The Influence of the AgNPs Ligand on the Antiviral Activity Against HSV-2

Emilia Tomaszewska,1 Katarzyna Bednarczyk,1 Martyna Janicka,2,3 Marcin Chodkowski,2 Malgorzata Krzyzowska,2 Grzegorz Celichowski,1 Jarosław Grobelny,1 Katarzyna Ranoszek-Soliwoda1 1University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Lodz, 90-236, Poland; 2Military Institute of Hygiene and Epidemiology, Laboratory of Nanobiology and Biomaterials, Warsaw, 01-063, Poland; 3Division of Microbiology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, 02-786, PolandCorrespondence: Katarzyna Ranoszek-Soliwoda, University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Pomorska, 163, Lodz, 90-236, Poland, Tel +48 42 6354663, Fax +48 42 6355832, Email [email protected]: In this paper, we discuss the influence of the ligand type present on the surface of silver nanoparticles (AgNPs) on its affinity to the virus surface and its virucidal activity against herpes simplex virus type 2 (HSV-2). We selected four different ligands, which potentially exhibit different affinity to the HSV-2 virus surface and used them for functionalization of AgNPs: i) sodium citrate: ii) tannic acid; iii) 1-mercaptoundecane-1-sulfonate (MUS); iv) and poly(ethylene glycol) (PEG).Methods: The antiviral activity was performed by in vitro Vero cell culture. Anti- inflammatory activity was performed by measurement of NF-κB activity. The antiviral potential of functional NPs in vivo was tested with HSV-2 model of genital infection. Cryo- transmission electron microscopy (cryo-TEM) was used to directly visualize the interactions or lack of interactions of functional NPs with the surface of the HSV-2 virus and to assess their affinity for the virus surface.Results: It was found that the surface chemistry of NPs plays a key role in modulation of its interaction with the HSV-2 virus. Two of the selected ligands (sodium citrate and PEG) were inert and show no affinity to the virus surface. AgNPs functionalized with heparan sulfate-mimic ligand (MUS) showed high affinity to the virus surface, and the appearance of these interactions resulted in virus deactivation in about 50%. In the case of silver nanoparticles functionalized with tannic acid, the assessment of the affinity is difficult to be resolved, mainly because TA-AgNPs exhibit very strong virucidal effect (~100%) and immediately after the contact of the HSV-2 virus with those NPs the virus structure is being destroyed.Discussion: The obtained results indicate that the high affinity of functional nanoparticles to the virus surface does not provide the high virucidal effectiveness. The most effective revealed to be TA-AgNPs which exhibit very strong virucidal effect against HSV-2 virus. Keywords: antiviral functional nanoparticles, interactions of nanoparticles with HSV-2, cryo-TEM, surface chemistry of antiviral nanoparticles