المؤلفون: Rota, Paola, La Rocca, Paolo, Bonfante, Francesco, Pagliari, Matteo, Cirillo, Federica, Piccoli, Marco, Ghiroldi, Andrea, Franco, Valentina, Pappone, Carlo, Allevi, Pietro, Anastasia, Luigi

المساهمون: P. Rota, P. La Rocca, F. Bonfante, M. Pagliari, F. Cirillo, M. Piccoli, A. Ghiroldi, V. Franco, C. Pappone, P. Allevi, L. Anastasia

مصطلحات موضوعية: human parainfluenza virus 1, sialic acid, antiviralinhibitor, hemagglutinin-neuraminidase, viral infection, Settore BIO/10 - Biochimica

الوصف: In the search for effective antivirals against Paramyxoviridae, the dynamics of human parainfluenza virus type 1 hemagglutinin-neuraminidase (hPIV1-HN) inhibition offers a promising perspective. This study focuses on the potential of C5- and C4-modified 2,3-unsaturated sialic acid (DANA) inhibitors and highlights their interaction with the hPIV1-HN enzyme. We show that a strategic substitution, replacing the C5 isopropyl group in BCX 2798 with a trifluoroacetyl function, increases inhibitory potency 3- to 4-fold. At the same time, we explore the special properties of the catalytic site of hPIV1-HN, which harbors only small substituents and favors a C4 sulfonyl-amido function over a carbonyl function, in contrast to the C4 pocket of Newcastle disease virus hemagglutinin-neuraminidase (NDV-HN). Based on these findings, we present a newly identified potent inhibitor that has the preferred C5 trifluoro-acetamido and C4 trifluoro-sulfonyl-amide groups. The results of this study pave the way for a deeper understanding of the C4 and C5 binding pockets of hPIV1-HN and promote the development of new, more selective inhibitors.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37849540; info:eu-repo/semantics/altIdentifier/wos/WOS:001072718400001; volume:14; issue:10; firstpage:1383; lastpage:1388; numberofpages:6; journal:ACS MEDICINAL CHEMISTRY LETTERS; https://hdl.handle.net/2434/1032216Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85174969463

الإتاحة: https://doi.org/10.1021/acsmedchemlett.3c00291Test
https://hdl.handle.net/2434/1032216Test

المؤلفون: Michael Welch, Karen Krueger, Jianqiang Zhang, Megan Neveau, Pablo Piñeyro, Drew Magstadt, Rodger Main, Phillip Gauger

المصدر: Veterinary Sciences, Vol 10, Iss 1, p 18 (2022)

مصطلحات موضوعية: porcine parainfluenza virus 1, human parainfluenza virus 1, Paramyxoviridae, Respirovirus, strain comparison, pathogenesis, Veterinary medicine, SF600-1100

الوصف: Porcine parainfluenza virus 1 (PPIV1) is a newly characterized porcine respiratory virus. Recent experimental challenge studies in three-week-old nursery pigs failed to cause disease. However, it remains unclear how genetic differences contribute to viral pathogenesis. To characterize the pathogenesis of different PPIV1 isolates, three-week-old nursery pigs were challenged with either PPIV1 isolate USA/MN25890NS/2016 (MN16) or USA/IA84915LG/2017 (IA17). A human parainfluenza virus 1 (HPIV1) strain C35 ATCC® VR-94™ was included to evaluate swine as a model for human parainfluenza. All viruses were successfully re-isolated from bronchoalveolar lavage fluid and detected by RT-qPCR at necropsy. Microscopic lung lesions were more severe in the IA17 group compared to the non-challenged negative control (Ctrl) group whereas differences were not found between the MN16 and Ctrl groups. Immunohistochemistry staining in respiratory samples showed a consistent trend of higher levels of PPIV1 signal in the IA17 group followed by the MN16 group, and no PPIV1 signal observed in the HPIV1 or Ctrl groups. This study suggests potential pathogenesis differences between PPIV1 isolates. Additionally, these results indicate that HPIV1 is capable of replicating in nursery pigs after experimental inoculation. However, clinical disease or gross lung lesions were not observed in any of the challenge groups.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2306-7381/10Test/1/18; https://doaj.org/toc/2306-7381Test

