Special Report - Emerging Viruses

SARS, four years on

Vaccinating chickens against avian flu in the Kulon Progo district of Jakarta, Indonesia, in January 2005. ©FAO/Arif Ariadi Vaccinating chickens against avian flu in the Kulon Progo district of Jakarta, Indonesia, in January 2005.
©FAO/Arif Ariadi
Disinfecting a farm after incinerating infected poultry in Tien Giang province, near Ho Chi Minh City (Vietnam). ©FAO/H.D.Nam Disinfecting a farm after incinerating infected poultry in Tien Giang province, near Ho Chi Minh City (Vietnam).
©FAO/H.D.Nam

We all remember the global SARS (1) epidemic of spring 2003. The immediate fear is past, but the threat remains. A Chinese-European project has set out to discover 50 compounds that can potentially combat the corona virus responsible for SARS.

Remember the breathing masks, the high security at airports, that nagging worry when somebody coughed in the street? Ultimately the much feared catastrophe failed to materialise. The WHO recorded 8 096 SARS cases with 774 deaths between 1 November 2002 and 31 July 2003. These really quite low figures reflect the speedy response of health authorities and scientists. On 12 March, the WHO issued a global pandemic warning; on 27 March, a new type of corona virus (SARS-CoV) was identified as the pathogen; three weeks later its genome had been sequenced; on 5 July the WHO announced that “the worldwide outbreak has been checked.”

Four years later, the anxiety is still there. Experts acknowledge that the disease can re-emerge and that the therapeutic arsenal is still bare. Reviewing the 54 drugs tested at the height of the epidemic, Atlanta’s CDC (Centers for Disease Control and Prevention) found last year that none really proved effective. Worse still, “0.5 % of the Hong-Kong population has now developed an antibody against the virus without actually falling ill. This suggests that the virus is still on the increase – invisibly,” says Rolf Hilgenfeld, director of the Biochemistry Institute at Lübeck University (DE).

Long live curiosity!

As an antivirals specialist, he was in the frontline during the 2003 crisis. It was his team that at the height of the pandemic published the three-dimensional structure of a protein indispensable to SARS-CoV replication, opening the door to SARS drug development. Normally such research can take years. How was he able to publish results just six weeks after the virus was first identified? “This story proves the fact that research cannot be financed solely through wide-ranging programmes planned by government agencies,” he insists. “Research motivated by sheer curiosity must also be encouraged.”

It was this curiosity that since 2000 had led Rolf Hilgenfeld to ask why corona viruses were apparently harmless for human beings, whilst responsible for very dangerous diseases in pigs and cats. He had already started research into the replication mechanisms of these viruses which are pathogenic to animals when the SARS crisis burst out. The urgency of the situation led him to extend the results of his earlier work to the very similar SARS-CoV using computer simulation. His universally acclaimed report published in Science on 13 May 2003 also suggested using the already commercially available AG 7088 compound as the basis for a new drug.

Support from traditional Chinese medicine

With AG 7088 Rolf Hilgenfeld was on the right track. Since then he has teamed up with Polish and Danish laboratories and 4 Chinese institutes in the SEPSDA (Sino-European Project on SARS Diagnostics and Antivirals) project. Together, SEPSDA partners are conducting large-scale research, not just on one protein but on a dozen of the 28 which make up SARS-CoV. With this basic knowledge of the virus’s biochemistry, the project expects to advance both diagnosis and therapy. Thousands of compounds from the traditional Chinese pharmacopoeia are being virtually tested by computer simulation for their ability to block viral enzyme activity. Once a molecule has been deemed promising in silico, it is then subjected to in vitro testing followed by cell culture to prove its ability to stop virus replication. Up to now, 35 or so non-toxic compounds which appear to be effective against the virus have been selected. We await the clinical trials, or the next outbreak of SARS-CoV or another corona virus.

Mikhail Stein

  1. Severe acute respiratory syndrome

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