Based on molecular modeling techniques we constructed a rational 3D model of ORF3 in SARS coronavirus (SARS-CoV). Our studies suggest that the function of ORF3 could be involved in FAD/NAD binding according to its predicted structure and comparison with other structure neighbors. Furthermore, we identified three pairs of non-canonical N–H/p interactions in the structure of ORF3, which can make contributions to the stability of protein structure. These results provide important clues for better understanding of SARS-CoV ORF3 and trying new therapeutic strategies.

The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors.

The main proteinase of SARS-associated coronavirus (SARS-CoV) plays an important role in viral transcription andreplication, and is an attractive target for anti-SARS drug development. The important thing is to understand its binding mechanismwith possible ligands. In this study, we investigated possible noncanonical interactions, potential inhibitors, and bindingpockets in the main proteinase of SARS-CoV based on its recently determined crystal structure. These findings provide a wide clueto searching for anti-SARS drug. Interestingly, we found that similar structure patterns exist in SARS-CoV main proteinase withPoliovirus 3c Proteinase, Rhinovirus 3c Protease, Nsp4 Proteinase From Equine Arteritis Virus, Hepatitis C Virus Ns3 Protease,Hepatitis A Virus 3c Protease, and Dengue Virus Ns3 Protease. It suggests that the available drugs in these viruses could be used tofight SARS disease.

Background: The exact origin of the cause of the Severe Acute Respiratory Syndrome (SARS) isstill an open question. The genomic sequence relationship of SARS-CoV with 30 different singlestrandedRNA (ssRNA) viruses of various families was studied using two non-standard approaches.Both approaches began with the vectorial profiling of the tetra-nucleotide usage pattern V for eachvirus. In approach one, a distance measure of a vector V, based on correlation coefficient wasdevised to construct a relationship tree by the neighbor-joining algorithm. In approach two, amultivariate factor analysis was performed to derive the embedded tetra-nucleotide usage patterns.These patterns were subsequently used to classify the selected viruses.Results: Both approaches yielded relationship outcomes that are consistent with the known virusclassification. They also indicated that the genome of RNA viruses from the same family conformto a specific pattern of word usage. Based on the correlation of the overall tetra-nucleotide usagepatterns, the Transmissible Gastroenteritis Virus (TGV) and the Feline CoronaVirus (FCoV) areclosest to SARS-CoV. Surprisingly also, the RNA viruses that do not go through a DNA stagedisplayed a remarkable discrimination against the CpG and UpA di-nucleotide (z = -77.31, -52.48respectively) and selection for UpG and CpA (z = 65.79,49.99 respectively). Potential factorsinfluencing these biases are discussed.Conclusion: The study of genomic word usage is a powerful method to classify RNA viruses. Thecongruence of the relationship outcomes with the known classification indicates that there existphylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicaseopen reading frames.