title: Development of anti-viral agents using molecular modeling and virtual screening techniques.
abstract: Computational chemistry has always played a key role in anti-viral drug development. The challenges and the quickly rising public interest when a virus is becoming a threat has significantly influenced computational drug discovery. The most obvious example is anti-AIDS research, where HIV protease and reverse transcriptase have triggered enormous efforts in developing and improving computational methods. Methods applied to anti-viral research include (i) ligand-based approaches that rely on known active compounds to extrapolate biological activity, such as machine learning techniques or classical QSAR, (ii) structure-based methods that rely on an experimentally determined 3D structure of the targets, such as molecular docking or molecular dynamics, and (iii) universal approaches that can be applied in a structure- or ligand-based way, such as 3D QSAR or 3D pharmacophore elucidation. In this review we summarize these molecular modeling approaches as they were applied to fight anti-viral diseases and highlight their importance for anti-viral research. We discuss the role of computational chemistry in the development of small molecules as agents against HIV integrase, HIV-1 protease, HIV-1 reverse transcriptase, the influenza virus M2 channel protein, influenza virus neuraminidase, the SARS coronavirus main proteinase and spike protein, thymidine kinases of herpes viruses, hepatitis c virus proteins and other flaviviruses as well as human rhinovirus coat protein and proteases, and other picornaviridae. We highlight how computational approaches have helped in discovering anti-viral activities of natural products and give an overview on polypharmacology approaches that help to optimize drugs against several viruses or help to optimize the metabolic profile of and anti-viral drug.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Chemistry and Pharmacy, University of Innsbruck, Innrain 52, A-6020 Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.forename: Simona
authors.initials: S
authors.lastname: Distinto
authors.forename: Klaus Roman
authors.initials: KR
authors.lastname: Liedl
authors.forename: Patrick
authors.initials: P
authors.lastname: Markt
authors.forename: Judith Maria
authors.initials: JM
authors.lastname: Rollinger
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Gudrun Maria
authors.initials: GM
authors.lastname: Spitzer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003198:Computer Simulation; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D058990:Molecular Targeted Therapy; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001688:Biological Products