Publication Database

Inhibition of herpes simplex virus type 1 attachment and infection by sulfated polyglycerols with different architectures (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Pouyan, Paria

Nie, Chuanxiong

Bhatia, Sumati

Wedepohl, Stefanie

Achazi, Katharina

Osterrieder, Nikolaus (WE 5)

Haag, Rainer

Quelle

Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences / publ. by the American Chemical Society

Bandzählung: 22

Heftzählung: 4

Seiten: 1545 – 1554

ISSN: 1525-7797

Sprache

Englisch

Verweise

URL (Volltext): https://pubs.acs.org/doi/10.1021/acs.biomac.0c01789

DOI: 10.1021/acs.biomac.0c01789

Pubmed: 33706509

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Inhibition of herpes simplex virus type 1 (HSV-1) binding to the host cell surface by highly sulfated architectures is among the promising strategies to prevent virus entry and infection. However, the structural flexibility of multivalent inhibitors plays a major role in effective blockage and inhibition of virus receptors. In this study, we demonstrate the inhibitory effect of a polymer scaffold on the HSV-1 infection by using highly sulfated polyglycerols with different architectures (linear, dendronized, and hyperbranched). IC50 values for all synthesized sulfated polyglycerols and the natural sulfated polymer heparin were determined using plaque reduction infection assays. Interestingly, an increase in the IC50 value from 0.03 to 374 nM from highly flexible linear polyglycerol sulfate (LPGS) to less flexible scaffolds, namely, dendronized polyglycerol sulfate and hyperbranched polyglycerol sulfate was observed. The most potent LPGS inhibits HSV-1 infection 295 times more efficiently than heparin, and we show that LPGS has a much reduced anticoagulant capacity when compared to heparin as evidenced by measuring the activated partial thromboplastin time. Furthermore, prevention of infection by LPGS and the commercially available drug acyclovir were compared. All tested sulfated polymers do not show any cytotoxicity at concentrations of up to 1 mg/mL in different cell lines. We conclude from our results that more flexible polyglycerol sulfates are superior to less flexible sulfated polymers with respect to inhibition of HSV-1 infection and may constitute an alternative to the current antiviral treatments of this ubiquitous pathogen.