الوصول الحر: https://doaj.org/article/dcb4e6f716c542b4bd4f515275097768Test

المؤلفون: Fieldhouse J.K., Toh T.-H., Lim W.-H., Ting J., Ha S.-J., Hii K.-C., Kong C.-I., Wong T.-M., Wong S.-C., Warkentien T.E., Gray G.C.

المساهمون: DUKE-NUS MEDICAL SCHOOL

المصدر: Unpaywall 20191101

مصطلحات موضوعية: adolescent, adult, Article, child, cross-sectional study, human, Human parainfluenza virus 1, Human parainfluenza virus 2, Human parainfluenza virus 3, Human parainfluenza virus 4, Human respiratory syncytial virus, Human respiratory syncytial virus A, Human respiratory syncytial virus B, infant, infection risk, major clinical study, Malaysia, molecular diagnosis, nonhuman, Paramyxovirinae, pilot study, pneumonia, prevalence, real time polymerase chain reaction, reverse transcription polymerase chain reaction, risk factor, throat culture, virus identification, classification, female

الوصف: 10.1371/journal.pone.0202147 ; PLoS ONE ; 13 ; 8 ; e0202147

العلاقة: Fieldhouse J.K., Toh T.-H., Lim W.-H., Ting J., Ha S.-J., Hii K.-C., Kong C.-I., Wong T.-M., Wong S.-C., Warkentien T.E., Gray G.C. (2018). Surveillance for respiratory syncytial virus and parainfluenza virus among patients hospitalized with pneumonia in Sarawak, Malaysia. PLoS ONE 13 (8) : e0202147. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0202147Test; https://scholarbank.nus.edu.sg/handle/10635/161240Test

الإتاحة: https://doi.org/10.1371/journal.pone.0202147Test
https://scholarbank.nus.edu.sg/handle/10635/161240Test

المؤلفون: Linster, M, Do, L.A.H, Minh, N.N.Q, Chen, Y, Zhe, Z, Tuan, T.A, Tuan, H.M, Su, Y.C.F, Van Doorn, H.R, Moorthy, M, Smith, G.J.D

المساهمون: DUKE-NUS MEDICAL SCHOOL

المصدر: Unpaywall 20200831

مصطلحات موضوعية: acute disease, adolescent, chi square distribution, child, female, follow up, genetic variation, genetics, human, Human parainfluenza virus 1, Human parainfluenza virus 2, Human parainfluenza virus 3, Human parainfluenza virus 4, infant, male, molecular epidemiology, newborn, nonparametric test, phylogeny, preschool child, procedures, real time polymerase chain reaction, respiratory tract infection, Respirovirus infection, severity of illness index, Viet Nam, virus genome, whole genome sequencing, Chi-Square Distribution, Preschool

الوصف: 10.1038/s41598-018-24767-4 ; Scientific Reports ; 8 ; 1 ; 6833

العلاقة: Linster, M, Do, L.A.H, Minh, N.N.Q, Chen, Y, Zhe, Z, Tuan, T.A, Tuan, H.M, Su, Y.C.F, Van Doorn, H.R, Moorthy, M, Smith, G.J.D (2018). Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1-4 in Children from Viet Nam. Scientific Reports 8 (1) : 6833. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-24767-4Test; https://scholarbank.nus.edu.sg/handle/10635/174224Test

الإتاحة: https://doi.org/10.1038/s41598-018-24767-4Test
https://scholarbank.nus.edu.sg/handle/10635/174224Test

المصدر: Testing of Respiratory Specimens for the Validation of the QIAGEN ResPlex II Advanced Panel Test and the Artus Influenza A/B RT-PCR Test

الوصول الحر: https://clinicaltrials.gov/ct2/show/NCT01302418Test

المؤلفون: Henrickson, Kelly J.

