systematic approaches towards the development of host-directed antiviral therapeutics系统的方法对host-directed抗病毒疗法的发展.pdf

Int. J. Mol. Sci. 2011, 12, 4027-4052; doi:10.3390/ijm OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics Andrew Prussia 1,2, Pahk Thepchatri 1,2,*, James P. Snyder 1,2 and Richard K. Plemper 3,4,* 1 Department of Chemistry, Emory University, Atlanta, GA 30322, USA; E-Mails: aprussi@ (A.P.); jsnyder@ (J.P.S.) 2 Emory Institute for Drug Discovery (EIDD), Emory University, Atlanta, GA 30322, USA 3 Department of Pediatrics, Emory University, Atlanta, GA 30322, USA 4 Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA * Authors to whom correspondence should be addressed; E-Mails: pthepch@ (P.T.); rplempe@ (R.K.P.); Tel.: +1-404-593-0547 (P.T.); +1-404-727-1605 (R.K.P.); Fax: +1-404-727-9223 (P.T.); +1-404-727-9223 (R.K.P.). Received: 27 February 2011; in revised form : 3 June 2011 / Accepted: 3 June 2011 / Published: 15 June 2011 Abstract: Since the onset of antiviral therapy, viral resistance has compromised the clinical value of small-molecule drugs targeting pathogen components. As intracellular parasites, viruses complete their life cycle by hijacking a multitude of host -factors. Aiming at the latter rather than the pathogen directly, host-directed antiviral therapy has emerged as a concept to counteract evolution of viral resistance and develop broad-spect