develops broad-spectrum antiviral drugs. Van Buuren explained: "Essential in the spread of viruses are specific proteases: enzymes that cut virus proteins into the right form, allowing the virus to infect host cells in the body and replicate itself. With protease inhibitors, you can ensure that certain proteases of the virus do not work and prevent the spread of the virus. This makes protease inhibitors an effective antiviral agent."
Until now Protinhi worked on protease inhibitors against flaviviruses. "This is a group of tropical infectious diseases such as dengue, West Nile virus and Zika virus," continued van Buuren. "All viral diseases, transmitted by mosquitoes, still without vaccine and dependent on the same essential protease. With an inhibitor of the shared essential protease, you can tackle the whole group of viruses at once. In that case, we're talking about a broad-spectrum antiviral agent." The technology that Protinhi has developed against flaviviruses in recent years is now being applied to COVID-19 in PanCoroNed.
Van Buuren is convinced that the therapeutic use of protease inhibitors can accelerate the recovery of infected patients. "COVID-19 also has an essential protease. By applying a protease inhibitor as a therapeutic drug, i.e. after infection by the virus, you prevent the virus from multiplying and spreading further throughout the body. A number of already existing viral inhibitors are currently being tested. The best-performing ones accelerate recovery by about thirty percent. When a corona patient is normally in the ICU for ten days, they are now seven. In PanCoroNed we will try to achieve an even more effective protease inhibitor, hopefully resulting in less overloading of the Intensive Cares (IC)".
At the same time, van Buuren continues the work against flaviviruses. "Everyone's very busy fighting the coronavirus, but we're noticing a wave of dengue infections in South America. The shortages in hospitals there are enormous. From our contacts in Brazil, we hear that the combination of COVID-19 and dengue can lead to the need to set up tents there as extra capacity for hospitals. Fighting dengue remains a constant priority for us. The EFRO project 'Tropinhi', in which we have demonstrated that our substances inhibit different flavivirus proteins, is now being completed. In addition, in 2020 we started the Eurostars project 'Flavicure': the follow-up phase for the proof of concept of the broad spectrum principle. With these projects and initiatives, we try to provide the help that is badly needed in the IC's in South America".
Van Buuren believes that protease inhibitors can not only contain the current corona outbreak, but can also play an important role in preventing a future corona-related epidemic. "COVID-19, caused by SARS-CoV-2, is part of a group of coronaviruses. SARS-CoV and MERS-CoV are earlier variants of this and a new coronavirus is bound to appear, let's say SARS-CoV-3. As with flaviviruses, the proteases of different coronaviruses are almost identical. A protease inhibitor against COVID-19 can therefore also be used against this next coronavirus. We can then apply this agent prophylactically, i.e. preventively. People who are particularly vulnerable or who expect to come into contact with the virus, for example, due to age or place of residence, are given the drug in advance and are protected. That way we can prevent another corona pandemic. In PanCoroNed we're going to further elaborate on this as well."
"PanCoroNed is a nice start, but we really see it as a starting point," van Buuren emphasizes. "The five research groups that we can now put to work through this partnership is the first step. Then there are a lot of steps between a proof of concept in the lab and the actual drug at the pharmacy. We must and can be ready for the next virus outbreak, but this requires investment in research and development of virus inhibitors. Both in fundamental academic research and in drug development. Protinhi will, therefore, continue to actively strengthen the current PanCoroNed consortium by means of new subsidies and investments. This is the only way we and other Dutch biotech companies can make a difference and prevent another pandemic."
PanCoroNed is partly the result of the strong cooperation in the Health and High Tech ecosystem of Nijmegen. The links between the partners were quickly established, says van Buuren: "As a spin-out of Erasmus MC and the Institute for Molecules and Materials (IMM) of Radboud University, the next logical step was to settle on Novio Tech Campus. We got to know Avivia, co-initiator of PanCoroNed, because they are on the same floor as us on the campus. In addition, we collaborate with Radboud University and virologists from Leiden UMC and Utrecht University. We have had a good collaboration with the researchers of Radboud University for years. The strong relationship with these partners allowed us to launch PanCoroNed relatively quickly; essential in the fight against viruses".