With a master’s in biology and a diploma in business administration from St. Petersburg University already under his belt, it took ten years for Ukrainian researcher Ievgen Donskyi to start his own research group at Freie Universität Berlin. This is where his journey to becoming an expert in synthetic nanoparticles began with his master’s thesis in polymer science. As a member of Professor Rainer Haag’s working group at the Institute of Chemistry and Biochemistry, he conducted research focused on two-dimensional carbon-based nanomaterials conjugated to polymers mimicking heparan sulfate. These native polysaccharides (which are also present on cell membranes) bind to pathogens via electrostatic interactions, initiating infection. They carry negatively charged sulfate groups that are used to attract viruses, which primarily have positively charged viral envelopes.

“The idea was to simply bind and wrap the viruses using these interactions – kind of like wrapping up a pebble in a sheet of paper,” says Donskyi. That is all well and good – but destroying the pathogens is of course the ultimate goal. This is where a second process involving hydrophobic interactions comes into play. Longer hydrocarbon chains are grafted to the particles. Once captured by the electrostatic interactions, these chains then drill into the virus and rupture the envelope. This lipid membrane is destroyed mechanically so that the virus can no longer reproduce. If viruses were living creatures, you could almost say they’d been stabbed to death.

The Challenges in Developing Antiviral Medication

According to the findings published by the team in 2021, this novel method worked and could be used against the coronavirus. However, they also found that the platform they used – graphene – is unsuitable as the basis for the development of this type of medication, as graphene biologically degrades too slowly and would therefore accumulate in the body. Thankfully, the concept works just as well with black phosphorous, which can be smoothly manufactured from red phosphorous in the lab.

The German Federal Ministry of Education and Research has now awarded his “PathoBlock” project funding worth nearly two million euros over the course of five years.

Ievgen Donskyi has led his own junior research group at the new SupraFAB building at Freie Universität Berlin since the start of the year. But why did they end up focusing on phosphorus? “Black phosphorus is broken down into natural derivatives in the body. This element already makes up about one percent of our body mass and can be found in our bones and teeth. After calcium, phosphorus is the most common mineral found in the body,” says Donskyi. “Previous research has also shown that its metabolized products are biocompatible and nontoxic.”

Zigzagging Nanoparticles

While black phosphorous resembles graphene as they are both thin sheets, its electron structure means that the atoms do not lie on the same plane and that its nanoparticles instead form thin zigzag lattices. This is not visible on a macroscopic level and does not play a role in the composition of phosphorous derivatives. The researchers are able to use particles of a specific size. “We are planning on using particles that are 100–200 nanometers in size. This corresponds more or less to the size of viruses, and our initial tests have shown that it offers the best virus inhibition,” explains Donskyi.

The efficacy of the “stabbing” mechanism – in other words, the carbon chains – depends significantly on their length. “If we use chains with the molecular formula C9H19 for viruses like SARS-CoV-2, then practically nothing happens,” Donskyi says. “But if the chain is just one or two carbon atoms longer – for example C10H21 or C11H23 – then almost all viruses are destroyed. We have already been able to show this in our graphene-based derivatives.” The concept was tested on attenuated corona and herpes viruses in the SupraFAB’s biology lab. Once the best “candidates” have been found, it will be used on real coronaviruses at the Department of Veterinary Medicine.

Research Findings Could Be Applied to Bacteria

Donskyi predicts that the same concept could be used to kill bacteria. “Viruses are easier to destroy because their membrane is thinner, but the basic mechanism could be the same.” However, since bacterial membranes are negatively charged the electrostatic “traps” would have to be positively charged. The particle sizes and chain lengths would also have to be adapted because bacteria are considerably larger than viruses.

What is currently basic research will be further developed so that one day real-world applications will be possible. Donskyi already has a few ideas for how this research could be applied in medications, such as in an antiviral nasal spray or an antibacterial lotion for skin infections. What is fascinating about this project in particular is that in contrast to conventional medications, where the pathogen’s specific binding domain is targeted, the mechanism will work irrespective of the virus or bacteria type. The ultimate goal is to produce broad-spectrum inhibitors that will tackle a wide range of pathogens – including all coronaviruses. This will make them the ideal alternative to conventional antiviral drugs and antibiotics.

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This article originally appeared in German in the Tagesspiegel newspaper supplement published by Freie Universität Berlin.