title: Computational approaches for the discovery of cysteine protease inhibitors against malaria and SARS.
abstract: Cysteine proteases are implicated in a variety of human physiological processes and also form an essential component of the life cycle of a number of pathogenic protozoa and viruses. The present review highlights the drug design approaches utilized to understand the mechanism of inhibition and discovery of inhibitors against protozoal cysteine protease, falcipain (a cysteine protease of P. falciparum which causes malaria), and viral cysteine protease, SARS-CoV M(pro) (a cysteine protease of severe acute respiratory syndrome corona virus). The article describes rational approaches for the design of inhibitors and focuses on a variety of structure as well as ligand-based modeling strategies adopted for the discovery of the inhibitors. Also, the key features of ligand recognition against these targets are accentuated. Although no apparent similarities exist between viral and protozoal cysteine proteases discussed here, the goal is to provide examples of rational drug design approaches adopted to design inhibitors against these proteases. The current review would be of interest to scientists engaged in the development of drug design strategies to target the cysteine proteases present in mammals and other lower order organisms.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Falgun
authors.initials: F
authors.lastname: Shah
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Prashant
authors.initials: P
authors.lastname: Desai
authors.forename: Mitchell
authors.initials: M
authors.lastname: Avery
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000201:enzymology*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000201:enzymology*
chemical_list: D015853:Cysteine Proteinase Inhibitors