In vitro and in vivo anti-HMPV activity of JH001 isolated from Chinese medicinal herbs / 中国药理学与毒理学杂志

OBJECTIVE Human metapneumovirus (hMPV) is semblable to respiratory syncytial virus (RSV) which causes respiratory infections typically characterized by cough, runny nose, fever, and nasal congestion but sometimes progressing to bronchiolitis and pneumonia. Whereas, there is no corresponding drug to inhabit the virus. Studies of new compounds with potential anti-HMPV activity could produce clinical value. Chinese herbal medicine played a great role during COVID-19, therefore we choose some small molecular (JH001) extracted from botany to investigate therapeutic effect on hMPV and the underlying mechanisms. METHODS In this study, 16HBE cells were used as a model to explore in vitro antiviral effect. Cytotoxicity assays were performed before the antiviral tests, cell viability of 16HBE cells handled by different concentration of JH001 was estimated by Cell Counting Kit-8 (CCK-8). Then RT-qPCR, immunofluores?cence, and flow cytometer were used to test the viral titer after cells infected with hMPV. Eventually, 6-8 weeks mice were infected intranasally with 60 μL of hMPV, the control group was treated with 0.9％ saline water, other groups were administered with JH001 and ribavirin, then the lung virus titer and protective effect in lung were judged. RESULTS The obtained JH001 exhibited no cytotoxicity to 16HBE cells during 6.25 - 200 μmol · L-1. RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline. And fluo?rescence exhibited distinct decrease of hMPV-N protein, flow cytometer results showed that MFI decrease evidently. Sig?nificant reduction of N-gene expression was observed in those mice treated with JH001 compared with saline group, which indicated that JH001 probably had protective and therapeutic effect on viral replication. CONCLUSION This study illustrated that JH001 might be a promising option for small molecular against hMPV and JH001 might be worthy of fur?ther development and used as a potential therapeutic strategy for other respiratory viruses in the future.

Prevalencia del virus de la rinotraqueitis infecciosa bovina en el departamento del Caquetá, Amazonía Colombiana / Prevalence of bovine infectious rhinotracheitis virus in Caquetá department, Colombian Amazon

RESUMEN La rinotraqueitis infecciosa bovina (IBR) es una enfermedad ampliamente difundida en el mundo con gran repercusión socio-económica en las ganaderías bovinas. El objetivo del presente estudio fue determinar la prevalencia de IBR en 100 hatos del departamento del Caquetá, para lo cual, se muestrearon 960 bovinos mayores de 36 meses entre enero y marzo de 2016 en predios seleccionados a partir de los criterios: a) tamaño (50-180 hectáreas), b) con más de 10 vacas en ordeño, c) disponibilidad de los productores para cooperar y d) accesibilidad de las vías. Las muestras de suero sanguíneo se remitieron al Laboratorio de Diagnóstico Clínico Veterinario del ICA y se analizaron a través la prueba Elisa de bloqueo (BHV-1) gB. Los sueros con porcentaje de bloqueo superior al 55% se consideraron positivos a anticuerpos para IBR. Se encontró alta seroprevalencia (73,13%), mayor además en machos que en hembras (p < 0,05). A nivel municipal la seroprevalencia fue mayor en los municipios de El Doncello, Puerto Rico y San Vicente del Caguán y se encontró diferencia significativa (p < 0,05) entre los nueve municipios analizados. A nivel de hatos, la prevalencia fue del 99%. En conclusión, la prevalencia del virus de la rinotraqueitis infecciosa bovina (IBR) en bovinos de doble propósito del departamento del Caquetá fue muy alta.

ABSTRACT Infectious bovine rhinotracheitis (IBR) is a disease widely spread throughout the world with great socio-economic impact on bovine livestock. The objective of this study was to determine the prevalence of IBR in 100 herds in Caqueta department, for which 960 cattle older than 36 months between January and March 2016 were sampled in farms selected from the criteria: a) size (50-180 hectares), b) with more than 10 cows in milking, c) availability of producers to cooperate and d) accessibility of roads. Blood serum samples were sent to the ICA veterinary clinical diagnostic laboratory and analyzed using the Elisa blocking test (BHV-1) gB, where sera with blocking percentage greater than 55% were considered as positive for IBR antibodies. High seroprevalence was found (73.13%), being higher in males than in females (p < 0.05). At municipal level, seroprevalence was greater in El Doncello, Puerto Rico and San Vicente del Caguán municipalities, significant difference (p<0.05) was found between the nine municipalities analyzed. At herd level prevalence was of 99%. In conclusion the prevalence of Infectious Bovine Rhinotracheitis (IBR) virus in dual-purpose cattle of Caquetá department was very high.

