Najer, AdrianBlight, JoshuaDucker, Catherine B.Gasbarri, MatteoBrown, Jonathan C.Che, JunyiHogset, HakonSaunders, CatherineOjansivu, MiinaLu, ZixuanLin, YiyangYeow, JonathanRifaie-Graham, OmarPotter, MichaelTonkin, ReneePenders, JelleDoutch, James J.Georgiadou, AthinaBarriga, Hanna M. G.Holme, Margaret N.Cunnington, Aubrey J.Bugeon, LaurenceDallman, Margaret J.Barclay, Wendy S.Stellacci, FrancescoBaum, JakeStevens, Molly M.2022-07-182022-07-182022-07-182022-05-0310.1021/acscentsci.1c01368https://infoscience.epfl.ch/handle/20.500.14299/189386WOS:000821274300001Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanopartides that mimic functional components of host cell membranes, yielding multivalent nano-mimics that act by directly binding to varied pathogens. Nanomimic blood circulation time was prolonged by reformulating polymer-lipid hybrids. Femtomolar concentrations of the polymer nanomimics were sufficient to inhibit herpes simplex virus type 2 (HSV-2) entry into epithelial cells, while higher doses were needed against severe acute respiratory syndrome comnavirus 2 (SARS-CoV-2). Given their observed virustatic mode of action, the nanomimics were also tested with malaria parasite blood-stage merozoites, which lose their invasive capacity after a few minutes. Efficient inhibition of merozoite invasion of red blood cells was demonstrated both in vitro and in vivo using a preclinical rodent malaria model. We envision these nanomimics forming an adaptable platform for developing pathogen entry inhibitors and as immunomodulators, wherein nanomimic-inhibited pathogens can be secondarily targeted to sites of immune recognition.Chemistry, MultidisciplinaryChemistryplasmodium-falciparum merozoiteserythrocyte invasionsulfated glycosaminoglycanscorrelation spectroscopymicro-assayheparinnanoparticlesmoleculesplatformtext::journal::journal article::research article