Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral Cat fu: Broad spectrum polymeric antivirals Aleksandra Synowiec a,b , Irma Gryniuk c , Magdalena Pachota a,b , Łukasz Strzelec b ,OlgaRoman d , Katarzyna Kłysik-Trzciańska e , Mateusz Zając e ,IngaDrebot a , Katarzyna Gula a , Aleksandra Andruchowicz f , Zenon Rajfur g , Krzysztof Szczubiałka e , Maria Nowakowska e,** , Krzysztof Pyrc a,* a Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387, Krakow, Poland b Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Krakow, Poland c Department of Cell Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Krakow, Poland d Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Krakow, Poland e Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387, Krakow, Poland f Veterinary Practice AMBUVET, Pod Fortem 2E, 31-302, Krakow, Poland g Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Sciences, Jagiellonian University, Lojasiewicza 11, 30-348, Krakow, Poland ARTICLEINFO Keywords: Synthetic polymers poly(sodium 4-styrenesulfonates) PSSNa Antivirals Feline herpesvirus type 1 FHV-1 Feline calicivirus FCV Catfu ABSTRACT Feline herpesvirus type 1 (FHV-1) and feline calicivirus (FCV) are considered as main causes of feline upper respiratory tract disease and the most common clinical manifestations include rhinotracheitis, conjunctivitis, andnasal/facialulcerations.Whiletheprimaryinfectionisrelativelymild,secondaryinfectionsposeathreatto young or immunocompromised cats and may result in a fatal outcome. In this study, we made an efort to evaluateantiviralpotencyofpoly(sodium4-styrenesulfonates)(PSSNa)aspotentFHV-1andFCVinhibitorsfor topicaluse.MechanisticstudiesshowedthatPSSNaexhibitsadiferentmechanismofactiondependingontarget species. While PSSNa acts directly on FHV-1 particles blocking their interaction with the host's cell and pre- venting the infection, the antiviral potency against FCV is based on inhibition at late stages of the viral re- plication cycle. Altogether, PSSNa polymers are promising drug candidates to be used in the treatment and prevention of the viral upper respiratory tract disease (URTD), regardless of the cause. 1. Introduction Feline upper respiratory tract disease (URTD), colloquially termed as ‘cat fu’, is a relatively mild condition, manifested by oral or nasal discharges, lethargy, pyrexia, conjunctivitis and sneezing (Helpsetal., 2005; Binns et al., 2000). The disease, however, may progress to the severe sequelae, with potentially fatal outcome (Bannasch and Foley, 2005). Feline herpesvirus type 1 (FHV-1) and feline calicivirus (FCV) areconsideredtobethetwomajorcausesofURTDs(Helpsetal.,2005; Bannasch and Foley, 2005; Fernandez et al., 2017; Cohn, 2011). Caliciviridae family encompasses non-enveloped, single-stranded, positive-senseRNAviruses(FieldsBNetal.,2013)thatcaninfectboth humans and animals (Ohlinger et al., 1993; Bank-Wolf et al., 2010; Hurleyetal.,2004).Felinecalicivirus(FCV)(Vesivirus (FieldsBNetal., 2013))isprevalentworldwideinthedomesticcatpopulation(Radford et al., 2009), and is commonly associated with oral ulceration, salivation,chronicstomatitis,mildrespiratoryorconjunctivaldisorders and limping syndrome (Dawson et al., 1994; Reubel et al., 1992; TerWee et al., 1997). It has been, however, noted that some FCV iso- lates cause outbreaks with mortality rates reaching 40–60% (Hurley etal.,2004; Coyneetal.,2006; Pedersen et al., 2000; Reynolds et al., 2009; Schulzetal.,2011).Noadequateantiviraltreatmentisavailable. Previous reports show that FCV infection may be inhibited in vitro (McDonaghetal.,2015; Wuetal.,2015; Fumianetal.,2018),butthese fndings were not confrmed in clinic. Herpesviridae family encompasses enveloped, double-stranded DNA viruses associated with incurable, lifelong lasting herpetic infections. Felineherpesvirustype1(FHV-1,felidherpesvirus1)isclassifedunder the genus Varicellovirus and within the Alphaherpesvirinae subfamily (Davison et al., 2009). The virus is present in the domestic cat popu- lationworldwide,causingviralrhinotracheitis(FVR)andoculardisease (Gould, 2011; Hartley, 2010; Bistner et al., 1971; Stiles, 2003). It is https://doi.org/10.1016/j.antiviral.2019.104563 Received15February2019;Receivedinrevisedform15July2019;Accepted17July2019 * Corresponding author. ** Corresponding author. E-mail addresses: nowakows@chemia.uj.edu.pl (M. Nowakowska), k.a.pyrc@uj.edu.pl (K. Pyrc). URL: http://virogenetics.info (K. Pyrc). Antiviral Research 170 (2019) 104563 Available online 17 July 2019 0166-3542/ © 2019 Elsevier B.V. All rights reserved. T