Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition

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.

An engineered nano-liposome-human ACE2 decoy neutralizes SARS-CoV-2 Spike protein-induced inflammation in both murine and human macrophages

“…The severity of COVID-19 is associated with the SARS-CoV-2 load, and the activation of host inflammatory responses. For this reason, mitigating the inflammatory response is critical to develop anti-SARS-CoV-2 therapies 63 . NF-κB signaling has been implicated as a key pathway underlying COVID-19-associated inflammation 15 , and we recently revealed the important role of IKKβ, a central inflammatory coordinator through activating NF-κB, in the regulation of other viral protein (e.g.…”

COVID-19 inflammation and implications in drug delivery

“…Interestingly, the designed system attaching both the virus and cytokines exhibited better antiviral capacity than the nanovesicles obtained from 293T/ACE2 alone [ 92 ]. Recently, THP-1 membrane-derived PLGA NPs of approximatively 100 nm were also evaluated for their SARS-CoV-2 inhibition, but the main focus was the effect of surface modification of the nanosponges with heparin on the virus neutralization [ 93 ]. However, the potency of THP-1 mimetics of cytokines neutralization shouldn’t be disregarded.…”

“…However, the potency of THP-1 mimetics of cytokines neutralization shouldn’t be disregarded. Fluorescence spectra using labeled antibodies, such as anti-CD130, anti-CD120a, and anti-CD119 receptors (for IL-6, TNF- α , and IFN- γ , respectively) showed that the surface modification didn’t alter the ability of the monocytes to trap cytokines [ 93 ].…”

Detection, prevention and treatment of COVID‐19 and opportunities for nanobiotechnology

“…Cellular nanosponges composed of polymer cores and cell membranes could simulate host cells, attract, and neutralize SARS‐CoV‐2 through natural cell receptors, thereby generating a broad‐spectrum antiviral strategy 121 . The further increasing of the surface heparin concentration on the cellular nanosponges could promote its inhibitory effect on SARS‐CoV‐2 126 . As the vector of antiviral drugs, nanomaterials cannot only control the release of drugs, but also decrease the side effects by targeted delivery 117,118 …”

“…121 The further increasing of the surface heparin concentration on the cellular nanosponges could promote its inhibitory effect on SARS-CoV-2. 126 As the vector of antiviral drugs, nanomaterials cannot only control the release of drugs, but also decrease the side effects by targeted delivery. 117,118 We can see the successes of nanotechnology-based strategy from detecting, preventing to treating the SARS-CoV-2.…”