5idk

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Crystal structure of West Nile Virus NS2B-NS3 protease in complex with a capped dipeptide boronate inhibitor

Structural highlights

5idk is a 3 chain structure with sequence from West Nile virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

POLG_WNV Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity).^[1] ^[2] ^[3] ^[4] ^[5] prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity).^[6] ^[7] ^[8] ^[9] ^[10] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).^[11] ^[12] ^[13] ^[14] ^[15] Non-structural protein 1 is involved in virus replication and regulation of the innate immune response (By similarity).^[16] ^[17] ^[18] ^[19] ^[20] Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential).^[21] ^[22] ^[23] ^[24] ^[25] Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity).^[26] ^[27] ^[28] ^[29] ^[30] Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity).^[31] ^[32] ^[33] ^[34] ^[35] Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity).^[36] ^[37] ^[38] ^[39] ^[40] Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity).^[41] ^[42] ^[43] ^[44] ^[45] Non-structural protein 4B inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway (By similarity).^[46] ^[47] ^[48] ^[49] ^[50] RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host JAK1 and TYK2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity).^[51] ^[52] ^[53] ^[54] ^[55]

Publication Abstract from PubMed

A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Structure-activity relationships and a high resolution X-ray cocrystal structure with West Nile virus protease provide a basis for the design of optimized covalent-reversible inhibitors aimed at emerging flaviviral pathogens.

Peptide-Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology.,Nitsche C, Zhang L, Weigel LF, Schilz J, Graf D, Bartenschlager R, Hilgenfeld R, Klein CD J Med Chem. 2016 Dec 14. PMID:27966962^[56]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
↑ Nitsche C, Zhang L, Weigel LF, Schilz J, Graf D, Bartenschlager R, Hilgenfeld R, Klein CD. Peptide-Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology. J Med Chem. 2016 Dec 14. PMID:27966962 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b01021