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While almost all eyes are focused on vaccines against Covid-19, Protinhi Therapeutics is working on another cure for the pandemic: virus inhibitors. This significantly reduces the severity of the disease course and can prevent a future outbreak. However, there is one problem: the development is slower than hoped because of insufficient resources.

The Nijmegen-based biotech company Protinhi has been working for a few years on virus inhibitors against tropical infectious diseases, such as dengue and the West Nile virus, which recently also occur in the Netherlands. “When Covid-19 showed up, we went straight into our substance library and started looking for compounds that could inhibit this virus,” says Bernd van Buuren, Protinhi’s CEO. “Together with knowledge institutes, we are investigating what works best against this virus and how we can prevent a future outbreak”.

Bernd van Buuren, Protinhi

Van Buuren received a final go from Health Holland for PanCoroNed last summer: a new collaboration between Radboud University in Nijmegen, Utrecht University, Leiden UMC, and the companies Avivia and Protinhi (both located at the Novio Tech Campus in Nijmegen) for the development of virus inhibitors against Covid-19. PanCoroNed is partly the result of the collaboration in the Health and High Tech ecosystem of Nijmegen.

Read more about the Nijmegen-Arnhem-Wageningen region here as #LifePort

Switch off a critical enzyme

Essential in the spread of viruses are proteases, enzymes that adapt proteins in such a way that the virus can multiply and spread in the body. “If you switch off that critical enzyme, it will no longer be able to multiply in the cell and the virus will stop spreading,” Van Buuren explains.

Until recently, Protinhi only worked on virus inhibitors against flaviviruses, including dengue, the West Nile virus, and zika. This is a group of tropical infectious diseases, transmitted by mosquitoes, and there are no vaccines for these diseases. “With an inhibitor that targets the shared essential protease, we can tackle that whole group of viruses in one go.” The technology developed by Protinhi in recent years is now being applied to Covid-19 in PanCoroNed.

Preventing a new pandemic

Now we’re going to quarantine for ten days if you’ve been in contact with someone with Covid-19, but you could also give someone virus inhibitors. Van Buuren: “If you are going to treat someone before or shortly after the infection has taken place, you will prevent someone from becoming seriously ill and the virus from spreading further. A virus inhibitor speeds up recovery”.

A virus inhibitor is not an alternative to a vaccine, but it is a very good addition to fighting a virus. Several existing antiretrovirals have been taken out of the medicine cabinet in recent months to see if they work against covid, such as remdesivir or HIV inhibitors. These drugs have not been developed specifically for Covid-19 and do not appear to work as well. Van Buuren: “If you look where we stand with our research, we have already found compounds that are much more effective than existing virus inhibitors. SARS-CoV-2, the virus that causes Covid-19, is a relatively simple virus. Dengue can be seen as a group of four viruses and the essential protease of dengue is more difficult to tackle with anti-viral agents than the Corona protease”.

Van Buuren believes that anti-viral agents can not only contain the current corona outbreak but can also play an important role in preventing a future corona-related epidemic. Developing a vaccine remains important, but this can only be done once the virus has manifested itself. A virus inhibitor, on the other hand, may already be on the shelf.

“Virus inhibitors can not only contain the current coronary outbreak but can also play an important role in preventing a future corona-related epidemic.”

Bernd van Buuren, Protinhi

“SARS-CoV-2 is part of a group of coronaviruses. SARS-CoV and MERS-CoV are earlier variants 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 virus inhibitor against Covid-19 can therefore also be used against the next coronavirus. By developing this now, a possible next outbreak can be tackled at a much earlier stage”. In short: by investing now we can arm ourselves against future outbreaks.

Insufficient funding

So there’s a reason for hope. But there is a downside as well. “We haven’t yet secured the financing for our corona developments,” says Van Buuren. “If we had the same opportunities as vaccine developers, we would probably have a good virus inhibitor available within a year. Whether you can find the right compound with two or twenty people is quite a difference. We currently have funding from the PanCoroNed consortium to develop a proof-of-concept in the lab, not yet for further research and further development into a drug. With more resources, we could already be in the clinical research phase.”

Protinhi depends on capital from venture investors and receives little extra money from the government for Corona research. “A company like KLM receives billions in government support to stay afloat during the pandemic. It is bitter that for companies and knowledge institutions that may be able to offer a way out of this pandemic it is not possible to receive 10 to 20 million euros because of the state aid rules,” notes Van Buuren with some frustration. “We continue to look for additional subsidies and investors. As a society, we must and can be ready for the next virus outbreak, but this requires investment in research and development of virus inhibitors. It doesn’t help then that an important initiative note to prepare our country for the next pandemic only talks about the development of vaccines and antibiotics. Mind you: both are extremely important, but can’t suppress a virus outbreak. This can be done with virus inhibitors. Leading virologists said this even before the current pandemic”.

“A company like KLM receives billions in government support to stay afloat during the pandemic. It is bitter that for companies and knowledge institutions that may be able to offer a way out of this pandemic it is not possible to receive 10 to 20 million euros because of the state aid rules”.

Bernd van Buuren, Protinhi

Meanwhile, Protinhi also continues its work against flaviviruses. In 2018, 181 people died in Europe from the effects of the West Nile virus and it has recently also occurred in the Netherlands. “Combating dengue and other flaviviruses remains an important priority for us. There is no vaccine against dengue and about 400 million people are infected every year. There is a great need for a drug that helps to fight and cure the disease. We will soon start testing our virus inhibitor in animals. Then comes the clinical phase, before it can be marketed. With the expected positive results, we want to work with a larger pharmaceutical company as soon as possible to go to market with a virus inhibitor”.

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