Potent virustatic polymer-lipid nanomimics block viral entry and inhibit malaria parasites in vivo
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2022-09-28
Date Acceptance
2022-04-08
Citation
ACS Central Science, 2022, 8 (9), pp.1238-1257
ISSN
2374-7943
Publisher
American Chemical Society
Start Page
1238
End Page
1257
Journal / Book Title
ACS Central Science
Volume
8
Issue
9
Copyright Statement
© 2022 The Authors. Published by American Chemical Society. This article is available open access under a Creative Commons Attribution License 4.0 International (https://creativecommons.org/licenses/by/4.0/)
License URL
Sponsor
Wellcome Trust
Engineering and Physical Sciences Research Council
Commission of the European Communities
Commission of the European Communities
Commission of the European Communities
Commission of the European Communities
Wellcome Trust
Wellcome Trust
Grant Number
209121/Z/17/Z
EP/S023259/1
839137
893158
ERC-2013-CoG-616417
862204
100993/Z/13/Z
100993/Z/13/Z
Subjects
Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
PLASMODIUM-FALCIPARUM MEROZOITES
ERYTHROCYTE INVASION
SULFATED GLYCOSAMINOGLYCANS
CORRELATION SPECTROSCOPY
MICRO-ASSAY
HEPARIN
NANOPARTICLES
MOLECULES
PLATFORM
03 Chemical Sciences
Publication Status
Published
Date Publish Online
2022-05-03