ライフサイエンスコーパス: NS3

1 NS3 and NS5 are highly conserved among the four serotype

2 NS3 features two conserved RecA-like domains (D1 and D2)

3 NS3 has NS2B-dependent protease, RNA helicase, and 5'-RN

4 NS3, encoded by Seg-10 of the BTV genome, fulfills key r

5 NS3-dependent cleavage of the HCV polyprotein is require

6 NS3-NS4A evades antiviral innate immunity by inactivatin

7 NS3-NS4A therefore prevents IRF3 activation and interfer

8 ing and duplex unwinding, we show that JFH-1 NS3 binds RNA much more rapidly than the previously stud

9 ike NS3 variants from other genotypes, JFH-1 NS3 binds RNA with high affinity in a functionally activ

10 e other superfamily 2 (SF2) helicases, JFH-1 NS3 does not require long 3' overhangs, and it unwinds d

11 e 1b NS3, which has been well studied, JFH-1 NS3 is a superhelicase with strong RNA affinity and high

12 is, we solved the crystal structure of JFH-1 NS3, revealing a novel conformation that contains an ope

13 omote enhanced biochemical activity of JFH-1 NS3.

14 eveal that the genetic variability of Seg-10/NS3 differentially modulates BTV replication kinetics in

15 ghlights that genetically distant BTV Seg-10/NS3 influence BTV biological properties in a host-specif

16 this study, we revealed that various Seg-10/NS3 proteins alter BTV replication kinetics in mammals b

17 A chimeric GT-1a3a NS3/4A protease amenable to crystallization was engineer

18 Indeed, unlike the inefficient genotype 1b NS3, which has been well studied, JFH-1 NS3 is a superhe

19 d potency of current inhibitors against GT-3 NS3/4A protease is elucidated with structure determinati

20 phism, Q80K, in the nonstructural protein 3 (NS3) gene encoding the viral protease, which has been as

21 y the ATP-dependent nonstructural protein 3 (NS3) helicase.

22 The viral nonstructural protein 3 (NS3) plays a key role in mediating BTV egress as well as

23 protein followed by nonstructural protein 3 (NS3), NS2A, and NS5 were the most targeted proteins.

24 ase domain of viral nonstructural protein 3 (NS3).

25 a helicase known as nonstructural protein 3 (NS3).

26 -terminal domain of nonstructural protein 3 (NS3).

27 o recognize the HCV nonstructural protein 3 (NS3):1406-1415 epitope with high specificity when presen

28 ation and assembly (nonstructural protein 3 [NS3]).

29 The combination of ABT-493 (NS3/4A protease inhibitor) plus ABT-530 (NS5A inhibitor)

30 5G and S1977P only impaired replication as a NS3-5B polyprotein.

31 e of different lethal point mutations across NS3-5B.

32 laprevir 50% effective concentration against NS3 from protease inhibitor-naive patient samples ranged

33 NS4A/2K cleavage sites, resulting in altered NS3-to-NS3-4A ratios.

34 Our analysis predicts that alternative NS3 epitopes may be worth exploring as they might be mor

35 5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasv

36 svir (an NS5A inhibitor) and grazoprevir (an NS3/4A protease inhibitor) are direct-acting antiviral a

37 svir (an NS5A inhibitor) and grazoprevir (an NS3/4A protease inhibitor) are direct-acting antiviral a

38 brentasvir is a fixed-dose combination of an NS3/4A protease inhibitor and an NS5A inhibitor approved

39 vir, an NS5A inhibitor, and paritaprevir, an NS3/4A protease inhibitor dosed with ritonavir, plus rib

40 inhibitor), paritaprevir, and ritonavir (an NS3/4A protease inhibitor)-an interferon- and ribavirin-

41 f 3 weeks of response-guided therapy with an NS3 protease inhibitor and dual NS5A inhibitor-NS5B nucl

42 assessed the impact of different Seg-10 and NS3 proteins on BTV infection and host interactions.

43 ssembly site by interacting with prM, E, and NS3, leading to coordinated C-prM-E cleavage.

44 We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic

45 erved in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups.

