“I do not claim that we predicted the SARS  outbreak, but we did ask ourselved why the human coronaviruses usally do not cause more than a mild form of the common cold.”

In the spring of 2003, the world was shocked by the severe acute respiratory syndrome (SARS) epidemic. Within three weeks after the onset of the simultaneous outbreak in Vietnam, Singapore, and Hong Kong, the agent causing SARS was identified as a new coronavirus. We had just determined the crystal structures of the main proteinases of two coronaviruses that were related to the enzyme from the new SARS virus. In the Science paper, we describe these crystal structures and the construction of a computer model for the SARS virus enzyme. We also propose that a known inhibitor of rhinovirus 3C proteinase, which had already been in clinical trials and was known to be non-toxic, could be a good starting point for the design of anti-SARS drugs. This publication appeared on ScienceXpress within seven weeks of the identification of the new virus. Since then, many research groups have joined the coronavirus research community and are attempting to discover new antiviral therapies. I think our report is very relevant to their work and we are happy that we could make this timely contribution.

It contains in-depth information on the three-dimensional structure of an important enzyme of the SARS coronavirus, which is a very suitable target for antiviral chemotherapy. Without our structural results, no rational design of drugs against this virus (and other members of the coronavirus family) would be possible.

The paper describes the three-dimensional structure of an important enzyme of SARS coronavirus, which is indispensable in viral replication and therefore an ideal target for anti-SARS drugs. It also proposes the use of an existing, and clinically tested, antiviral compound as a starting point for the design of anti-SARS drugs.

I had been interested in cysteine proteinases since my Ph.D. thesis and in antiviral drug design since the start of the HIV pandemic in the mid-1980s. When I became aware of the coronaviruses, they were considered harmless for man, although there were some reports on coronavirus 229E being involved in asthma. However, what I found puzzling was that some animal coronaviruses such as TGEV (infecting piglets) and FIPV (infecting cats) lead to severe sickness and often kills the animals. I do not claim that we predicted the SARS outbreak, but we did ask ourselves why the human coronaviruses usually do not cause more than a mild form of the common cold. In fact, when we applied in the year 2000 to the German Research Foundation (DFG) for a grant in support of our coronavirus research, we did mention that we want to design inhibitors with anticoronaviral activity, and the DFG was wise enough to fund the project. Overall, however, my research into the structures of the coronavirus main proteinases was curiosity-driven—I thought these enzymes were peculiar because they have an additional domain when compared to the distantly related picornavirus 3C proteinases.

This case nicely demonstrates that research cannot always be successfully planned by national or international agencies. In consequence, in addition to coordinated research programs, we need to maintain a culture of curiosity-driven discovery in order to guarantee maximum return on the investment of taxpayers' money into scientific research.