A small molecule inhibitor of dengue virus type 2 protease inhibits the replication of all four dengue virus serotypes in cell culture

Gubler DJ. The economic burden of dengue. Am J Trop Med Hyg. 2012;86:743–4.

Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: a continuing global threat. Nat Rev Microbiol 2010, Dec Supplement, S7-S16.

Swaminathan S, Khanna N. Dengue: recent advances in biology and current status of translational research. Curr Mol Med. 2009;9:152–73.

Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496:504–7.

Lindenbach BD, Thiel HJ, Rice CM. Flaviviridae: the viruses and their replication. In: Knipe DM, Howley PM, editors. Field’s Virology. 5th ed. Philadelphia: Wolters Kluwer and Lippincott Williams & Wilkins; 2007. p. 1101–52.

World Health Organization: Factsheet No117: Dengue and dengue haemorrhagic fever. 2014. [www.who.int/mediacentre/factsheets/fs117/en/]

Swaminathan S, Batra G, Khanna N. Dengue vaccines: state of the art. Exp Opin Ther Patents. 2010;20:819–35.

Swaminathan S, Khanna N. Experimental dengue vaccines. In: Giese M, editor. Molecular Vaccine-from prophylaxis to therapy. Heidelberg: Springer-Verlag; 2013. p. 135–51.

Capeding MR, Tran NH, Hadinegoro SRS, Ismail HIHJM, Chotpitayasunondh T, Chua MN, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomized, observer-masked, placebo-controlled trial. Lancet. 2014;384:1358–65.

Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomized, controlled phase 2b trial. Lancet. 2012;380:1559–67.

Swaminathan S, Khanna N, Herring B, Mahalingam S. Dengue vaccine efficacy trial: does interference cause failure? Lancet Infect Dis. 2013;13:191–2.

Lim SP, Wang QY, Noble CG, Chen YL, Dong H, Zou B, et al. Ten years of dengue drug discovery: progress and prospects. Antiviral Res. 2013;100:500–19.

Noble CG, Chen YL, Dong H, Gu F, Lim SP, Schul W, et al. Strategies for development of dengue virus inhibitors. Antiviral Res. 2010;85:450–62.

Libraty DH, Endy TP, Houng HSH, Greene S, Kalyanarooj S, Suntayakorn S, et al. Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections. J Infect Dis. 2002;185:1213–21.

Vaughn DW, Greene S, Kalayanarooj S, Innis BL, Nimmanitya S, Suntayakorn S, et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000;181:2–9.

Lescar J, Luo D, Xu T, Sampath A, Lim SP, Canard B, et al. Towards the design of antiviral inhibitors against flaviviruses: the case for the multifunctional NS3 protein from dengue virus as a target. Antiviral Res. 2008;80:94–101.

Falgout B, Miller RH, Lai CJ. Deletion analysis of dengue virus type 4 nonstructural protein NS2b: identification of a domain required for NS2b-NS3 protease activity. J Virol. 1993;67:2034–42.

Chambers TJ, Weir RC, Grakoui A, McCourt DW, Bazan JF, Fletterick RJ, et al. Evidence that the N-terminal domain of nonstructural protein NS3 from yellow fever virus is a serine protease responsible for site-specific cleavage in the viral polyprotein. Proc Natl Acad Sci USA. 1990;87:8898–902.

Chambers TJ, Nestorowicz A, Amberg SM, Rice CM. Mutagenesis of the yellow fever virus NS2b protein: effects on proteolytic processing, NS2b-NS3 complex formation, and viral replication. J Virol. 1993;67:6797–807.

Li J, Lim SP, Beer D, Patel V, Wen D, Tumanut C, et al. Functional profiling of recombinant NS3 proteases from all four serotypes of dengue virus using tetrapeptide and octapeptide substrate libraries. J Biol Chem. 2005;280:28766–74.

Leung D, Schroder K, White H, Fang NX, Stoermer MJ, Abbenante G, et al. Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2b co-factor, small peptide substrates, and inhibitors. J Biol Chem. 2001;276:45762–71.

Yusof R, Clum S, Wetzel M, Murthy HMK, Padmanabhan R. Purified NS2B/NS3 serine protease of dengue virus type 2 exhibits cofactor NS2B dependence for cleavage of substrates with dibasic amino acids in vitro. J Biol Chem. 2000;275:9963–9.

Jean Kumar VU, Poyraz O, Saxena S, Schnell R, Yogeeswari P, Schneider G, et al. Discovery of novel inhibitors targeting the Mycobacterium tuberculosis O-acetylserine sulfhydrylase (CysK1) using virtual high-throughput screening. Biorg Med Chem Lett. 2013;23:1182–6.

Poyraz O, Jeankumar VU, Saxena S, Schnell R, Haraldsson M, Yogeeswari P, et al. Structure-guided design of novel thiazolidine inhibitors of O-acetyl serine sulfhydrylase from Mycobacterium tuberculosis. J Med Chem. 2013;56:6457–66.

Mukhametov A, Newhouse EI, Aziz NA, Saito JA, Alam M. Allosteric pocket of the dengue virus (serotype 2) NS2B/NS3 protease: In silico ligand screening and molecular dynamics studies of inhibition. J Mol Graph Model. 2014;52:103–13.

Othman R, Kiat TS, Khalid N, Yusof R, Newhouse EI, Newhouse JS, et al. Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites. J Chem Inf Model. 2008;48:1582–91.

Korrapati AB, Swaminathan G, Singh A, Khanna N, Swaminathan S. Adenovirus-delivered short hairpin RNA targeting a conserved site in the 5’ non-translated region inhibits all four serotypes of dengue viruses. PLoS Negl Trop Dis. 2012;6:e1735.

Ludert JE, Mosso C, Ceballos-Olvera I, del Angel RM. Use of a commercial enzyme immunoassay to monitor dengue virus replication in cultured cells. Virol J. 2008;5:51.

Schul W, Liu W, Xu HY, Flamand M, Vasudevan SG. A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. J Infect Dis. 2007;195:665–74.

Yildiz M, Ghosh S, Bell JA, Sherman W, Hardy JA. Allosteric inhibition of the NS2b-NS3 protease from dengue virus. ACS Chem Biol. 2013;8:2744–52.

Heaton NS, Perera R, Berger KL, Khadka S, LaCount DJ, Kuhn RJ, et al. Dengue virus non-structural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc Natl Acad Sci USA. 2010;107:17345–50.

Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47:1739–49.