A protectin DX (PDX) analog with in vitro activity against influenza A(H1N1) viruses.

antiviral agents cell cultures influenza virus pathogenesis research and analysis methods respiratory tract virus classification

Journal

Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876

Informations de publication

Date de publication:
Mar 2024
Historique:
revised: 25 01 2024
received: 09 11 2023
accepted: 08 02 2024
medline: 25 2 2024
pubmed: 25 2 2024
entrez: 25 2 2024
Statut: ppublish

Résumé

Antiviral therapy based on neuraminidase (oseltamivir) or polymerase (baloxavir marboxil) inhibitors plays an important role in the management of influenza infections. However, the emergence of drug resistance and the uncontrolled inflammatory response are major limitations in the treatment of severe influenza disease. Protectins D1 (PD1) and DX (PDX), part of a family of pro-resolving mediators, have previously demonstrated anti-influenza activity as well as anti-inflammatory properties in various clinical contexts. Herein, we synthetized a series of simplified PDX analogs and assessed their in vitro antiviral activity against influenza A(H1N1) viruses, including oseltamivir- and baloxavir-resistant variants. In ST6GalI-MDCK cells, the PDX analog AN-137B reduced viral replication in a dose-dependent manner with IC

Identifiants

pubmed: 38402600
doi: 10.1002/jmv.29484
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e29484

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

© 2024 Wiley Periodicals LLC.

Références

Iuliano AD, Roguski KM, Chang HH, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391(10127):1285-1300.
Bui C, Bethmont A, Chughtai AA, et al. A systematic review of the comparative epidemiology of avian and human influenza A H5N1 and H7N9 - lessons and unanswered questions. Transbound Emerg Dis. 2016;63(6):602-620.
Krammer F, Smith GJD, Fouchier RAM, et al. Influenza. Nat Rev Dis Primers. 2018;4(1):3.
Liu Q, Zhou Y, Yang Z. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol. 2016;13(1):3-10.
Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database Syst Rev. 2014;2014(4):CD008965.
Principi N, Camilloni B, Alunno A, Polinori I, Argentiero A, Esposito S. Drugs for influenza treatment: is there significant news? Front Med. 2019;6:109.
Omoto S, Speranzini V, Hashimoto T, et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep. 2018;8(1):9633.
Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913-923.
Liu C, Hu L, Dong G, et al. Emerging drug design strategies in anti-influenza drug discovery. Acta Pharm Sin B. 2023;13(12):4715-4732.
Hansen TV, Vik A, Serhan CN. The protectin family of specialized pro-resolving mediators: potent immunoresolvents enabling innovative approaches to target obesity and diabetes. Front Pharmacol. 2019;9:1582.
Xia H, Chen L, Liu H, et al. Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype. Sci Rep. 2017;7(1):99.
Rajasagi NK, Reddy PBJ, Mulik S, Gjorstrup P, Rouse BT. Neuroprotectin D1 reduces the severity of herpes simplex virus-induced corneal immunopathology. Invest Opthalmol Vis Sci. 2013;54(9):6269-6279.
Walker KH, Krishnamoorthy N, Brüggemann TR, Shay AE, Serhan CN, Levy BD. Protectins PCTR1 and PD1 reduce viral load and lung inflammation during respiratory syncytial virus infection in mice. Front Immunol. 2021;12:704427.
Morita M, Kuba K, Ichikawa A, et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell. 2013;153(1):112-125.
Imai Y. Role of omega-3 PUFA-derived mediators, the protectins, in influenza virus infection. Biochim Biophys Acta Mol Cell Biol Lipids. 2015;1851(4):496-502.
Marette A, Maltais R, Poirier DTotal syntheses of specialized pro-resolving mediators (SPMs), structural isomers and structural analogs Canada2022
Hatakeyama S, Sakai-Tagawa Y, Kiso M, et al. Enhanced expression of an α2,6-Linked sialic acid on MDCK cells improves isolation of human influenza viruses and evaluation of their sensitivity to a neuraminidase inhibitor. J Clin Microbiol. 2005;43(8):4139-4146.
Neumann G, Ozawa M, Kawaoka Y. Reverse genetics of influenza viruses. Methods Mol Biol. 2012;865:193-206.
Abed Y, Tu V, Carbonneau J, et al. Comparison of early and recent influenza A(H1N1)pdm09 isolates harboring or not the H275Y neuraminidase mutation, in vitro and in animal models. Antiviral Res. 2018;159:26-34.
Checkmahomed L, M'Hamdi Z, Carbonneau J, et al. Impact of the Baloxavir-Resistant polymerase acid I38T substitution on the fitness of contemporary influenza A(H1N1)pdm09 and A(H3N2) strains. J Infect Dis. 2020;221(1):63-70.
Maltais R, Sancéau JY, Poirier D, Marette A. A concise, gram-scale total synthesis of protectin DX and related labeled versions via a key stereoselective reduction of enediyne. J Org Chem. 2023;88(11):7088-7095.
Checkmahomed L, Padey B, Pizzorno A, et al. In vitro combinations of baloxavir acid and other inhibitors against seasonal influenza A viruses. Viruses. 2020;12(10):1139.
Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-681.
de León P, Cañas-Arranz R, Bustos MJ, Sáiz M, Sobrino F. Inhibition of human coronaviruses by combinations of Host-Targeted and Direct-Acting antivirals. Antimicrob Agents Chemother. 2023;67(4):e0170322.
White PJ, Arita M, Taguchi R, Kang JX, Marette A. Transgenic restoration of long-chain n-3 fatty acids in insulin target tissues improves resolution capacity and alleviates obesity-linked inflammation and insulin resistance in high-fat-fed mice. Diabetes. 2010;59(12):3066-3073.
Kawaguchi N, Koshimichi H, Ishibashi T, Wajima T. Evaluation of drug-drug interaction potential between baloxavir marboxil and oseltamivir in healthy subjects. Clin Drug Invest. 2018;38(11):1053-1060.

Auteurs

Nicolas Fortin (N)

Research Center in Infectious Diseases, CHU de Québec-Université Laval, Quebec City, Canada.

Mathilde Hénaut (M)

Research Center in Infectious Diseases, CHU de Québec-Université Laval, Quebec City, Canada.

Nathalie Goyette (N)

Research Center in Infectious Diseases, CHU de Québec-Université Laval, Quebec City, Canada.

René Maltais (R)

Medicinal Chemistry Platform, CHU de Québec-Université Laval, Quebec City, Canada.

Jean-Yves Sancéau (JY)

Medicinal Chemistry Platform, CHU de Québec-Université Laval, Quebec City, Canada.

André Marette (A)

Medicinal Chemistry Platform, CHU de Québec-Université Laval, Quebec City, Canada.

Donald Poirier (D)

Medicinal Chemistry Platform, CHU de Québec-Université Laval, Quebec City, Canada.

Yacine Abed (Y)

Research Center in Infectious Diseases, CHU de Québec-Université Laval, Quebec City, Canada.

Guy Boivin (G)

Research Center in Infectious Diseases, CHU de Québec-Université Laval, Quebec City, Canada.

Classifications MeSH