TY - JOUR A1 - Sivarajan, Rinu A1 - Oberwinkler, Heike A1 - Roll, Valeria A1 - König, Eva-Maria A1 - Steinke, Maria A1 - Bodem, Jochen T1 - A defined anthocyanin mixture sourced from bilberry and black currant inhibits Measles virus and various herpesviruses JF - BMC Complementary Medicine and Therapies N2 - Background Anthocyanin-containing plant extracts and carotenoids, such as astaxanthin, have been well-known for their antiviral and anti-inflammatory activity, respectively. We hypothesised that a mixture of Ribes nigrum L. (Grossulariaceae) (common name black currant (BC)) and Vaccinium myrtillus L. (Ericaceae) (common name bilberry (BL)) extracts (BC/BL) with standardised anthocyanin content as well as single plant extracts interfered with the replication of Measles virus and Herpesviruses in vitro. Methods We treated cell cultures with BC/BL or defined single plant extracts, purified anthocyanins and astaxanthin in different concentrations and subsequently infected the cultures with the Measles virus (wild-type or vaccine strain Edmonston), Herpesvirus 1 or 8, or murine Cytomegalovirus. Then, we analysed the number of infected cells and viral infectivity and compared the data to non-treated controls. Results The BC/BL extract inhibited wild-type Measles virus replication, syncytia formation and cell-to-cell spread. This suppression was dependent on the wild-type virus-receptor-interaction since the Measles vaccine strain was unaffected by BC/BL treatment. Furthermore, the evidence was provided that the delphinidin-3-rutinoside chloride, a component of BC/BL, and purified astaxanthin, were effective anti-Measles virus compounds. Human Herpesvirus 1 and murine Cytomegalovirus replication was inhibited by BC/BL, single bilberry or black currant extracts, and the BC/BL component delphinidin-3-glucoside chloride. Additionally, we observed that BC/BL seemed to act synergistically with aciclovir. Moreover, BC/BL, the single bilberry and black currant extracts, and the BC/BL components delphinidin-3-glucoside chloride, cyanidin-3-glucoside, delphinidin-3-rutinoside chloride, and petunidin-3-galactoside inhibited human Herpesvirus 8 replication. Conclusions Our data indicate that Measles viruses and Herpesviruses are differentially susceptible to a specific BC/BL mixture, single plant extracts, purified anthocyanins and astaxanthin. These compounds might be used in the prevention of viral diseases and in addition to direct-acting antivirals, such as aciclovir. KW - anthocyanin KW - astaxanthin KW - bilberry KW - black currant KW - herpesvirus KW - measels virus Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301423 VL - 22 ER - TY - JOUR A1 - Geiger, Nina A1 - König, Eva-Maria A1 - Oberwinkler, Heike A1 - Roll, Valeria A1 - Diesendorf, Viktoria A1 - Fähr, Sofie A1 - Obernolte, Helena A1 - Sewald, Katherina A1 - Wronski, Sabine A1 - Steinke, Maria A1 - Bodem, Jochen T1 - Acetylsalicylic acid and salicylic acid inhibit SARS-CoV-2 replication in precision-cut lung slices JF - Vaccines N2 - Aspirin, with its active compound acetylsalicylic acid (ASA), shows antiviral activity against rhino- and influenza viruses at high concentrations. We sought to investigate whether ASA and its metabolite salicylic acid (SA) inhibit SARS-CoV-2 since it might use similar pathways to influenza viruses. The compound-treated cells were infected with SARS-CoV-2. Viral replication was analysed by RTqPCR. The compounds suppressed SARS-CoV-2 replication in cell culture cells and a patient-near replication system using human precision-cut lung slices by two orders of magnitude. While the compounds did not interfere with viral entry, it led to lower viral RNA expression after 24 h, indicating that post-entry pathways were inhibited by the compounds. KW - acetylsalicylic acid KW - salicylic acid KW - antiviral activity KW - aspirin KW - SARS-CoV-2 KW - precision-cut lung slices Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-289885 SN - 2076-393X VL - 10 IS - 10 ER - TY - JOUR A1 - Siverino, Claudia A1 - Fahmy-Garcia, Shorouk A1 - Mumcuoglu, Didem A1 - Oberwinkler, Heike A1 - Muehlemann, Markus A1 - Mueller, Thomas A1 - Farrell, Eric A1 - van Osch, Gerjo J. V. M. A1 - Nickel, Joachim T1 - Site-directed immobilization of an engineered bone morphogenetic protein 2 (BMP2) variant to collagen-based microspheres induces bone formation in vivo JF - International Journal of Molecular Sciences N2 - For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs. KW - bone morphogenetic protein 2 (BMP2) KW - bone regeneration KW - covalent coupling KW - subcutaneous animal model Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284572 SN - 1422-0067 VL - 23 IS - 7 ER -