovalent viral antigens via vaccination or natural infection in mice and human subjects.
View Article and Find Full Text PDFThe solid-state thermal structure transformation of methylammonium vanadate, (CHNH)VO, from -150 °C to 350 °C is reported. Variable-temperature X-ray single-crystal structure analysis at 23, 0, -50, -100, and -150 °C reveal (CHNH)VO comprises of methylammonium cations and "snake-like" ([VO]) anion chains propagating along the -direction in the 2 space group. In between -150 and -100 °C, we observe a reversible structural transformation due to the re-orientation of the methylammonium cations in the crystal packing, which is also confirmed by the reversible profiles observed in differential scanning calorimetry.
View Article and Find Full Text PDFEthanol is an effective disinfectant against the novel coronavirus SARS-CoV-2. However, its effective concentration has not been shown, and we therefore analyzed the effects of different concentrations of ethanol on SARS-CoV-2. When SARS-CoV-2 was treated with varying ethanol concentrations and examined for changes in infectivity, the ethanol concentration at which 99% of the infectious titers were reduced was 24.
View Article and Find Full Text PDFAn influenza virus epidemic is an important issue in public hygiene, and continuous development on an effective drug is required. Kampo medicine is a traditional medicine that is used clinically for treatment of various diseases in Japan and other East Asian countries. We evaluated the effects of the Kampo drugs maoto, kakkonto, senkyuchachosan, jinkokato, and bakumondoto, which are prescribed for treatment of respiratory symptoms including symptoms caused by influenza, on influenza virus replication in cultured cells.
View Article and Find Full Text PDFThe possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization.
View Article and Find Full Text PDFThe enzyme 5,10-methylenetetrahydrofolate dehydrogenase (MTHFD) is essential for the production of certain amino acids (glycine, serine, and methionine) and nucleic acids (thymidylate and purine). Here, we identified a cDNA encoding this enzyme from the silkworm . The recombinant MTHFD (bmMTHFD) expressed in recognized 5,10-methylenetetrahydrofolate and 5,10-methenyltetrahydrofolate as substrate in the presence of NADP as well as NAD .
View Article and Find Full Text PDFNearly all viruses of the Reoviridae family possess a multi-layered capsid consisting of an inner layer with icosahedral T = 1 symmetry and a second-outer layer (composed of 260 copies of a trimeric protein) exhibiting icosahedral T = 13 symmetry. Here we describe the construction and structural evaluation of an assembly intermediate of the Rice dwarf virus of the family Reoviridae stalled at the second capsid layer via targeted disruption of the trimer-trimer interaction interface in the second-layer capsid protein. Structural determination was performed by conventional and Zernike/Volta phase-contrast cryoelectron microscopy.
View Article and Find Full Text PDFPreviously, we found an unclassified glutathione S-transferase 2 (bmGSTu2) in the silkworm Bombyx mori that conjugates glutathione to 1-chloro-2,4-dinitrobenzene and also metabolises diazinon, an organophosphate insecticide. Here, we provide a structural and genome-editing characterisation of the diazinon-metabolising glutathione S-transferase in B. mori.
View Article and Find Full Text PDFRice dwarf virus (RDV) of the family Reoviridae and genus Phytoreovirus, is the cause of rice dwarf disease, a major negative effector of rice production throughout East Asia, including Japan. RDV has an icosahedral double-layered shell of approximately 70 nm diameter. The structural proteins constituting the capsid can self-assemble into a correct particle without requiring the help of any external factors in vitro.
View Article and Find Full Text PDFProstaglandins are involved in many physiological processes, and prostaglandin synthases facilitate the detoxification of xenobiotics as well as endogenous compounds, such as through glutathione conjugation. Specifically, prostaglandin D synthase (PGDS) catalyzes the isomerization of PGH to PGD. Here we report the identification and structural analysis of PGDS from the brown planthopper rice pest Nilaparvata lugens (nlPGDS), which belongs to the sigma-class glutathione transferases.
View Article and Find Full Text PDFSingle particle diffractive imaging data from Rice Dwarf Virus (RDV) were recorded using the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS). RDV was chosen as it is a well-characterized model system, useful for proof-of-principle experiments, system optimization and algorithm development. RDV, an icosahedral virus of about 70 nm in diameter, was aerosolized and injected into the approximately 0.
View Article and Find Full Text PDFWe report a new member of the aldo-keto reductase (AKR) superfamily in the silkworm Bombyx mori. Based on its amino acid sequence, the new enzyme belongs to the AKR2 family and was previously assigned the systematic name AKR2E5. In the present study, recombinant AKR2E5 was expressed, purified to homogeneity, and characterized.
View Article and Find Full Text PDFThe minor outer capsid protein P2 of Rice dwarf virus (RDV), a member of the genus Phytoreovirus in the family Reoviridae, is essential for viral cell entry. Here, we clarified the structure of P2 and the interactions to host insect cells. Negative stain electron microscopy (EM) showed that P2 proteins are monomeric and flexible L-shaped filamentous structures of ∼20 nm in length.
View Article and Find Full Text PDFGlutathione transferases (GSTs) are a major class of detoxification enzymes that play a central role in the defense against environmental toxicants and oxidative stress. Here, we studied the crystal structure of a delta-class glutathione transferase from Nilaparvata lugens, nlGSTD, to gain insights into its catalytic mechanism. The structure of nlGSTD in complex with glutathione, determined at a resolution of 1.
View Article and Find Full Text PDFRNase Po1 is a guanylic acid-specific ribonuclease member of the RNase T1 family from Pleurotus ostreatus. We previously reported that RNase Po1 inhibits the proliferation of human tumor cells, yet RNase T1 and other T1 family RNases are non-toxic. We determined the three-dimensional X-ray structure of RNase Po1 and compared it with that of RNase T1.
View Article and Find Full Text PDFRecently, many technical improvements in macromolecular X-ray crystallography have increased the number of structures deposited in the Protein Data Bank and improved the resolution limit of protein structures. Almost all high-resolution structures have been determined using a synchrotron radiation source in conjunction with cryocooling techniques, which are required in order to minimize radiation damage. However, optimization of cryoprotectant conditions is a time-consuming and difficult step.
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