Heparin Precursors with Reduced Anticoagulant Properties Retain Antiviral and Protective Effects That Potentiate the Efficacy of Sofosbuvir against Zika Virus Infection in Human Neural Progenitor Cells.

Pagani, Isabel ORCID: 0000-0001-5396-0740, Ottoboni, Linda, Panina-Bordignon, Paola ORCID: 0000-0001-9913-8568, Martino, Gianvito, Poli, Guido ORCID: 0000-0001-7241-4526, Taylor, Sarah, Turnbull, Jeremy E ORCID: 0000-0002-1791-754X, Yates, Edwin ORCID: 0000-0001-9365-5433 and Vicenzi, Elisa (2023) Heparin Precursors with Reduced Anticoagulant Properties Retain Antiviral and Protective Effects That Potentiate the Efficacy of Sofosbuvir against Zika Virus Infection in Human Neural Progenitor Cells. Pharmaceuticals (Basel, Switzerland), 16 (10). 1385-.

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Official URL: http://dx.doi.org/10.3390/ph16101385

Abstract

Zika virus (ZIKV) infection during pregnancy can result in severe birth defects, such as microcephaly, as well as a range of other related health complications. Heparin, a clinical-grade anticoagulant, is shown to protect neural progenitor cells from death following ZIKV infection. Although heparin can be safely used during pregnancy, it retains off-target anticoagulant effects if directly employed against ZIKV infection. In this study, we investigated the effects of chemically modified heparin derivatives with reduced anticoagulant activities. These derivatives were used as experimental probes to explore the structure-activity relationships. Precursor fractions of porcine heparin, obtained during the manufacture of conventional pharmaceutical heparin with decreased anticoagulant activities, were also explored. Interestingly, these modified heparin derivatives and precursor fractions not only prevented cell death but also inhibited the ZIKV replication of infected neural progenitor cells grown as neurospheres. These effects were observed regardless of the specific sulfation position or overall charge. Furthermore, the combination of heparin with Sofosbuvir, an antiviral licensed for the treatment of hepatitis C (HCV) that also belongs to the same Flaviviridae family as ZIKV, showed a synergistic effect. This suggested that a combination therapy approach involving heparin precursors and Sofosbuvir could be a potential strategy for the prevention or treatment of ZIKV infections.

Item Type:	Article
Uncontrolled Keywords:	Zika virus, combination therapy, heparin, heparin derivatives, heparin precursor fractions, protective effects
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Dec 2023 11:34
Last Modified:	13 Dec 2023 11:34
DOI:	10.3390/ph16101385
Open Access URL:	https://doi.org/10.3390/ph16101385
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3177338