Liu: how Singapore scientists tackled SARS

The recent SARS epidemic highlighted the ability of Singapore's science community to rise to the occasion, according to the director of the two-year-old Genome Institute of Singapore (GIS), Edison Liu at the XIX International Congress of Genetics on Wednesday.

Singapore's role in international efforts to understand the deadly SARS coronavirus (SARS-CoV) at a molecular level has included a close look at how the virus has evolved in the months since it first emerged.

Scientists at the GIS sequenced and compared 14 SARS-CoV strains, identifying two distinct genotypes encompassing 16 common mutations. One genotype was designated the North China strain and has been associated with infections in Beijing, Guangzhou and Hong Kong. The other strain, designated the Hotel M contact strain, stemmed from one individual staying at a Hong Kong hotel, who infected people from Singapore, Vietnam and Canada.

Liu said that mutations in the spike protein, a major antigen on the surface of the virus, suggested that the virus was already changing in response to immunological selective pressure. And by comparing strains from different contact generations of the epidemic, the Singaporean researchers found that the virus was mutating rapidly.

"The mutation rate is conservatively one to five mutations per contact generation, so the virus is evolving quickly," Liu said.

Liu said that despite the waning epidemic -- the WHO announced containment of the epidemic this week -- there was a need to remain vigilant, as little was known about the pathobiology of the organism and no effective treatment was available.

Very little is known about the virus reservoir, and how it jumped from its animal host to the human population. While civets and cats have both been implicated, there is still no firm evidence, Liu said. Animals in Singapore's zoo have been screened for evidence of the virus, but no signs have been found, suggesting that SARS has not spread to Singapore's animal population.

"Singapore not only has clean streets, but clean animals in our zoos," Liu joked.

Already the GIS has developed real-time PCR assays capable of measuring the viral load, based on a small, so far non-variable region of the SARS-CoV genome. Liu said the kit would provide a low-cost alternative to commercial kits, and Roche has taken on the distribution role.

In addition, a fast and inexpensive genotyping system, with the ability to genotype hundreds of mutations, and an in vitro culturing system for screening potential antiviral therapies are being developed.

"We desperately need to understand the pathobiology of the infection... and we need an effective antiviral," Liu said. Vaccines are a more difficult issue, with scientists worried that a primed immune response could make the virus more virulent.

Liu said Singapore, having proved the wisdom of its strict public health procedures during the outbreak, is readying itself for a rapid deployment of resources if the virus comes back, with pre-laid plans to test newly developed therapeutics.