Abstract
The ability of pathogens to develop drug resistance is a global health challenge. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an urgent need wherein several variants of concern resist neutralization by monoclonal antibody (mAb) therapies and vaccine-induced sera. Decoy nanoparticles—cell-mimicking particles that bind and inhibit virions—are an emerging class of therapeutics that may overcome such drug resistance challenges. To date, quantitative understanding as to how design features impact performance of these therapeutics is lacking. To address this gap, this study presents a systematic, comparative evaluation of various biologically derived nanoscale vesicles, which may be particularly well suited to sustained or repeated administration in the clinic due to low toxicity, and investigates their potential to inhibit multiple classes of model SARS-CoV-2 virions. A key finding is that such particles exhibit potent antiviral efficacy across multiple manufacturing methods, vesicle subclasses, and virus-decoy binding affinities. In addition, these cell-mimicking vesicles effectively inhibit model SARS-CoV-2 variants that evade mAbs and recombinant protein-based decoy inhibitors. This study provides a foundation of knowledge that may guide the design of decoy nanoparticle inhibitors for SARS-CoV-2 and other viral infections.
| Original language | English (US) |
|---|---|
| Article number | 2200125 |
| Journal | Small |
| Volume | 18 |
| Issue number | 19 |
| DOIs | |
| State | Published - May 12 2022 |
Funding
This work was supported in part by the National Science Foundation under Grant No. 1844219 (N.P.K., J.N.L.) and 1844336 (N.P.K.) and a gift from Kairos Ventures (J.N.L.). This work was supported by the Northwestern University – Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553). This work made use of the BioCryo facility of Northwestern University's NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS‐2025633), the IIN, and Northwestern's MRSEC program (NSF DMR‐1720139). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. (T.F.G. # DGE‐1842165 and D.M.S. # DGE‐1324585). T.F.G. and R.E.M. were supported in part by the Northwestern University Graduate School Cluster in Biotechnology, Systems, and Synthetic Biology, which is affiliated with the Biotechnology Training Program. R.E.M. was supported in part by the National Institutes of Health Training Grant (T32GM008449) through Northwestern University's Biotechnology Training Program. Biological and chemical analysis was performed in the Analytical bioNanoTechnology Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS‐1542205). This work was supported by the Northwestern University Sanger Sequencing Facility. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors(s) and do not necessarily reflect the views of the National Science Foundation. The authors kindly thank the Kamat and Leonard lab members for useful discussions throughout the planning, experimental, analysis, and writing phases of this project. This work was supported in part by the National Science Foundation under Grant No. 1844219 (N.P.K., J.N.L.) and 1844336 (N.P.K.) and a gift from Kairos Ventures (J.N.L.). This work was supported by the Northwestern University – Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553). This work made use of the BioCryo facility of Northwestern University's NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern's MRSEC program (NSF DMR-1720139). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. (T.F.G. # DGE-1842165 and D.M.S. # DGE-1324585). T.F.G. and R.E.M. were supported in part by the Northwestern University Graduate School Cluster in Biotechnology, Systems, and Synthetic Biology, which is affiliated with the Biotechnology Training Program. R.E.M. was supported in part by the National Institutes of Health Training Grant (T32GM008449) through Northwestern University's Biotechnology Training Program. Biological and chemical analysis was performed in the Analytical bioNanoTechnology Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). This work was supported by the Northwestern University Sanger Sequencing Facility. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors(s) and do not necessarily reflect the views of the National Science Foundation. The authors kindly thank the Kamat and Leonard lab members for useful discussions throughout the planning, experimental, analysis, and writing phases of this project.
Keywords
- ACE2
- SARS-CoV-2
- decoys
- extracellular vesicles
- nanovesicles
ASJC Scopus subject areas
- General Chemistry
- Engineering (miscellaneous)
- Biotechnology
- General Materials Science
- Biomaterials
