Viral proteases.

Viruses are major pathogenic agents that can cause a variety of serious diseases in humans, other animals, and plants. Due to their clinical and scientific importance, viruses have been under intensive study ever since their first isolation about a century ago. The studies of viruses, their life cycles, and their interactions with the hosts have established many new areas of biological research over the years. Viruses can be divided into two major categories: enveloped and nonenveloped viruses. Further classification can be based on the nature of the genetic material that is packaged by the virus, for example, single-stranded and double-stranded RNA (ssRNA and dsRNA) viruses and ssDNA and dsDNA viruses. The ssRNA genome can have positive or negative sense, depending on whether it can be directly translated to produce the viral protein. Finally, retroviruses contain a positive-sense RNA genome, but it is reverse-transcribed to DNA during the viral life cycle. Well-known examples of positive-sense ssRNA viruses include picornaviruses (human rhinoviruses and foot-and-mouth disease virus, section III), togaviruses (alphaviruses, section II), and flaviviruses (hepatitis C virus, West Nile virus, and yellow fever virus, section II). Herpesviruses (section VI) and † Phone: (212) 854-5203. Fax: (212) 854-5207. E-mail: tong@ como.bio.columbia.edu. Liang Tong is Associate Professor of Biological Sciences at Columbia University in New York, NY. He received his Ph.D. in 1989 in biophysical chemistry from the University of California at Berkeley, where he studied the structure and function of the proto-oncogene ras p21 in the laboratory of Prof. Sung-Hou Kim. He then did his postdoctoral research with Prof. Michael G. Rossmann at Purdue University, and determined the crystal structure of Sindbis virus capsid protein, which revealed a chymotrypsinlike serine protease. In 1992, he became Senior Scientist (and in 1996 Principal Scientist) at Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, where he continued his research on viral proteases (HIV protease and HCMV protease) and other medically important proteins. He is the recipient of the first Boehringer Ingelheim (Worldwide) Research and Development Award. In 1997, he moved to Columbia University and established a vigorous research program on the structural biology of proteins involved in signal transduction as well as enzymes of medical/ biochemical importance. In addition, he has maintained a strong and continuing interest in the development of new methodology and computer software for protein crystallography. He has been highly productive in his scientific research, and has so far published about 80 papers. 4609 Chem. Rev. 2002, 102, 4609−4626