In Silico Pharmacology, Journal Year: 2024, Volume and Issue: 12(2)
Published: Aug. 2, 2024
Language: Английский
Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(741)
Published: April 3, 2024
No licensed vaccines or therapies exist for patients infected with Nipah virus (NiV), although an experimental human monoclonal antibody (mAb) cross-reactive to the NiV and Hendra (HeV) G glycoprotein, m102.4, has been tested in a phase 1 trial provided under compassionate use both HeV exposures. is highly pathogenic zoonotic paramyxovirus causing regular outbreaks humans animals South Southeast Asia. The mortality rate of infection ranges from 40% more than 90%, making it substantial public health concern. glycoprotein mediates host cell attachment, F facilitates membrane fusion infection. We hypothesized that mAb against prefusion conformation may confer better protection m102.4. To test this, two potent neutralizing mAbs protein, hu1F5 hu12B2, were compared hamster model. Hu1F5 superior hu12B2 was selected comparison m102.4 ability protect African green monkeys (AGMs) stringent challenge. AGMs exposed intranasally Bangladesh strain treated 5 days after exposure either (25 milligrams per kilogram). Whereas only one six survived until study end point, all protected. Furthermore, reduced 10 kilogram dose also complete challenge, supporting upcoming clinical advancement this postexposure prophylaxis therapy.
Language: Английский
Citations
11
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: April 6, 2024
Abstract Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 NiV42) targeting NiV receptor binding protein (RBP) were identified. Following affinity maturation, derived from NiV41 display cross-reactivity against both Hendra (HeV), whereas antibody based on NiV42 only specific to NiV. Results immunogenetic analysis reveal correlation between maturation their antiviral activity. In vivo testing its mature form (41-6) show protective efficacy lethal challenge in hamsters. Furthermore, 2.88 Å Cryo-EM structure tetrameric RBP complex demonstrates that 41-6 blocks interface. These findings can be beneficial development design vaccines with broad spectrum henipaviruses.
Language: Английский
Citations
10
Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 171 - 171
Published: Jan. 24, 2024
Nipah virus (NiV), a biosafety level 4 agent, was first identified in human clinical cases during an outbreak 1998 Malaysia and Singapore. While flying foxes are the primary host viral vector, infection is associated with severe presentation humans, resulting high mortality rate. Therefore, NiV considered elevated epidemic potential which further underscored by its recent emergence (September 2023) as India. Given situation, it paramount to understand molecular dynamics of shed more light on evolution prevent future outbreaks. In this study, we conducted Bayesian phylogenetic analysis all available complete genomes, including partial N-gene sequences (≥1000 bp) public databases since case, registered 1998. We observed distribution genomes into three main clades corresponding genotypes Malaysia, Bangladesh India, Malaysian clade being oldest evolutionary terms. The skyline plot showed increase population size 2019. Protein presence specific protein families (Hendra_C) bats that might keep asymptomatic state bats, also serve vectors. Our results indicate shortage would be instrumental gaining better understanding NiV’s preventing investigation underscores critical need strengthen genomic surveillance based will aid thorough genetic characterization circulating strains relationships between henipaviruses. This approach prepare us tackle challenges posed other emerging viruses.
Language: Английский
Citations
6
Iranian Journal of Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 12, 2024
Background and Objectives: Multiple outbreaks over two decades a high mortality rate have emphasized the Nipah virus (NiV) as priority research area. The study focuses on identifying mutational landscape in sequences from NiV human isolates different geographical regions. Materials Methods: Thirty-seven genomes of samples Malaysia, Bangladesh, India were subject- ed to phylogeny metagenomic analysis decipher genome variability using MEGA11 software meta-CATS web server. Using Single-Likelihood Ancestor Counting method, synonymous nonsynonymous mutations among genes identified. Further, variations used identify all proteins. Results: categorized into NiV-M, NiV-B, NiV-I clades based phylogenetic analysis. Metag- enomic revealed 1636 noncoding coding regions three NiV. Further showed phosphoprotein be highly mutating, whereas matrix protein was stable. Conclusion: Deciphering mutation pattern comparative genomics approach for provided valuable insight stability proteins which can further understanding host-pathogen interaction developing effective therapeutic measures.