46 cant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP

47 en-segmented double-stranded RNA genome, and NS3 proteins are encoded by segment 10 (Seg-10).

48 e protective effects conferred by DJ NS1 and NS3 immunization in the mouse model of DENV infection an

49 protective effects attributed by DJ NS1 and NS3 immunization were demonstrated in a DENV-infected mo

50 l ribosome entry site (IRES) between NS2 and NS3 to separate the two proteins independently of NS2-me

51 hat when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the form

52 line hepatitis C virus (HCV) NS5A, NS5B, and NS3 resistance-associated substitutions (RASs) on respon

53 eplication by HCV NS5BDelta21 polymerase and NS3 helicase.

54 bserved with the copresence of viral RNA and NS3-specific Abs for over 6 months.

55 Our prediction is illustrated using T7 and NS3 helicases as case studies.

56 VP2 and NS3 are primary determinants of BTV pathogenesis, but VP

57 olymorphism that impacts simeprevir, another NS3/4A protease inhibitor.

58 ds targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce ro

59 new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors.

60 l protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside N

61 for a serotype-specific interaction between NS3 and NS5 as well as specific interdomain interaction

62 Lys-330 is required for interaction between NS3 and NS5.

63 In conclusion, PIs and APHIs can block NS3 functions in RNA synthesis and virus assembly, in ad

64 A cis-acting mutation that blocked NS3 helicase activity, T1299A, was tolerated when introd

65 ors (PIs) to the protease active site blocks NS3-dependent polyprotein processing but might impact ot

66 Riplet but does not affect MAVS cleavage by NS3-NS4A.

67 that this pathway is normally inactivated by NS3-NS4A during HCV infection.

68 entrations of HCV NS5A antivirals but not by NS3 protease inhibitors.

69 association with HuR and was upregulated by NS3/4A.

70 We compared NS3, NS5A, and NS5B sequences from 626 patients in Europ

71 Here, we show by competitive NS3-NS5 interaction ELISA that the NS3 peptide spanning

72 omponents of the genome replication complex (NS3, double-stranded RNA, and cellular lipids, including

73 osteric, mostly hydrophobic pocket of dengue NS3 and hold the protease in an open, catalytically inac

74 munity, we further combined DJ NS1 with DENV NS3 to immunize mice and showed activation of Ag-specifi

75 ENV4 NS5 MTase or POL domain or in the DENV2 NS3 helicase domain in the DENV2 chimera RNAs by repeate

76 We further detected NS3-specific CTL activities as well as CD107a expression

77 3 peptide spanning residues 566-585 disrupts NS3-NS5 interaction but not the null-peptide bearing the

78 study, we asked whether genetically distant NS3 proteins can alter BTV-host interactions.

79 nally, the differential behavior of distinct NS3 helicase knockout mutations hints that certain confo

80 se activity of the ZIKV NS3 helicase domain (NS3(Hel)) were investigated in vitro and we demonstrated

81 the biophysical mechanisms for ATPase-driven NS3 helicase function.

82 ith baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both.

83 nt 2 (Seg2, encoding VP2) or Seg10 (encoding NS3) with the BTV8H homologous segments.

84 6 (encoding VP6 and NS4), or Seg10 (encoding NS3).

85 genotype 1 to 6 replicons bearing engineered NS3 resistance-associated substitutions (RASs) were test

86 Every NS3 and NS5A variant detected at baseline reappeared at

87 the smA1' mutant virus that does not express NS3 and NS4 replicated in HAE-ALI as effectively as the

88 Cells expressing NS3/4A and TLR3/MyD88/IFN-beta promoter stimulator 1(-/-

89 nomic replicon RNA or ectopically expressing NS3-4A; and biochemical evidence that NS3-4A cleaves DHC

90 te that, in addition to being a cofactor for NS3 protease, flavivirus NS2B also functions in viral RN

91 CD8 T-cell lines specific for NS3-1073 and NS5-2594 were expanded from HCV-seropositiv

92 ds 51 to 95) alone of NS2B is sufficient for NS3 protease activity, whereas the role of transmembrane

93 quired the other ORF to express a functional NS3-5B.

