Editorial [Hot Topic: SARS-CoV: A Scenario of Modern Drug Design (Executive Editor: X. Huang)]

Infection of viruses usually results in considerable mortality and morbidity worldwide for our human beings. Such as notorious HIV virus, it has imperiled the very fabric of human society as no disease in human history has before. It is estimated that deaths from this pandemic will rival those of the bubonic plague, which killed 93 million people. Epidemic infection of any other viruses has been always a deadly dream in human history. Identified as a novel species of coronavirus, the SARS-CoV has caused severe acute respiratory syndrome (SARS) in late 2002 [1]. Air travel spread it rapidly around the world, and ultimately this virus infected about 8000 people and caused about 800 deaths in 26 countries on 5 continents [2]. Aggressive quarantine measures have successfully terminated the disease, and most likely the virus no longer circulates in the human populations. On the other hand, the battle against virus remains to be everlasting, and top scientists from around the world are committed to develop antiviral drugs and vaccines. At this side, scientists in China together with others involved world-widely have contributed greatly to the latest advances of the scientific studies on SARS-CoV from a number of subjects, leading reasonable drug discovery and design targeting several corresponding key proteins of SARS-CoV. Using multiple strategies, from biochemical investigations to computational simulations, works in the lab of Dr. Xu Shen and Dr. Hualiang Jiang [3] have provided invaluable understanding for the structural and functional characteristics of major proteins responsible for the infection and replication of SARS-CoV, thus vital for the rational drug development and exploration of feasible therapy against this disease. To understand the catalytic mechanism of SARS-CoV, Dr. Luhua Lai [4] focused on the questions about the quaternary structures and substrate selectivity of this target protein using a variety of biophysical and biochemical methods. It is found that this atypical enzyme also follows the general base catalytic mechanism, and some positions at active site are found to be main determinants for substrate specificity as revealed by HPLC assay on synthesized peptides. As performed by Dr. Yexue Li [5], the functional genomics and molecular evolution studies on the SARS-CoV have also found that four proteins were absolutely responsible for nosogenesis of SARS, namely the spike (S) protein; small envelop (E) protien; membrane (M) protein; and nuleocaspid (N) protein. It is also demonstrated that SARS must be originated from wild animals, and particularly the Spike gene, is essential for the transition from animal-to-human transmission to human-to-human transmission. Studies through structural crystallization on various aspects of the main protease, as done in Dr. Zihe Rao's lab [6], have given fundamental insights for both the static and dynamics properties of coronavirus Mpro and functional assignment for different domains. Well-shaping on the catalytic site and substrate binding pocket has laid solid ground for further highly effective and selective inhibitor design against CoV Mpro. It is hopefully to discover a single agent with clinical potential through studies of enzyme activity assay, high-throughput screening, virtual screening and ab initio inhibitor design. As typically done in the area of drug discovery and design, Dr. Roman Osman [7] has performed combinatory computational and biochemical studies on the sweet taste receptor. The reasonable ligand binding sites are identified and verified by convincing site-directed mutagenesis experiments. These studies have led to a better understanding of the structure and function of the sweet taste receptor, and are guiding the rational structural-based design of novel sweeteners, of which could be used in the treatment of human obesity and diabetes. Starting from discovered lead compounds and analogs, Dr. Guangfu Yang [8] provided a unique way of relating the structural descriptors, especially derived from accurate quantum chemistry calculations, with measurable bio-activities. These descriptors cover the features of small molecules from steric, electronic to hydrophobic properties et al., and have been testified as an extension of traditional quantitative structure-activity relationships, also being powerful tools in the design of novel active compounds or positive modification of available low-activity compounds. Finally, I would like to give my sincere thanks to all the authors for their great contributions to this issue mainly focused on SARS-CoV and related advances in modern drug discovery, particularly thanks to Dr. Xu Shen and Dr. Hualiang Jiang for their kindly offering of the cover picture......