The coronavirus SARS-CoV-2 causes the current global outbreak of COVID-19. The virus has glycoprotein spikes on its surface. These spikes help SARS-CoV-2 enter host cells by binding to receptors on the surface of the host cells’ membrane, such as the angiotensin-converting enzyme 2 (ACE2). Blocking these interactions could keep the virus from infecting cells. Drugs that bind to the spike protein are, thus, one approach for COVID-19 treatment and prevention. Offering the virus an entirely different target could be another promising approach to protect cells from the virus.
Anthony Griffiths, Boston University School of Medicine, MA, USA, Liangfang Zhang, University of California San Diego, La Jolla, USA, and colleagues have developed nanoparticle decoys that display the virus’ natural targets, including ACE2, on their surface. These decoys could prevent SARS-CoV-2 from entering cells by binding to it and blocking its spike proteins from further interactions. To create the nanosponges, the researchers coated a nanoparticle polymer core made from poly(lactic-co-glycolic acid) (PLGA) with cell membranes from either human lung epithelial cells or macrophages, two cell types that can be infected by SARS-CoV-2.
The team showed that the resulting nanosponges contained ACE2 and other viral receptors using Western blot analysis. When administered to mice, the nanosponges did not show any short-term toxicity. The researchers treated cells simultaneously with SARS-CoV-2 and the lung-epithelial or macrophage nanosponges in vitro. Both decoys neutralized SARS-CoV-2 and prevented it from infecting cells to a similar extent. In theory, this nanosponge approach would work even if SARS-CoV-2 mutates to resist other therapies, as long as the virus targets the same types of receptors. According to the researchers, it could also be used against other viruses.
- Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity,
Qiangzhe Zhang, Anna Honko, Jiarong Zhou, Hua Gong, Sierra N. Downs, Jhonatan Henao Vasquez, Ronnie H. Fang, Weiwei Gao, Anthony Griffiths, Liangfang Zhang,
Nano Lett. 2020.
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