94 an 8-week regimen combined with grazoprevir (NS3/4A inhibitor; 100 mg once daily) and an NS5A inhibit

95 cacy and safety of grazoprevir (MK-5172; HCV NS3/4A protease inhibitor) and two doses of elbasvir (MK

96 In a trans-complementation assay, an HCV NS3-5A polyprotein precursor was required to facilitate

97 ve treatment duration of grazoprevir (an HCV NS3/4A protease inhibitor) combined with elbasvir (an HC

98 drug regimen of grazoprevir (MK-5172; an HCV NS3/4A protease inhibitor; 100 mg/day) plus ruzasvir (MK

99 ents showing co-occurrence of DHCR24 and HCV NS3-4A protease; formation of an additional, faster-migr

100 d the effect of amino acid variations in HCV NS3 of genotype 1a, 1b, 2b and 3a on NS3-fluoroquinolone

101 667, 101 and 248 nucleotide sequences of HCV NS3 genotypes 1a, 1b, 2b, and 3a, respectively, and tran

102 vergent synthesis of a complex target of HCV NS3/4a protease inhibitor BI 201420 was accomplished.

103 for improving the resistance profile of HCV NS3/4A protease inhibitors.

104 ed genotype 1a-derived HLA-A2-restricted HCV NS3-1073 or NS5-2594 epitope were generated from a genot

105 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide

106 vealed that individual genotype-specific HCV NS3 showed substantial sequence heterogeneity that resul

107 aluating novel antiviral drugs targeting HCV NS3-NS4A protease and T-cell-based HCV vaccines.

108 ion and/or deep sequence analyses of the HCV NS3, NS5A, and NS5B genes were performed on blood sample

109 n intracellular desmosterol, whereby the HCV NS3-4A protease controls activity of 24-dehydrocholester

110 that limits HCV infection.IMPORTANCE The HCV NS3-NS4A protease complex facilitates viral replication

111 ation with genetic vaccines encoding the HCV NS3-NS5b nonstructural proteins during DAA treatment res

112 nhibit and induce the degradation of the HCV NS3/4A protease.

113 specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rec

114 We have used HCV NS3 helicase and fluoroquinolones as a model for drug-pr

115 Hepatitis C virus (HCV) NS3 is a multifunctional protein composed of a protease

116 The hepatitis C virus (HCV) NS3-NS4A protease complex is required for viral replicat

117 ocyclic inhibitor of hepatitis C virus (HCV) NS3/4A protease and was developed for treating chronic H

118 y of a pan-genotypic hepatitis C virus (HCV) NS3/4A protease inhibitor based on a P1-P3 macrocyclic t

119 ity landscape of the hepatitis C virus (HCV) NS3/4A protease, whose function-site-specific cleavages

120 member of the superfamily 2 (SF2) helicases, NS3 requires the binding and hydrolysis of ATP/NTP to tr

121 anner and increases our understanding of how NS3 proteins contribute to the outcome of BTV infection.

122 n) showed that positions 56, 156, and 168 in NS3 were most impactful because they diminished protein-

123 sistent with the detection of R155K/D168A in NS3 from virologic failures treated with simeprevir but

124 tance-associated substitutions identified in NS3 from GT1a-infected patients who failed therapy with

125 diated by a negatively charged RLDP motif in NS3 that is conserved in ZIKV strains of African and Asi

126 ighly conserved phosphomimetic RxEP motif in NS3 was essential for the binding of 14-3-3varepsilon.

127 wild type (WT) and compensatory mutations in NS3 gene appeared.

128 typic recombinants via adaptive mutations in NS3 protease or helicase domains.

129 r interactions of PI resistance mutations in NS3-4A can impact protease functional sites dependent on

130 with protease inhibitors, 53.7% had RASs in NS3 and 96.5% achieved an SVR12.

131 RASs in NS3 associated with simeprevir or paritaprevir failure i

132 We compared RASs in NS3, NS5A, and NS5B among patients failed by DAA therapy

133 RAVs in NS3, NS5A, and NS5B were detected by population-based se

134 rgent resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients with tre

135 d for resistance-associated substitutions in NS3 and NS5A.

136 uired resistance-associated substitutions in NS3 and/or NS5A.