Language: Английский
Citations
4
New Microbes and New Infections, Journal Year: 2023, Volume and Issue: 56, P. 101195 - 101195
Published: Nov. 11, 2023
Language: Английский
Citations
9
Antiviral Research, Journal Year: 2024, Volume and Issue: 233, P. 106046 - 106046
Published: Dec. 3, 2024
RNA viruses present a constant threat to human health, often with limited options for vaccination or therapy. Notable examples include influenza and coronaviruses, which have pandemic potential. Filo- henipaviruses cause more outbreaks, but high case fatality rates. All rely on the activity of virus-encoded RNA-dependent polymerase (RdRp). An antiviral nucleoside analogue, 4'-Fluorouridine (4'-FlU), targets RdRp diminishes replication several viruses, including A virus SARS-CoV-2, through incorporation into nascent viral delayed chain termination. However, effective concentration 4'-FlU varied among different raising need fortify its efficacy. Here we show that inhibitors dihydroorotate dehydrogenase (DHODH), an enzyme essential pyrimidine biosynthesis, can synergistically enhance effect against henipaviruses, Ebola virus. Even 4'-FlU-resistant mutant was re-sensitized towards by DHODH inhibition. The addition uridine rescued replication, strongly suggesting depletion as mechanism this synergy. also highly SARS-CoV-2 in hamster model COVID. We propose impairment endogenous synthesis inhibition enhances RNAs. This strategy may be broadly applicable efficacy analogues
Language: Английский
Citations
3
Protein Science, Journal Year: 2025, Volume and Issue: 34(4)
Published: March 18, 2025
The Hendra (HeV) and Nipah (NiV) viruses are high-priority, biosafety level-4 pathogens that cause fatal neurological respiratory disease. Their P gene encodes not only the protein, an essential polymerase cofactor, but also virulence factors V W. We previously showed W protein of HeV (WHeV) forms amyloid-like fibrils one its subdomains, PNT3, fibrillates in isolation. However, fibrillation kinetics is much faster case full-length WHeV compared to suggesting another region contributes process. In this work, we identified spanning residues 2-110 (PNT1) as crucial implicated fibrillation. Through site-directed mutagenesis, combined with thioflavin T binding experiments negative-staining transmission electron microscopy, a predicted cryptic amyloidogenic (CAR) within PNT1 main driver deciphered underlying molecular mechanism. Using FTIR, enriched cross β-sheets. Sequence alignment revealed conservation CAR across Henipavirus genus enabled identification hitherto never reported pro-amyloidogenic motif. ability form was experimentally shown be common property shared by proteins. Overall, study sheds light on mechanisms calls for future studies aimed at exploring relevance newly motif valuable target antiviral approaches.
Language: Английский
Citations
0
Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 428 - 428
Published: April 18, 2025
Background: The emergence of several paramyxoviruses, including Nipah virus (NiV), makes continued efforts in vaccine development as part pandemic preparedness necessary. Although NiV is a zoonotic pathogen with high case fatality, there still no licensed vaccine. Methods: Herein, attachment glycoprotein G (NiV-G), which crucial to host cell receptor binding, was used develop epitope-based peptide vaccines. A total 39 B- and T-cell epitopes NiV-G were shortlisted for synthesis evaluation using silico analysis. Results: vitro antigenicity the candidates showed eight synthesized peptides (G7, stalk-domain epitopes) relatively binding antibody-positive serum (A450nm: 1.39–3.78). Moreover, nine-mer (9-mer) found be less reactive than their longer counterparts (15–30 aa, G7-1, G7-4), but 9-mer activity enhanced cyclization (NPLPFREYK, A450nm: 2.66) C-terminal amidation modification (NPLPFREYK-NH2, 1.39). Subsequently, vivo validation immunized mice revealed immunogenicity potential G7-1 (30 NENVNEKCKFTLPPLKIHECNISCPNPLPF) elicit strong antigen-specific antibody response against homologous antigen (I.V., 1.48 ± 0.78; I.M., 1.66 0.66). However, recombinant protein remained low, suggesting limited recognition native antigen. Conclusions: This study focused on preliminary screening vaccines single formulations minimal modifications candidates. Our findings collectively show immunogenic stalk-based epitope novel therapeutic underscores need strategic design, delivery, formulation optimization enhance its protective efficacy translational application.
Language: Английский
Citations
0
Advances in virus research, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
0
Hygiene, Journal Year: 2025, Volume and Issue: 5(2), P. 18 - 18
Published: May 2, 2025
In recent decades, the world has observed emergence and re-emergence of a multitude previously non-existent or re-emerging infectious diseases, for which there is paucity timely effective preventative measures. The WHO published catalogue priority pathogens that are likely to trigger future epidemics, with objective designing prophylactic therapeutic interventions. rationale behind these interventions rooted in comprehensive understanding aetiology, epidemiology, pathogenesis target diseases. While it imperative acknowledge pivotal role evolutionary changes play, equally important recognise influence multifaceted interplay factors on These include human populations, vectors reservoirs exposure, environmental changes. This review summarises ten as well those high epidemic potential already focus specific control programme initiatives, such HIV/AIDS, tuberculosis, malaria Furthermore, this concentrated means addressing infections through public health surveillance response systems. Such systems must be designed rapidly detect unusual unexpected disease patterns, track share information real time, mobilise global responses, most ways effectively contain transmission.
Language: Английский
Citations
0