A medium-throughput screen for inhibitors of human metapneumovirus.

Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed vaccines or drugs for human metapneumovirus. We developed a fluorescent, cell-based medium-throughput screening assay for human metapneumovirus that captures inhibitors of all stages of the viral lifecycle except budding of progeny virus particles from the cell membrane. We optimized and validated the assay and performed a successful medium-throughput screening. A number of hits were identified, several of which were confirmed to inhibit viral replication in secondary assays. This assay offers potential to discover new antivirals for human metapneumovirus and related respiratory viruses. Compounds discovered using the medium-throughput screening may also provide useful probes of viral biology.

Human metapneumovirus in paediatric intensive care unit (PICU) admissions in the United Kingdom (UK) 2006-2014.

BACKGROUND: Human metapneumovirus (HMPV) is a pneumovirus known to cause respiratory disease in children. It was identified as a pathogen in 2001 and its healthcare burden and associated costs are not fully understood. OBJECTIVES: This study aimed to assess the clinical characteristics of children with HMPV infection admitted to paediatric intensive care units (PICUs) across the United Kingdom (UK) over a nine-year period and to estimate the associated costs of care. STUDY DESIGN: Data were collected from the UK paediatric intensive care audit network (PICANet) and costs calculated using the National Health Service (NHS) reference costing scheme. RESULTS: There were 114 admissions in which HMPV was detected. The number of admissions associated with a code of HMPV rose steadily over the study period (three in 2006 to 28 in 2014) and showed significant seasonal variability, with the peak season being from November to May. Children required varying levels of intensive care support from minimal to complex support including invasive ventilation, inotropes, renal replacement therapy and extracorporeal membrane oxygenation (ECMO). HMPV was associated with five deaths during the study period. The associated costs of PICU admissions were estimated to be between £2,256,823 and £3,997,823 over the study period, with estimated annual costs rising over the study period due to increasing HMPV admissions. CONCLUSIONS: HMPV is associated with a significant healthcare burden and associated cost of care in PICUs in the UK.

Vaccines for the Paramyxoviruses and Pneumoviruses: Successes, Candidates, and Hurdles.

Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children within the first few years of life and are the etiologic agents for many serious acute respiratory illnesses. These virus infections are also associated with long-term diseases that impact quality of life, including asthma. Despite over a half-century of vaccine research, development, and clinical trials, no vaccine has been licensed to date for the paramyxoviruses or pneumoviruses for the youngest infants. In this study, we describe the recent reclassification of paramyxoviruses and pneumoviruses into distinct families by the International Committee on the Taxonomy of Viruses. We also discuss some past unsuccessful vaccine trials and some currently preferred vaccine strategies. Finally, we discuss hurdles that must be overcome to support successful respiratory virus vaccine development for the youngest children.

Current developments and prospects on human metapneumovirus vaccines.

INTRODUCTION: Human metapneumovirus (hMPV) has become one of the major pathogens causing acute respiratory infections (ARI) mainly affecting young children, immunocompromised patients, and the elderly. Currently there are no licensed vaccines against this virus. Areas covered: Since the discovery of hMPV in 2001, many groups have focused on developing vaccines against this pathogen. This review presents the outcomes and perspectives derived from preclinical studies performed in cell cultures and animals as well as the only candidate that has reached evaluation in a clinical trial. Limitations of the current vaccine candidates are discussed and perspectives for the development of plant-based vaccines are analyzed. Expert commentary: Several hMPV vaccine candidates are under development with the potential to progress into clinical trials. In parallel, the molecular farming field offers new opportunities to generate innovative vaccines that will offer several advantages in the fight against hMPV.

Role of dietary antioxidants in human metapneumovirus infection.

Human metapneumovirus (hMPV) is a major cause of respiratory tract infections in children, elderly and immunocompromised hosts, for which no vaccine or treatment are currently available. Oxidative stress and inflammatory responses represent important pathogenic mechanism(s) of hMPV infection. Here, we explored the potential protective role of dietary antioxidants in hMPV infection. Treatment of airway epithelial cells with resveratrol and quercetin during hMPV infection significantly reduced cellular oxidative damage, inflammatory mediator secretion and viral replication, without affecting viral gene transcription and protein synthesis, indicating that inhibition of viral replication occurred at the level of viral assembly and/or release. Modulation of proinflammatory mediator expression occurred through the inhibition of transcription factor nuclear factor (NF)-κB and interferon regulatory factor (IRF)-3 binding to their cognate site of endogenous gene promoters. Our results indicate the use of dietary antioxidants as an effective treatment approach for modulating hMPV induced lung oxidative damage and inflammation.