prikaz prve stranice dokumenta Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers
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Scientific paper - Original scientific paper
Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers
Pharmaceutics, 15 (2023), 12; 2680. https://doi.org/10.3390/pharmaceutics15122680
Wild, Markus; Karner, Dubravka; Eickhoff, Jan; Wagner, Sabrina; Kicuntod, Jintawee; Chang, William; Barry, Peter; Jonjić, Stipan; Lenac Roviš, Tihana; Marschall, Manfred

Institutional repository: Repository of the University of Rijeka, Faculty of Medicine

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Wild, M., Karner, D., Eickhoff, J., Wagner, S., Kicuntod, J., Chang, W. ... Marschall, M. (2023). Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers. Pharmaceutics, 15. (12). doi: 10.3390/pharmaceutics15122680

Wild, Markus, et al. "Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers." Pharmaceutics, vol. 15, no. 12, 2023. https://doi.org/10.3390/pharmaceutics15122680

Wild, Markus, Dubravka Karner, Jan Eickhoff, Sabrina Wagner, Jintawee Kicuntod, William Chang, Peter Barry, Stipan Jonjić, Tihana Lenac Roviš and Manfred Marschall. "Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers." Pharmaceutics 15, no. 12 (2023). https://doi.org/10.3390/pharmaceutics15122680

Wild, M., et al. (2023) 'Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers', Pharmaceutics, 15(12). doi: 10.3390/pharmaceutics15122680

Wild M, Karner D, Eickhoff J, Wagner S, Kicuntod J, Chang W, and sur.. Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers. Pharmaceutics [Internet]. 2023 November 27 [cited 2024 May 14];15(12). doi: 10.3390/pharmaceutics15122680

M. Wild, et al., "Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers", Pharmaceutics, vol. 15, no. 12, November 2023. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:023389. [Accessed: 14 May 2024]

Metadata
Title (english)Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers
AuthorMarkus Wild
AuthorDubravka Karner
AuthorJan Eickhoff
AuthorSabrina Wagner
AuthorJintawee Kicuntod
AuthorWilliam Chang
AuthorPeter Barry
AuthorStipan Jonjić
AuthorTihana Lenac Roviš
AuthorManfred Marschall
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Center for Proteomics)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Abstract (english)
Despite the availability of currently approved antiviral drugs, infections with human cytomegalovirus (HCMV) still cause clinically challenging, sometimes life-threatening situations. There is an urgent need for enhanced anti-HCMV drugs that offer improved efficacy, reduced dosages and options for long-term treatment without risk of the development of viral drug resistance. Recently, we reported the pronounced anti-HCMV efficacy of pharmacological inhibitors of cyclin-dependent kinases (CDKs), in particular, the potential of utilizing drug synergies upon combination treatment with inhibitors of host CDKs and the viral CDK-like kinase pUL97 (vCDK/pUL97). Here, we expand this finding by further assessing the in vitro synergistic antiviral interaction between vCDK and CDK inhibitors towards HCMV as well as non-human cytomegaloviruses. An extension of this synergy approach was achieved in vivo by using the recombinant MCMV-UL97/mouse model, confirming the high potential of combination treatment with the clinically approved vCDK inhibitor maribavir (MBV) and the developmental CDK7 inhibitor LDC4297. Moreover, mechanistic aspects of this synergistic drug combination were illustrated on the levels of intracellular viral protein transport and viral genome replication. The analysis of viral drug resistance did not reveal resistance formation in the case of MBV + LDC4297 combination treatment. Spanning various investigational levels, these new results strongly support our concept, employing the great potential of anti-HCMV synergistic drug treatment.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionPublished version
Journal titlePharmaceutics
Numberingvol. 15, no. 12, 2680
e-ISSN1999-4923
DOIhttps://doi.org/10.3390/pharmaceutics15122680
URN:NBNurn:nbn:hr:184:023389
Publication2023-11-27
Document URLhttps://www.mdpi.com/1999-4923/15/12/2680
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2023-11-29 09:29:22