A5043094102- SARS-CoV-2 and COVID-19 Research
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- vaccines and immunoinformatics approaches
- Enzyme Structure and Function
- COVID-19 Clinical Research Studies
- Heat shock proteins research
- Computational Drug Discovery Methods
- Viral Infections and Immunology Research
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- RNA Research and Splicing
- Synthesis and biological activity
- Vector-borne infectious diseases
- Helicobacter pylori-related gastroenterology studies
- Lymphoma Diagnosis and Treatment
- DNA Repair Mechanisms
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Signaling Pathways in Disease
- Mosquito-borne diseases and control
The University of Melbourne
2022-2024
Australian Regenerative Medicine Institute
2018-2024
Monash University
2018-2024
Discovery Institute
2021-2022
Institute of Molecular Biology, Academia Sinica
2012-2017
National Defense Medical Center
2012-2016
Academia Sinica
2012-2016
The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with increase mortality and morbidity. Here we report our modelled homo-trimer structure spike glycoprotein both closed (ligand-free) open (ligand-bound) conformation, which involved host cell adhesion. We also predict the unique N- O-linked glycosylation sites that distinguish it from SARS underlines shielding camouflage defence system. Furthermore, study highlights key finding S1 domain...
The COVID-19 pandemic is an urgent global health emergency, and the presence of Furin site in SARS-CoV-2 spike glycoprotein alters virulence warrants further molecular, structural, biophysical studies. Here we report structure complex with glycoprotein, demonstrating how binds to S1/S2 region eventually cleaves viral protein using experimental functional studies, molecular dynamics, docking. structural studies underline mechanism mode action Furin, which a key process host cell entry...
SARS-CoV-2 is the cause of ongoing Coronavirus disease 19 (COVID-19) pandemic around world causing pneumonia and lower respiratory tract infections. In understanding pathogenicity mechanism action, it essential to depict full repertoire expressed viral proteins. The recent biological studies have highlighted leader protein Nsp1 importance in shutting down host production. Besides, still enigmatic how regulates for translation. Here we report novel structure from complex with SL1 region 5'UTR...
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has infected more than 520 million people around the globe resulting in 6.2 as of May 2022. Understanding cell entry mechanism SARS-CoV-2 and its entire repertoire is a high priority for developing improved therapeutics. spike glycoprotein (S-protein) engages with host receptor ACE2 adhesion serine proteases furin TMPRSS2 proteolytic activation subsequent entry. Recent studies have...
The conserved, ATP-dependent bacterial DnaK chaperones process client substrates with the aid of co-chaperones DnaJ and GrpE. However, in absence structural information, how these proteins communicate each other cannot be fully delineated. For study reported here, we solved crystal structure a full-length Geobacillus kaustophilus HTA426 GrpE homodimer complex nearly G. that contains interdomain linker (acting as pseudo-substrate), N-terminal nucleotide-binding C-terminal substrate-binding...
BACKGROUND The worldwide COVID-19 pandemic is increasing exponentially and demands an effective promising therapy at most emergency. METHODS We have assembled a cohort consisting 504 hospitalized patients. Detailed information on patients’ characteristics antiviral medication use during their stay designated hospitals along with pre post treatment results were collected. study objective to evaluate the efficacy of Arbidol, together concurrent drugs Oseltamivir Lopinavir/Ritonavir mortality...
This study employed a ligand-based pharmacophoric approach to design and synthesize 33 novel semisynthetic labdane-appended triazolyl isatins discover potential anti-inflammatory agents. The efficacy of the derivatives was evaluated by their ability inhibit production NO, TNF-α, IL-6, in lipopolysaccharide-induced RAW264.7 macrophages. initial screening revealed that compound 7a ((1-(2-(2,3-dioxoindolin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl...
Abstract The poliovirus type I IRES is able to recruit ribosomal machinery only in the presence of host factor PCBP2 that binds stem–loop IV IRES. When cleaved its linker region by viral proteinase 3CD, translation initiation ceases allowing next stage replication commence. Here, we investigate interaction with apical (SLIVm) RNA full-length and truncated form. CryoEM structure reconstruction complex SLIVm solved 6.1 Å resolution reveals a compact globular interacting cruciform via KH...
