By Jörg Blech (Der Spiegel)

Virologist Meike Dittmann: „I believe the inhibitor is quite promising in the medium term.”

Effective in 70 percent of cases, in 90 percent, even in 95 percent: The recent triumphant announcements from AstraZeneca, BioNTech and Moderna, rooted in preliminary results from ongoing clinical trials, make it look as though a vaccine against the coronavirus could soon be approved.

But there is another pharmaceutical footrace going on – one which will be just as crucial in the fight against SARS-CoV-2 and other, similar viruses. Largely under the public radar, researchers around the world are searching for a drug therapy to help those who have already contracted the virus. The hope is that patients will be able to take an inhibitor that binds to an important virus enzyme and paralyzes it. That, researchers hope, would then prevent the virus from replicating.

The German virologist Meike Dittmann of the New York University School of Medicine has tested a solution from Pfizer in her laboratory in Manhattan. In a petri dish, it was able to significantly reduce SARS-CoV-2 replication. „I believe the inhibitor is quite promising in the medium term,” Dittmann says.

Other laboratories have also reported encouraging findings. The University of Tübingen is conducting research similar to Dittmann’s, and the German biochemist Christoph Nitsche at Australian National University in Canberra has assembled a team to figure out how to block the important enzyme. The number of experiments with the same focus has exploded around the world.

But what should be the focus of such an agent? SARS-CoV-2 forces its way into host cells and takes control. The cells are reprogrammed and forced to produce viral genetic material and viral proteins – the building blocks of more viruses. A certain enzyme known as a protease, which has the ability to break down proteins, plays a key role here (see graphic).

It is possible to interrupt viral replication at a number of different stages in the process, but many researchers believe that protease present the best target. „It is my favorite target in the life-cycle of the virus,” says Meike Dittmann. „The virus needs the protease immediately after entering the cell, and if the protease is deactivated, the life-cycle is stopped before the virus can even begin to replicate.”

There are other advantages as well. The viral protease is significantly different from proteases found in humans, meaning an inhibitor would likely only bind the correct target. That would make undesirable side effects extremely unlikely. Furthermore, the coronaviruses that have thus far been identified all possess proteases that are more or less identical. That means that an inhibitor developed for SARS-CoV-2 could also be effective against other members of this family of viruses.

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