137 nd that the T407A and S411A substitutions in NS3 reduce viral replication and increase the helicase-u

138 more, we identified 2 other substitutions in NS3 that may interact with Q80K and contribute to its st

139 t the role of the host-specific variation in NS3 protein turnover rate.

140 th reduced susceptibility to DAAs, including NS3/4A protease inhibitors such as voxilaprevir.

141 rect-acting antivirals against HCV including NS3/4A protease inhibitors (PIs) has greatly improved tr

142 is sensor containing the flavivirus internal NS3 cleavage site linker reported the highest fluorescen

143 Its NS3 helicase domain plays critical roles in NTP-dependen

144 NS3(172-618) helicase and covalently linked NS3(172-618)-NS5(320-341) reveals a rigid and compact fo

145 mly assigned to receive grazoprevir (100 mg, NS3/4A protease inhibitor) and elbasvir (50 mg, NS5A inh

146 ngs: those requiring expression of a minimum NS3-5A and those requiring expression of a minimum NS3-5

147 h K1240N inhibiting replication as a minimum NS3-5A polyprotein whereas V1665G and S1977P only impair

148 and those requiring expression of a minimum NS3-5B polyprotein.

149 -derived vesicular structures induced by MNV NS3 were highly motile and dynamic in nature, and their

150 in, an indicator of cholesterol content, MNV NS3 displayed a greater association with flotillin and s

151 served that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced

152 is study reveals that murine norovirus (MNV) NS3 is intimately associated with the viral replication

153 NAJC14's folding activity normally modulates NS3/4A/2K cleavage events to liberate appropriate levels

154 Furthermore, an S1977P-mutated NS3-5A polyprotein complemented other defects shown to b

155 al-time live-cell reporter, termed the NIrD (NS3-4A Inducible rtTA-mediated Dual-reporter) system, wh

156 redominantly on the capsid and nonstructural NS3 and NS5 antigens.

157 Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimatel

158 ighlight the conserved properties of the NoV NS3 proteins among the seven Norovirus genogroups.

159 and the 3'-UTR and, similar to HCV, the NPHV NS3-4A protease can cleave mitochondrial antiviral-signa

160 TCRs) recognizing the HCV nonstructural (NS) NS3 or NS5 viral peptide target were examined by mRNA tr

161 (+) T cells targeting the nonstructural NS1, NS3, and NS5 proteins of TDV-2.

162 oV1-encoded nonstructural proteins NS1, NS2, NS3, and NP1 but not NS4.

163 found that the other NS proteins (NS1, NS2, NS3, and NS4) are not required for the expression of VP

164 The novel small NS proteins (NS2, NS3, and NS4) were confirmed to be expressed following t

165 udy identified three novel NS proteins, NS2, NS3, and NS4, and suggests an important function of the

166 NA replication and virus assembly, i.e., NS2-NS3 autoprocessing and E2 recruitment to the DRM, are re

167 ase is responsible for autoprocessing of NS2-NS3 precursor, an essential step in HCV RNA replication.

168 cal for HCV RNA replication by promoting NS2-NS3 autoprocessing.

169 ntroducing an NS2/C113S mutation reduced NS2-NS3 autoprocessing and impaired HCV RNA replication.

170 direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design.

171 tly located within 80 amino acids of the NS2/NS3 junction.

172 None of the mutations affected NS2B-NS3 protease activity.

173 so recruits the C-prM-E polyprotein and NS2B-NS3 protease to the virion assembly site by interacting

174 The highly conserved Flavivirus NS2B-NS3 protease is essential for viral replication and ther

175 to detect the activities of flavivirus NS2B-NS3 serine proteases in living cells.

176 Similar to ZIKV infection, NS2B-NS3 expression led to cytokinesis defects and cell death

177 disorderness of NS2B cofactor region of NS2B-NS3 protease.

178 Among binding partners, NS2B-NS3 cleaved Septin-2, a cytoskeletal factor involved in

179 e describe a role for the ZIKV protease NS2B-NS3 heterodimer in mediating neurotoxicity through cleav

180 aviviruses is the viral serine protease NS2B-NS3.