Coxiella burnetii is an obligate zoonotic bacterium that targets macrophages causing a disease called Q fever. It has biphasic developmental life cycle where the extracellular and metabolically inactive small cell variant (SCV) transforms inside host into vegetative large (LCV). However, details about morphological structural changes of this transition are still lacking. Here, we used cryo-electron tomography to image both SCV LCV variants grown either under axenic conditions or purified...
Abstract Disease-causing mutations in genes encoding transcription factors (TFs) can affect TF interactions with their cognate DNA-binding motifs. Whether and how impact upon the binding to composite elements (CE) interaction other TFs is unclear. Here, we report a distinct mechanism of alteration human lymphomas perturbed B cell identity, particular classic Hodgkin lymphoma. It caused by recurrent somatic missense mutation c.295 T > C (p.Cys99Arg; p.C99R) targeting center domain...
Helicobacter pylori encodes homologues of PilM, PilN and PilO from bacteria with Type IV pili, where these proteins form a pilus alignment complex. Inactivation pilO changes H. motility in semi-solid media, suggesting link to the chemosensory pathways or flagellar motor. Here, we showed that mutation pilN gene strain SS1 reduced mean linear swimming speed liquid implicating function, regulation of, We also demonstrated soluble variants share common biochemical properties their pili...
Abstract SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 activation and entry. With aid whole-exome sequencing, we report variant rs12329760 in gene its mutant V160M, which might impede viral Furthermore, identified cleavage sites S2 domain structure complex with glycoprotein. We also structures protease inhibitors TMPRSS2, could hamper interaction protein. These...
Bacterial ribonucleotide reductases (RNRs) play an important role in the synthesis of dNTPs and their expression is regulated by transcription factors, NrdR Fur. Recent transcriptomic studies using deletion mutants have indicated a for bacterial chemotaxis maintenance topoisomerase levels. However, alone has no effect on growth or virulence infected flies human blood cells. Furthermore, are limited to strain alone, so inadequate drawing biological implications when repressor active abundant....
The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 and perpetual rise of new variants warrant investigation molecular structural details infection process modulation host defense viral proteins. This Letter reports combined experimental computational approaches to provide key insights into functional basis Nsp1's association with different cyclophilins FKBPs in regulating COVID-19 infection. We demonstrated real-time stability dynamics Nsp1-CypA/FKBP1A complex...
Prolonged inflammation leads to the genesis of various inflammatory diseases such as atherosclerosis, cancer, bowel disease, Alzheimer's, etc. The uncontrolled response is characterized by excessive release pro-inflammatory mediators nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1alpha (IL-1α), and enzymes cyclooxygenase-2 (COX-2). Hence, downregulation these an active therapy control aberrant tissue damage. To address this, herein, we present...
The DnaB primosomal protein from Gram-positive bacteria plays a key role in DNA replication and restart as loader for the recruitment of replisome cascade proteins. Previous investigations have established that is composed an N-terminal domain, middle C-terminal domain. However, structural evidence how functions at atomic level lacking. Here, we report crystal structure DnaB, encompassing domains (residues 1–300), Geobacillus stearothermophilus (GstDnaB1–300) 2.8 Å resolution. Our revealed...
Trehalose-6-phosphate hydrolase (TreA) belongs to glycoside family 13 (GH13) and catalyzes the hydrolysis of trehalose 6-phosphate (T6P) yield glucose 6-phosphate. The products this reaction can be further metabolized by energy-generating glycolytic pathway. Here, crystal structures Bacillus licheniformis TreA ( Bl TreA) its R201Q mutant complexed with p -nitrophenyl-α-D-glucopyranoside (R201Q– PNG) are presented at 2.0 2.05 Å resolution, respectively. overall structure is similar those...
Stress granules are non-membrane bound RNA-protein essential for survival during acute cellular stress. TIA-1 is a key protein in the formation of stress that undergoes liquid-liquid phase separation by association with specific RNAs and protein-protein interactions. However, fundamental properties enable phase-separation also render susceptible to irreversible fibrillar aggregates. Despite this, within physiological granules, not present as fibrils, pointing additional factors cell prevent...