Nanosponges intercept coronavirus infection

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Science Translational Medicine  01 Jul 2020:
Vol. 12, Issue 550, eabd3078
DOI: 10.1126/scitranslmed.abd3078


Nanoparticles cloaked in human lung and immune cell membranes act as decoys to neutralize SARS-CoV-2 in cell culture, preventing host cell infection.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe global public health crisis. The search for new drugs or vaccines is often hampered by a limited understanding of underlying molecular mechanisms in new emerging viruses such as SARS-CoV-2. Detailed understanding of pathophysiological mechanisms is often required to identify potential drug targets. Another limitation of existing antiviral therapy is specificity toward viral species, which may be rendered ineffective once the virus accumulates additional mutations.

In a recent paper, Zhang et al. developed a biomimetic decoy approach whereby the virus is tricked into latching onto nanoparticles instead of the host lung cells. Nanosponges consisting of a biodegradable polymeric core of U.S. Food and Drug Administration–approved poly(lactic-co-glycolic) were coated with human cell–derived membranes from lung epithelial or immune cells that express critical receptors (e.g., angiotensin-converting enzymes 2) that the virus uses for cellular entry. In vitro, these nanosponges reduced the infectivity of live SARS-CoV-2 in a dose-dependent manner. At 5 mg/ml the lung- and macrophage membrane–cloaked sponges inhibited up to 93% and 88% of SARS-CoV-2 infectivity, respectively. Cloaking nanosponges with the cell membranes of macrophages conferred the additional benefit of soaking up circulating inflammatory cytokine proteins implicated in the immune response to the infection.

To assess short-term biocompatibility, the nanosponges were delivered intratracheally into the lungs of wild-type mice. Histopathology of the lung tissues and analysis of blood for immune markers three days after administration indicated short-term safety. However, further studies need to be conducted to evaluate the nanosponges’ efficacy in animal disease models, as well as long-term biocompatibility. In addition, several concerns need to be addressed before clinical trials, such as identifying the most efficient way to deliver the nanosponages (e.g., directly into the lungs of intubated patients, through an inhaler, or even intravenously to treat the complications of a cytokine storm).

These membrane-cloaked nanoparticles are a promising addition to the armamentarium of vaccines and therapies against SARS-CoV-2. Their usefulness should remain, provided the host receptor required for virus cell invasion does not change. These nanosponges hold potential for broad-spectrum antiviral therapy, which remains to be further explored.

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