Broad-spectrumnon-toxicantiviralnanoparticleswithavirucidalinhibitionmechanismValeriaCagno,PatriziaAndreozzi,MarcoD’Alicarnasso,PauloJacobSilva,MarieMueller,MarieGalloux,RonanLeGoffic,SamuelT.Jones,MartaVallino,JanHodek,JanWeber,SoumyoSen,Emma-RoseJaneček,AhmetBekdemir,BarbaraSanavio,ChiaraMartinelli,ManuelaDonalisio,Marie-AnneRameixWelti,Jean-FrancoisEleouet,YanxiaoHan,LaurentKaiser,LelaVukovic,CarolineTapparel,PetrKrál,SilkeKrol,DavidLembo&FrancescoStellacci
NatureMaterialsvolume17,pages195–203(2018)
DipartimentodiScienzeClinicheeBiologiche,UniverisitàdegliStudidiTorino,Orbassano,Italy- ValeriaCagno,DavidLembo
InstituteofMaterials,EcolePolytechniqueFédéraledeLausanne(EPFL),Lausanne,Switzerland- ValeriaCagno,MarieMueller
SITorino
SSTorino
SSSestoFiorentino
SSPortici
SSBari
Broad-spectrumnon-toxicantiviralnanoparticleswithavirucidalinhibitionmechanismValeriaCagno,PatriziaAndreozzi,MarcoD’Alicarnasso,PauloJacobSilva,MarieMueller,MarieGalloux,RonanLeGoffic,SamuelT.Jones,MartaVallino,JanHodek,JanWeber,SoumyoSen,Emma-RoseJaneček,AhmetBekdemir,BarbaraSanavio,ChiaraMartinelli,ManuelaDonalisio,Marie-AnneRameixWelti,Jean-FrancoisEleouet,YanxiaoHan,LaurentKaiser,LelaVukovic,CarolineTapparel,PetrKrál,SilkeKrol,DavidLembo&FrancescoStellacci
NatureMaterialsvolume17,pages195–203(2018)
DipartimentodiScienzeClinicheeBiologiche,UniverisitàdegliStudidiTorino,Orbassano,Italy- ValeriaCagno,DavidLembo
InstituteofMaterials,EcolePolytechniqueFédéraledeLausanne(EPFL),Lausanne,Switzerland- ValeriaCagno,MarieMueller
Sviluppodinanoparticelleconazionevirucidaadampiospettro
Infezionivirali
Prevenzione:vaccini
Dopol’infezione:farmaciantivirali numerolimitatovirus-specificiazioneintracellulare(replicazionevirale)tossicitàintrinseca
Sostanzevirustatiche azioneextracellulareampiospettronontossiche
Legametraviruserecettorecellulare(comuneapiùvirus)
VAL(viralattachmentligand)<===>HSPG(HeparansulfateProteoglycans)Multiplebasicaminoacid caricanegativadelgrupposolfato
legamereversibile=>inutilicomefarmaci
Virustatico
Shortlinker
MercaptoetilsulfonatoMES
Virucida???
Longlinker
MercaptoundecanosulfonatoMUS
GliattualivirustaticimimanolastrutturadiHSPGShortlinkers=>legameapocheunitàripetutedelVAL=>legamedeboleereversibile
Farmacoideale: virucida=>inattivazioneirreversibileampiospettroNontossico
10
b,Heparin,MES-NPsandMUS:OT-NPsviralinfectivitycurvesandvirucidalassays.Thepercentagesofinfectionwerecalculatedbycomparingthenumberofplaquesintreatedanduntreatedwells.c,VirucidalactivityofMUS-coatedNPsagainstHPV-16,RSV,LV-VSV-G(indicatedasLV)andDENV-2viruses.d,MUS:OT-NPsinhibitionofviralinfectivityagainstHSV-2versustime(minutes).
InfectivityupondilutionCelltoxicity
Infectivity
a–c,SamplesimagedusingdrynegativelystainedTEM(a)orunstainedcryo-TEM(b,c).Thescalebarsare100 nm.
HSV-2herpessimplexvirus2
d,PercentageanddistributionofNPs(MESorMUS:OT)associatedwithHSV-2immediatelyandafter90 min
SupplementaryFigure11:VirucidalAssaysandInteractionwithHSV-2virusesforEG2-OH-NPs.A)Cryo-TEM(up)andnegativestainingTEM(down)imagesofHSV-2virus(105pfu)treatedwithEG2-OH-NPs.B)VirucidalassayofHSV-2virustreatedwithEG2-OH-NPs.n=3C)%distributionofnotsulfonatedEG2-OHNPsassociatedwithHSV-2after1.5hofincubation.ThemajorityofviruseswerenotassociatedwithanyNP.Thedistributionwascalculatedanalysingbetween50and100images.Thescalebarsindicate100nm
SupplementaryFigure22:Cryo-TEMandTEMofHSV-2withenvelope.A)Cryo-TEMandB)negativestainingTEMimagesofHSV-2virus(105pfu)treatedwithNPs.(Scalebar100nm)
SupplementaryFigure12:MUS:OT-NPsassociatedwithHPV-16PsVs.Intheupperpaneltheimageswereacquiredbycryo-TEM.Inthepanelbelowthesampleswerestainedwithuranylacetate0.5%for5minandacquiredbyTEM.ImagesaanddrepresenttheHPV-16,whileb,c,eandfrepresentdifferenttypesofNPsassociationwithHPV-16PsVs.Thescalebarsindicate100nm.
HPVhumanpapillomavirus
a,CartoonofthevirucidalactivityofMUS:OT-NPscomparedtoMES-NPs.
RSVrespiratorysyncytialvirus
humancervicovaginalhistocultures EpiVaginaltissues
PhilipsCM10
