Nanotech Antivirals

Most by now will have heard of nanotechnology, although probably rather few actually understand its full implications. There are strict limits to what can be done, and the so-called nanotech that was to be put into vaccines to allow Bill Gates to know where you were is simply not on. (Why anyone would think Bill Gates would care where you are also eludes me.) However, nanotechnology has some interesting uses in the fight against viruses. The Pfizer and Moderna vaccines that use messenger RNA to develop cell resistance, but the RNA is delivered to the cells by being encased in lipid nanoparticles. Lipids are technically and substance from living organisms that are soluble in organic solvents and insoluble in water, but they are often just fats. The lipid breaks open the cell wall, allowing the messenger RNA to get in, and of course that is the method of the virus as well: it is RNA encased in lipid. This technique can be used in other ways, thus such nanoparticles are showing promise for acting as delivery vehicles for other drugs and vaccines.

However, there may be an even more interesting use, as outlined in Nature Biotech. 39: 1172 – 4. The idea is that such nanomaterials could engage with viruses directly, either disrupting them or binding them. A route to disruption may involve nothing more than breaking apart the virus’ outer membrane. The binding approach works because many viruses rely on glycoproteins on their surface to bind to host cells. Anything that can mimic these cellular attachment points can bind the virus, effectively “nanosponges” for mopping them up. One way to make such

 “sponges” something like red blood cells have their contents removed then the remaining membrane is broken into thousands of tiny vesicles about 100 nanometers wide. They then get these vesicles to encase a biocompatible and biodegradable polymer, with the result that each such piece of polymer is coated with genuine cell membrane. Viruses recognize the cell membrane, attach and try to enter the cell, but for them the contents are something of a disappointment and they can’t get back out.

Such membranes obtained from human lung epithelial type II cells, or from human macrophages have angiotensin-converting enzyme 2 (ACE 2)and CD147, both of which SARS-C0V-2 binds to. Potentially we have a treatment that will clean up a Covid-19 infection. According to a study with mice it “showed efficacy” against the virus and showed no evidence of toxicity. Of course, there remains a way to go.

A different approach that shows promise is to construct nano-sized particles that are coated with something that will bind the virus. One example was used in a nasal spray for mice that led to a 99% reduction in viral load when treated with SARS-CoV-2 laden air. It is claimed the particles are not absorbed by the body, although so far the clinical study has not been peer reviewed. The advantage of this approach is that it can in principle be applied to a reasonably wide range of viruses. A further approach was to make “shells” out of DNA, and coat the inner side of these with something that will bind viruses. With several attachment sites, the virus cannot get out, and because of the bulk of the shell cannot bind to a cell and hence cannot infect. In this context, it is not clear whether the other approaches that bind viruses can still infect if the bound virus can attack from its other side.

Many viruses have an outer membrane that is a phospholipid bilayer, and this is essential for the virus to be able to fuse with cell membranes. A further approach is to disrupt the viral membrane, thus stop the fusing. One example is to form a nano-sized spherical surfactant particle and coat it with entities such as peptides that bind to viral glycoproteins. The virus attaches, then the surfactant simply destroys the viral membrane. As can be seen, there are a wide range of possible approaches. Unfortunately, as yet they are still at the preliminary stages and while efficacy has been shown in vitro and in mice, it is unclear what the long-term effects will be. Of course, if the patient is dying of a viral attack, long-term problems are not on his/her mind. One of the side-effects of SARS-CoV-2 may be that it has stimulated genuine research into the topic. This the Biden administration is firing $3 billion at research. It is a pity it takes a pandemic to get us into action, though.