Potent Virustatic Polymer–Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo
mediaposted on 2022-05-03, 20:11 authored by Adrian Najer, Joshua Blight, Catherine B. Ducker, Matteo Gasbarri, Jonathan C. Brown, Junyi Che, Håkon Høgset, Catherine Saunders, Miina Ojansivu, Zixuan Lu, Yiyang Lin, Jonathan Yeow, Omar Rifaie-Graham, Michael Potter, Renée Tonkin, Jelle Penders, James J. Doutch, Athina Georgiadou, Hanna M. G. Barriga, Margaret N. Holme, Aubrey J. Cunnington, Laurence Bugeon, Margaret J. Dallman, Wendy S. Barclay, Francesco Stellacci, Jake Baum, Molly M. Stevens
Infectious 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 nanoparticles that mimic functional components of host cell membranes, yielding multivalent nanomimics 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 coronavirus 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.
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requiring innovative broadobserved virustatic modemimic functional componentsmalaria parasite bloodinhibit malaria parasiteshost cell membranesred blood cellsyielding multivalent nanomimicsepithelial cellswherein nanomimicvivo vitro varied pathogenstreatment alternativessubstantial burdenstage merozoitesspectrum prophylacticsecondarily targetedpolymer nanomimicsnanomimics formingmerozoite invasioninvasive capacityinhibited pathogensimmune recognitionhigher dosesglobal populationsfemtomolar concentrationsefficient inhibitiondirectly bindingalso testedadaptable platform