المصدر: The Journal of Infectious Diseases, 1991 Dec 01. 164(6), 1128-1134.

الوصول الحر: https://www.jstor.org/stable/30111744Test

المؤلفون: Ambrose, M. R., Hetherington, S. V., Watson, A. S., Scroggs, R. A., Portner, A.

المصدر: The Journal of Infectious Diseases, 1995 Apr 01. 171(4), 851-856.

الوصول الحر: https://www.jstor.org/stable/30132171Test

المؤلفون: Henrickson, Kelly J., Savatski, Laura L.

المصدر: The Journal of Infectious Diseases, 1992 Nov 01. 166(5), 995-1005.

الوصول الحر: https://www.jstor.org/stable/30113369Test

المؤلفون: Hetherington, Seth V., Watson, Ann S., Scroggs, Ruth A., Portner, Allen

المصدر: The Journal of Infectious Diseases, 1994 Feb 01. 169(2), 248-252.

الوصول الحر: https://www.jstor.org/stable/30113900Test

المؤلفون: Bartlett, E. J., Hennessey, M., Skiadopoulos, M. H., Schmidt, A. C., Collins, P. L., Murphy, B. R., Pickles, R. J.

المصدر: Journal of Virology, 82(16)

مصطلحات موضوعية: Human parainfluenza virus 1, Voie respiratoire, Interferon, Virology, Virologie, Epithelium, Mutación, Epitelio, Respiratory tract, Replication, Paramyxovirinae, Virus, Cytokine, Paramyxovirus, Mutation, Réplication, Parainfluenza virus humain 1, Homme, Interféron, Mononegavirales, Replicación, Citoquina, Paramyxoviridae, Human, Epithélium, Virología, Vía respiratoria

الوصف: Human parainfluenza virus type 1 (HPIV1) is a significant cause of pediatric respiratory disease in the upper and lower airways. An in vitro model of human ciliated airway epithelium (HAE), a useful tool for studying respiratory virus-host interactions, was used in this study to show that HPIV1 selectively infects ciliated cells within the HAE and that progeny virus is released from the apical surface with little apparent gross cytopathology. In HAE, type I interferon (IFN) is induced following infection with an HPIV1 mutant expressing defective C proteins with an F170S amino acid substitution, rHPIV1-CF170S, but not following infection with wild-type HPIV1. IFN induction coincided with a 100- to 1,000-fold reduction in virus titer, supporting the hypothesis that the HPIV1 C proteins are critical for the inhibition of the innate immune response. Two recently characterized live attenuated HPIV1 vaccine candidates expressing mutant C proteins were also evaluated in HAE. The vaccine candidates, rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710-11, which contain temperature-sensitive (ts) attenuating (att) and non-ts att mutations, were highly restricted in growth in HAE at permissive (32°C) and restrictive (37°C) temperatures. The viruses grew slightly better at 37°C than at 32°C, and rHPIV1-CR84G/Δ170HNT553ALY942A was less attenuated than rHPIV1-CR84G/Δ170HNT553ALΔ1710-11. The level of replication in HAE correlated with that previously observed for African green monkeys, suggesting that the HAE model has potential as a tool for the preclinical evaluation of HPIV1 vaccines, although how these in vitro data will correlate with vaccine virus replication in seronegative human subjects remains to be seen.

العلاقة: https://doi.org/10.17615/h9c0-hf76Test; https://cdr.lib.unc.edu/downloads/mc87pz71c?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/mc87pz71cTest

الإتاحة: https://doi.org/10.17615/h9c0-hf76Test
https://cdr.lib.unc.edu/downloads/mc87pz71c?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/mc87pz71cTest