A5083922647- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- SARS-CoV-2 detection and testing
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Malaria Research and Control
- Immunotherapy and Immune Responses
- Viral Infections and Outbreaks Research
- Virology and Viral Diseases
- Insect symbiosis and bacterial influences
- HIV Research and Treatment
- Influenza Virus Research Studies
- Respiratory viral infections research
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Bacterial Infections and Vaccines
- vaccines and immunoinformatics approaches
- interferon and immune responses
- Long-Term Effects of COVID-19
- Telomeres, Telomerase, and Senescence
- Viral Infections and Immunology Research
The University of Queensland
2016-2025
Global Virus Network
2025
Australian e-Health Research Centre
2022-2024
Institute of Bioengineering and Nanotechnology
2022
Austral University of Chile
2020
Mahidol University
2010-2013
Complications arising from dengue virus infection include potentially fatal vascular leak, and severe disease has been linked with excessive immune cell activation. An understanding of the triggers this activation is critical for development appropriately targeted control strategies. We show here that secreted form nonstructural protein 1 (NS1) a pathogen-associated molecular pattern (PAMP). Highly purified NS1 devoid bacterial endotoxin activity directly activated mouse macrophages human...
Abstract The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed understand such divergent clinical outcomes. Here we show analysis coronavirus antibody responses pre-pandemic healthy children ( n = 89), adults 98), 57), patients 50) systems serology. Moderate levels cross-reactive, but non-neutralizing, antibodies...
Abstract The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that despite large size of viral RNA genome (~30 kb), infectious full-length cDNA readily assembled in vitro a circular polymerase extension reaction (CPER) methodology without need for technically demanding intermediate steps. Overlapping fragments are generated from and together with linker fragment containing CMV promoter into single reaction. Transfection...
Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases probable Parkinson's disease. As microglial NLRP3 inflammasome activation major driver neurodegeneration, here we interrogated whether promote activation. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) as COVID-19 pre-clinical model,...
Heparan sulfate (HS) is a cell surface polysaccharide recently identified as coreceptor with the ACE2 protein for S1 spike on SARS-CoV-2 virus, providing tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have anticoagulant and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), cancer drug candidate, binds destabilizes receptor binding domain directly inhibits its to ACE2,...
RNA metagenomic analysis of tissues from 4 wild-caught northern short-tailed shrews in Alabama, USA, revealed a novel henipavirus (family Paramyxoviridae). Phylogenetic supported the placement virus within shrew clade, related to human-infecting shrewborne henipaviruses. Our study results highlight presence infections North America.
We have found that dengue virus (DENV) not only uses preexisting enhancing antibodies to promote its entry into Fc receptor-bearing cells but also exploits for intracellular immune evasion through 2 mechanisms. In the first mechanism, of DENV-antibody complexes human monocytic activates negative regulators, dihydroxyacetone kinase and autophagy-related 5-autophagy-related 12, which then disrupt retinoic acide incucible gene I melanoma differentiation associated 5 signaling cascade disable...
Insect-specific Binjari virus facilitates the production of chimeric particles flavivirus pathogens for diagnostics and vaccines.
Two antibodies against flaviviruses Flaviviruses are a group of RNA viruses that include the human pathogens dengue virus, Zika and West Nile virus. The envelope protein (E) on virus surface has been target vaccine development, but problems have arisen with E, leading to enhanced infection. Now, Modhiran et al. Biering describe two different bind flavivirus NS1 prevent it from disrupting epithelial cells, which is associated severe disease. Both cross-react multiple proteins. reduce viremia...
The secreted hexameric form of the dengue virus (DENV) non-structural protein 1 (NS1) has recently been shown to elicit inflammatory cytokine release and disrupt endothelial cell monolayer integrity. This suggests that circulating NS1 contributes vascular leak plays a major role in pathology haemorrhagic fever shock. Pathways activated by are thus great interest as potential therapeutic targets. Recent works have separately implicated both toll-like receptor 4 (TLR4) TLR2/6 heterodimer...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been identified as the causative agent of coronavirus disease 2019 and is capable human-to-human transmission rapid global spread. The emergence spread SARS-CoV-2 encouraged establishment a rapid, sensitive, reliable viral detection quantification methodology. Here, we present an alternative assay, termed immuno-plaque assay (iPA), which utilizes combination plaque immunofluorescence techniques. We have extensively optimized...
Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) linked to severe neurological manifestations. Senescent cells contribute brain aging, but the impact of virus-induced senescence on neuropathologies unknown. Here we show that senescent accumulate in aged human organoids senolytics reduce age-related inflammation rejuvenate transcriptomic aging clocks. In postmortem brains patients with COVID-19 observed increased cell accumulation compared...
Chimeric orthoflaviviruses derived from the insect-specific Binjari virus (BinJV) offer a promising basis for safe orthoflavivirus vaccines. However, these vaccines have so far only been produced using adherent C6/36 Aedes albopictus mosquito cell cultures grown in serum-supplemented media, limiting their scalable manufacture. To address this, we adapted cells serum-free suspension culture Sf900-III medium, achieving high peak densities (up to 2.5 × 107 cells/mL). Higher agitation rates...
Background The phenomenon of antibody dependent enhancement as a major determinant that exacerbates disease severity in DENV infections is well accepted. While the detailed mechanism enhanced unclear, evidence suggests it associated with both increased infectivity and suppression type I IFN pro-inflammatory cytokine responses. Therefore, imperative for us to understand intracellular mechanisms altered during ADE infection decipher severe pathogenesis. Methodology/Principal Findings In this...
Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through manufacturability vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia).A panel recombinant Sclamp proteins were produced Chinese hamster ovary screened vitro select lead candidate. The structure this was...
The structure of an infectious immature flavivirus redefines viral architecture and maturation.
Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order reduce the burden placed on health systems, situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required meet demand: recombinant antibodies fulfill these requirements have marked clinical potential. Here, we describe fast-tracked development of an alpaca Nanobody specific for receptor-binding-domain (RBD) Spike protein with potential therapeutic...
A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing HEK293T cells with SARS-CoV-2 and do not find virus integrated genome. By examining ONT data from separate cultivars, completely resolve 78 L1 insertions...
Abstract The epidemic emergence of relatively rare and geographically isolated flaviviruses adds to the ongoing disease burden viruses such as dengue. Structural analysis is key understand combat these pathogens. Here, we present a chimeric platform based on an insect-specific flavivirus for safe rapid structural pathogenic viruses. We use this approach resolve architecture two neurotropic structure dengue virus at 2.5 Å, highest resolution enveloped virion. These reconstructions allow...
Abstract In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This is closely related to Mòjiāng (MojV), and both are divergent the bat-borne HNV members, Nipah (NiV) Hendra (HeV) viruses. The spillover of LayV first instance zoonosis humans outside NiV HeV, highlighting continuing threat this genus poses human health. work, we determine prefusion structures MojV F proteins via cryogenic electron microscopy...
Abstract In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus (JEV) caused an unprecedented and widespread outbreak disease in pigs humans Australia. As no veterinary vaccines against JEV are approved Australia all current human derived from (G) III strains, we used the recently described insect-specific Binjari (BinJV) chimeric flavivirus vaccine technology to produce GIV candidate. Herein describe production displaying structural prM E proteins isolate obtained stillborn...