Figure 1.

DENV lifecycle and drug targets. A. DENV enters via receptor-mediated endocytosis. Low pH E rearrangement releases the viral genome. The viral RNA is translated into a polyprotein which is proteolytically processed into the nonstructural proteins after translocation into the Endoplasmic Reticulum (ER). The replication complex is formed and transcription begins. The newly synthesized RNA associates with C and collects prM and E as it buds into the lumen of the ER to form the immature particle. The particle enters the secretory pathway. In the trans-golgi network, prM is clipped by furin but remains associated due to the low pH. In the neutral pH of the extracellular milieu, pr is released, and the now mature virion is capable of infecting a naïve host cell. B. Structure of DENV mature virion (above) and immature particle (below). Figure adapted from Perera et al. (43) copyright 2002 with permission from Elsevier. Also adapted by permission from Macmillan Publishers Ltd: Nature Reviews Microbiology Mukhopadhyay et al. (90), copyright 2005, and partially derived from Miller and Krijnse-Locker (91), copyright 2008. Amended with permission from American Society for Microbiology from Quinkert et al. 2005 (92). PDB identifiers 2BHR, 2J7W, 1L9K, 3C6E.