Shunsuke Kita
A5085189861- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- T-cell and B-cell Immunology
- Bacteriophages and microbial interactions
- Immunotherapy and Immune Responses
- Transgenic Plants and Applications
- HIV Research and Treatment
- Viral Infections and Immunology Research
- Viral Infectious Diseases and Gene Expression in Insects
- HIV/AIDS drug development and treatment
- RNA modifications and cancer
- Silkworms and Sericulture Research
- Reproductive System and Pregnancy
- SARS-CoV-2 detection and testing
- Cancer-related gene regulation
- Genomics and Phylogenetic Studies
- Insect Resistance and Genetics
- Bacillus and Francisella bacterial research
- Heat shock proteins research
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
Hokkaido University
2016-2025
Hokkaido Pharmaceutical University
2015-2024
Drug Discovery Laboratory (Norway)
2022
Fracture Analysis Consultants (United States)
2017
Instituto Superior Técnico
2011
In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that emerged through recombination of two cocirculating BA.2 lineages, BJ.1 BM.1.1.1 (a progeny BA.2.75), during summer 2022. XBB.1 variant most profoundly resistant to BA.2/5 breakthrough infection sera date more fusogenic than BA.2.75. The breakpoint located in receptor-binding domain spike, each region recombinant spike confers...
The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. is a BA.2 descendant but phylogenetically distinct from BA.5, the currently predominant descendant. Here, we show that has greater effective reproduction number and different immunogenicity profile than BA.5. We determined sensitivity of to vaccinee convalescent sera as well panel clinically available antiviral drugs antibodies. Antiviral largely retained potency, antibody varied depending on several key BA.2.75-specific...
Abstract Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence XBB.1.5, a new Variant Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring S486P spike (S) mutation, subsequent to acquisition nonsense mutation ORF8. Neutralization assays showed similar abilities immune escape between and XBB.1. We determine structural basis for interaction human ACE2 S protein showing overall structures proteins XBB.1.5. provide intrinsic pathogenicity...
Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but variability of RBS epitopes hampers broad neutralization multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV variants. X-ray crystallography revealed coordinated recognition by heavy chain non-RBS conserved sites light binding angle mimicking...
Abstract In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron XBB, EG.5.1 (a progeny XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures experimental animals, use human sera antiviral compounds, reveal virological features newly emerging...
Abstract In middle-late 2023, a sublineage of SARS-CoV-2 Omicron XBB, EG.5.1 (a progeny XBB.1.9.2), is spreading rapidly around the world. Here, we performed multiscale investigations to reveal virological features newly emerging variant. Our phylogenetic-epidemic dynamics modeling suggested that two hallmark substitutions EG.5.1, S:F456L and ORF9b:I5T, are critical increased viral fitness. Experimental addressing growth kinetics, sensitivity clinically available antivirals, fusogenicity...
Summary Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence XBB.1.5, a new Variant Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring F486P spike (S) mutation, subsequent to acquisition nonsense mutation ORF8. Neutralization assays showed similar abilities immune escape between and XBB.1. We determined structural basis for interaction human ACE2 S protein showing overall structures proteins XBB.1.5. The intrinsic pathogenicity hamsters...
SARS-CoV-2 Omicron subvariants have evolved to evade receptor-binding site (RBS) antibodies that exist in diverse individuals as public antibody clones. We rationally selected RBS resilient mutations emerging subvariants. Y489 was identified a of virus vulnerability and common footprint broadly neutralizing against the Multiple Y489-binding were encoded by clonotypes additionally recognized F486, potentially accounting for emergence harboring F486V mutation. However, subclass neutralized...
<title>Abstract</title> Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a threat to public health and the economy. Although several SARS-CoV-2 vaccines exist, they have failed elicit effective neutralizing antibody responses against emerging variants harboring spike protein mutations. Moreover, while certain neutralizing-antibody-based therapies were in early stages of pandemic, their performance declined with emergence Thus, it is...
Signal transducer and activator of transcription (STAT) family members mediate signaling in the Janus kinase (JAK)–STAT pathway are activated by phosphorylation at a conserved tyrosine residue, resulting dimerization through reciprocal interactions between phosphotyrosine Src homology 2 (SH2) domain. Tyrosine-phosphorylated STAT (pY-STAT) then translocates to nucleus induce expression genes encoding antiviral proteins. Although active functional forms STATs conventionally considered be...
Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for severity of COVID-19 patients. We previously reported an antibody, NT-108 with activity. However, structural and functional basis activity has not yet been understood. Here, we demonstrated therapeutic effects a hamster model its protective at low doses. Furthermore, determined cryo-EM structure complex spike. The single-chain Fv...
Human leukocyte Ig-like receptors (LILR) LILRB1 and LILRB2 are immune checkpoint that regulate a wide range of physiological responses by binding to diverse ligands, including HLA-G. HLA-G is exclusively expressed in the placenta, some immunoregulatory cells, tumors has several unique isoforms. However, recognition isoforms LILRs poorly understood. In this study, we characterized LILR β2-microglobulin (β2m)-free HLA-G1 isoform, which synthesized placental trophoblast cells tends dimerize...
Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts up-conformation. However, whether also interacts with RBD down-conformation facilitate conformational shift RBD-up remains unclear. Herein, we present structures of BA.2.86 JN.1 proteins bound ACE2. Notably, successfully observed ACE2-bound down-RBD, indicating an...
ABSTRACT Mumps virus (MuV) infection induces formation of cytoplasmic inclusion bodies (IBs). Growing evidence indicates that IBs are the sites where RNA viruses synthesize their viral RNA. However, in case MuV infection, little is known about and cellular compositions biological functions IBs. In this study, pulldown purification N-terminal amino acid sequencing revealed stress-inducible heat shock protein 70 (Hsp72) was a binding partner phosphoprotein (P protein), which an essential...
Many potent neutralizing SARS-CoV-2 antibodies have been developed and used for therapies. However, the effectiveness of many has reduced against recently emerging variants, especially Omicron variant. We identified a highly antibody, UT28K, in COVID-19 convalescent individuals who recovered from severe condition. UT28K showed efficacy an
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), known to occur annually. Because no virus-specific fully effective treatments against these many other viruses have been approved, there is an urgent need for novel, therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum...
The CD1d protein is a nonpolymorphic MHC class I-like that controls the activation of natural killer T (NKT) cells through presentation self- and foreign-lipid ligands, glycolipids, or phospholipids, leading to secretion various cytokines. contains large hydrophobic lipid binding pocket: A′ pocket CD1d, which recognizes moieties such as long fatty acyl chains. Although lipid–protein interactions typically rely on between chains sites proteins, we showed small polar regions located deep...
Emerging evidence has revealed the pivotal roles of C-type lectin-like receptors (CTLRs) in regulation a wide range immune responses. Human natural killer cell receptor-P1A (NKRP1A) is one CTLRs and recognizes another CTLR, transcript 1 (LLT1) on target cells to control NK, NKT Th17 cells. The structural basis for NKRP1A-LLT1 interaction was limitedly understood. Here, we report crystal structure ectodomain LLT1. plausible receptor-binding face domain flat, forms an extended β-sheet....
Abstract Understanding the molecular properties of SARS-CoV-2 is crucial to tackle future outbreaks. Current knowledge trimeric spike protein relies on truncated recombinant proteins and inactivated full-length forms, which may suffer from overstabilization. Here, we apply cryo-electron tomography (cryo-ET) at a Biosafety level 3 facility study virus structure in its native, active state. The particles show variable shapes with diffusible spikes, majority typical prefusion conformations....
Venomous snakes have endogenous proteins that neutralize the toxicity of their venom components. We previously identified five small serum (SSP-1-SSP-5) from a highly venomous snake belonging to family Viperidae as inhibitors various toxins venom. The belong prostate secretory protein 94 amino acids (PSP94) family. SSP-2 interacts with triflin, which is member cysteine-rich (CRISP) blocks smooth muscle contraction. However, structural basis for interaction and biological roles these are...
The human immunodeficiency virus (HIV) accessory protein Nef plays a major role in establishing and maintaining infection, particularly through immune evasion. Many HIV-2-infected people experience long-term viral control survival, resembling HIV-1 elite control. HIV-2 has overlapping but also distinct functions from Nef. Here we report the crystal structure of core. di-leucine sorting motif forms helix bound to neighboring molecules, moreover, isothermal titration calorimetry demonstrated...