1. Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV‑2 Inhibition
- Author
-
Ai, Xiangzhao, Wang, Dan, Honko, Anna, Duan, Yaou, Gavrish, Igor, Fang, Ronnie H, Griffiths, Anthony, Gao, Weiwei, and Zhang, Liangfang
- Subjects
Prevention ,Lung ,Vaccine Related ,Bioengineering ,Nanotechnology ,Biodefense ,Infectious Diseases ,Pneumonia & Influenza ,Emerging Infectious Diseases ,Pneumonia ,Infection ,COVID-19 ,Heparin ,Humans ,Nanostructures ,Polysaccharides ,SARS-CoV-2 ,COVID-19 Drug Treatment ,Chemical Sciences ,General Chemistry - Abstract
Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles ("cellular nanosponges") mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that increasing surface heparin density on the cellular nanosponges can promote their inhibition against SARS-CoV-2. Specifically, cellular nanosponges are made with azido-expressing host cell membranes followed by conjugating heparin to the nanosponge surfaces. Cellular nanosponges with a higher heparin density have a larger binding capacity with viral S proteins and a significantly higher inhibition efficacy against SARS-CoV-2 infectivity. Overall, surface glycan engineering of host-mimicking cellular nanosponges is a facile method to enhance SARS-CoV-2 inhibition. This approach can be readily generalized to promote the inhibition of other glycan-dependent viruses.
- Published
- 2021