An investigation of the molecular evolution of the severe acute respiratory syndrome (SARS) coronavirus in Guangdong Province, China, provides additional insights into how the virus adapted to life in people after shifting from animals. These results, says Guo-Ping Zhao (Chinese National Human Genome Center and Chinese Academy of Sciences, Shanghai, China), “confirm that this disease is not as infective when it first enters people as it is later in its evolution”.
Many genetic variants of SARS coronavirus have been described since its identification as the SARS causative agent in May 2003. The study of these variants in combination with the epidemiology of the disease, explains Zhao, can provide clues to the biological significance of these variations and may enable us to “take sufficient measures to prevent human transmission from the very beginning of any future outbreak, and then we should be able to prevent an epidemic of the scale we saw in early 2003”.
In its study of 63 SARS-coronavirus sequences (including two from palm civets) from the 2003 epidemic, the consortium divided the epidemic into three phases. In the early phase (Nov 16, 2002-Jan 31, 2003) scattered cases were reported in Guangdong Province. The middle phase (Jan 31-Feb 21) started when a patient admitted to hospital in Guangzhou infected more than 70 people. In the last phase (Feb 21 onwards), a doctor from the hospital apparently carried the virus to Hong Kong.
The researchers report that although single nucleotide variants occurred throughout the epidemic, variants that changed the aminoacid sequence of coding regions arose mainly at the start of the epidemic as SARS coronavirus became adapted to life in its new host. In particular, the sequence of the spike protein, which is important in viral-host recognition and internalisation, was under strong selective pressure early in the epidemic but then stabilised (Science; DOI 10.1126/science.1092002).
“This informative paper provides compelling molecular evidence for animal-to-human transmission of SARS-coronavirus”, says Wayne Marasco (Dana-Farber Cancer Institute, Boston, MA, USA), “and supports the idea that targeting the spike protein with antibody and vaccine therapies may be possible”.
Marasco has recently isolated a human monoclonal antibody directed against the spike protein that can neutralise SARS-coronavirus infection in vitro (Proc Natl Acad Sci USA; DOI 10.1073/pnas.0307140101). “Initial results in animals are encouraging”, he says, “but more experiments are needed to determine whether the antibody will be useful for SARS prophylaxis or early treatment”.