Date:15/05/2003 URL: http://www.thehindu.com/2003/05/15/stories/2003051501621300.htm

National

Fight against SARS: anti-cold drug raises hopes

By N. Gopal Raj

THIRUVANANTHAPURAM MAY 14. An anti-cold drug, currently in clinical trials, could probably be modified so that it is effective against the SARS virus, say researchers in Germany.

The German group, which includes two Indians, has studied the structure of the "Main proteinase'' (Mpro) enzyme which plays an important role in the replication of coronaviruses and is therefore attractive as a potential drug target. Their findings are published in the journal, Science.

Kanchan Anand and her colleagues have examined the crystal structure of the Mpro enzyme from a human coronavirus (HCoV) which causes the common cold. They had earlier studied the structure of a pig coronavirus' Mpro. Based on the close similarity of the SARS virus' Mpro to those of the HCoV and the pig virus, the researchers were able to construct a reliable three-dimensional model for the SARS-CoV enzyme.

They then looked at the binding between the pig coronavirus' Mpro and a chemical which inhibits it. Combining this information with their structure of the SARS-CoV Mpro, the German group has suggested that AG7088, a drug currently in clinical trials against the human rhinovirus (one of the causes of the common cold), could be suitably modified to effectively block the SARS virus enzyme.

As there were "some minor clashes'' between AG7088 and the structure of the SARS coronavirus enzyme, the inhibitor was unlikely to be suitable in its present form as a drug against SARS, observes Rolf Hilgenfeld, senior author of the paper from the University of Leubeck in Germany. But since AG7088 is already in clinical trials and there were no cellular enzymes with which it was interfering, the prospects for developing a broad-spectrum antiviral drug were good, the paper noted.

Meanwhile, an international team of researchers has conclusively established that SARS-CoV is indeed what causes the SARS illness. Robert Koch, founder of modern bacteriology, had laid down four conditions, which had to be satisfied to prove that a bacterium was the causative agent of an illness. Two more conditions were subsequently added in the case of viruses.

Three of these conditions have already been satisfied in the case of SARS-CoV, namely isolation of the virus from the diseased hosts, cultivation in host cells and proof of filterability.

A paper being published in the coming issue of Nature says that the remaining three conditions have now been fulfilled. Macaque monkeys infected with the SARS virus derived from a cell culture became ill. The same virus later could be isolated from the monkey's respiratory tract excretions. The monkeys also developed antibodies against the virus.

The SARS coronavirus, therefore, fulfilled all the Koch postulates as the primary cause of SARS. "But this does not exclude the possibility that other pathogens, including human metapneumovirus (hMPV) and Chlamydia pneumoniae, may have exacerbated the disease in some patients,'' the paper added.