Antiviral Research 88 (2010) 343346 Contents lists available at ScienceDirect Antiviral Research journal homepage: Short communication Antiseptic properties of two calix4arenes derivatives on the human coronavirus 229E? C. Geller, S. Fontanay, M. Mourer, H. Massimba Dibama, J.-B. Regnouf-de-Vains, C. Finance, R.E. Duval GEVSM, SRSMC, UMR 7565, Nancy-University, CNRS, Faculty of Pharmacy, 5 rue Albert Lebrun, BP 80403, 54001 Nancy Cedex, France a r t i c l ei n f o Article history: Received 25 June 2010 Received in revised form 1 September 2010 Accepted 14 September 2010 Keywords: HCoV 229E tetra-para-Sulfonato-calix4arene 1,3-Bis(bithiazolyl)-tetra-para-sulfonato- calix4arene Antiseptic Virucidal a b s t r a c t Facing the lack in specifi c antiviral treatment, it is necessary to develop new means of preven- tion. In the case of the Coronaviridae this family is now recognized as including potent human pathogens causing upper and lower respiratory tract infections as well as nosocomial ones. Within the purpose of developing new antiseptics molecules, the antiseptic virucidal activity of two calix4arene derivatives, the tetra-para-sulfonato-calix4arene (C4S) and the 1,3-bis(bithiazolyl)- tetra-para-sulfonato-calix4arene (C4S-BTZ) were evaluated toward the human coronavirus 229E (HCoV 229E). Comparing these results with some obtained previously with chlorhexidine and hexami- dine, (i) these two calixarenes did not show any cytotoxicity contrary to chlorhexidine and hexamidine, (ii) C4S showed as did hexamidine, a very weak activity against HCoV 229E, and (iii) the C4S-BTZ showed a stronger activity than chlorhexidine, i.e. 2.7 and 1.4log10reduction in viral titer after 5min of contact with 103molL1solutions of C4S-BTZ and chlorhexidine, respectively. Thus, the C4S-BTZ appeared as a promising virucidal (antiseptic) molecule. 2010 Elsevier B.V. All rights reserved. Thelackinspecifi cantiviraltreatmentsisstillpersisting,consid- ering the large variety of viruses already circulating among human population and the potential emerging ones. The Coronaviridae family illustrates this problem. Indeed, no specifi c treatment is available to fi ght coronaviruses infections, while they are known to be responsible for upper and lower tract infections as well as nosocomialones.Thus,effi cientmeansofprevention,asanadapted antisepsis-disinfection(ATS-D),shouldbedevelopedtopreventthe environmental spread of such infections. Human coronaviruses (HCoV) were historically known to be responsible for about 20% of common colds and other upper respi- ratory tract infections (Larson et al., 1980). Before the SARS (severe acute respiratory syndrome) epidemic in 20022003, only two Abbreviations:ATS-D,antiseptic-disinfectantorantisepsis-disinfection; C4S,tetra-para-sulfonato-calix4arene;C4S-BTZ,1,3-bis(bithiazolyl)-tetra- para-sulfonato-calix4arene; CC50, cytotoxic concentration 50%; CHX, chlorhexi- dine; HCoV, human coronavirus; HXM, hexamidine; IC50, inhibitory concentration 50%; MTT, methyl thiazole tetrazolium; NR, neutral red; SARS, severe acute respi- ratory syndrome. ?This work was presented in part at the 4th European Congress of Virology, #805, Cernobbio, Como Lake, Italy, 711 April 2010. Corresponding author at: Groupe dEtude des Vecteurs Supramolculaires du Mdicament(GEVSM),StructureetRactivitdesSystmesMolculairesComplexes (SRSMC), Nancy-University, CNRS, Faculty of Pharmacy, 5 rue Albert Lebrun, BP 80403, 54001 Nancy Cedex, France. Tel.: +33 (0) 3 83 68 23 36; fax: +33 (0) 3 83 68 23 57. E-mail address: raphael.duvalpharma.uhp-nancy.fr (R.E. Duval). HCoVwereknown,the229EstrainandtheOC43strain.Thisserious outbreak, due to a newly discovered HCoV, the SARS-CoV (Ksiazek et al., 2003; Peiris et al., 2003), reinforced the interest into the Coronaviridae family. Indeed, coronaviruses were since involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates (Gagneur et al., 2002; Gerna et al., 2006), elderly people (Falsey et al., 2002) and immunosuppressed patients (Gerna et al., 2007; Pene et al., 2003). Furthermore, they have been shown to survive for at least several hours under different environmental conditions (Ijaz et al., 1985; Lai et al., 2005; Rabenau et al., 2005a; Sizun et al., 2000). Finally, their adaptive properties and their ability of species bar- rier crossing, involve a signifi cant possibility of new coronaviruses emergence (Laude et al., 1998; Li et al., 2005; Vijgen et al., 2005). Thus, these specifi cities (i.e. pathogenicity, potential environmen- tal resistance and evolutionary ability) make the Coronaviridae family a pertinent model for studying ATS-D activity. New antiviral molecules are urgently needed. Within this pur- pose, some macrocyclic compounds belonging to the calixarene family (de Ftima et al., 2009; Rodik et al., 2009), have already been shown to be interesting as anti-HIV and anti-HSV agents (Coveney and Costello, 2005;