181 Nile virus is the viral serine protease NS2B-NS3.

182 We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical scre

183 h is demonstrated with the dengue virus NS2B-NS3 protease in complex with a high-affinity ligand cont

184 nhibitors of dengue and West Nile virus NS2B-NS3 protease.

185 virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development

186 losteric site shared between flaviviral NS2B/NS3 proteases is presented whose efficacy is demonstrate

187 The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses

188 ubstrate cleavage sites by dengue virus NS2B/NS3 protease.

189 inhibitor able to target both the virus NS5-NS3 interaction and the host kinases c-Src/Fyn.

190 not NS5A(S25-K215), enabled the NS5BDelta21-NS3 helicase complex to be stably associated with the te

191 ribution of MNV and NV NS3s were similar, NV NS3 displayed a higher level of colocalization with the

192 by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a withou

193 I1373-1380 located in the helicase domain of NS3 in people who inject drugs (PWID) exposed predominan

194 age events to liberate appropriate levels of NS3 and NS4A and promote RC formation.

195 ntains potent activity against a majority of NS3 resistance-associated amino acid substitutions, incl

196 This work reveals that DNAJC14 modulation of NS3/4A site processing is an important mechanism to ensu

197 they rapidly engage with and block a pool of NS3 involved in assembly.

198 serotypes within the immunogenic regions of NS3, NS4B and NS5.

199 dy reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV in

200 analysis revealed a pre-activation state of NS3 helicase in complex with GTPgammaS, in which the tri

201 tructure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as

202 Our understanding of NS3 from the highly active HCV strains that are used to

203 in HCV NS3 of genotype 1a, 1b, 2b and 3a on NS3-fluoroquinolone interaction.

204 ented other defects shown to be dependent on NS3-5A for rescue.

205 Small angle x-ray scattering study on NS3(172-618) helicase and covalently linked NS3(172-618)

206 ortance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants fr

207 Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic

208 sbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpa

209 mbitasvir (NS5A inhibitor) and paritaprevir (NS3/4A protease inhibitor; co-dosed with ritonavir) plus

210 t here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-A resolution.

211 the NS4A transmembrane domain that prevents NS3-NS4A targeting of Riplet but not MAVS.

212 ZIKV produced NS3 and E proteins and generated higher viral titers in

213 The protease NS3/4A from hepatitis C virus redistributes the complexe

214 expression of the hepatitis C virus protease NS3/4A, which efficiently cleaves TRIF and IFN-beta prom

215 HCV nonstructural protein NS3/4A interacts with CHK2 and downregulates its activit

216 w levels of the viral nonstructural protein, NS3.

217 Dengue virus multifunctional proteins NS3 protease/helicase and NS5 methyltransferase/RNA-depe

218 in) fused to the nonstructural (NS) proteins NS3-NS5B from RHV (ChAd-NS) was used to vaccinate Spragu

219 The hepatitis C viral proteins NS3/4A protease, NS5B polymerase, and NS5A are clinicall

220 Like many viral proteins, NS3 is multifunctional, but how PIs affect stages of the

221 btype-specific role for the protease residue NS3-Q80 in molecular mechanisms related to the assembly

222 he replicon system, we show that the RHV-rn1 NS3-4A protease cleaves a human mitochondrial antiviral

223 ChAd-NS or with a plasmid encoding the same NS3-NS5B antigens increased efficacy to 100% and 83%, re

224 w model where an LGP2-MDA5 oligomer shuttles NS3 to the mitochondria to block antiviral signaling.

225 Significantly, NS3:Asn-570 to alanine mutation introduced into an infec

226 ed difference in the clinical impact of some NS3 substitutions was investigated.

227 at FAM E3 could indeed bind to and stabilize NS3(Hel).

228 uch more rapidly than the previously studied NS3 variants from genotype 1b.

229 gesting that flaviviruses may use suboptimal NS3 helicase activity for optimal genome replication.

230 Subsequently, NS3 is recruited to the replication complex by NS5BDelta

231 itro and in vivo We further demonstrate that NS3-4A cleaves DHCR24 between residues Cys(91) and Thr(9

232 Together, these studies demonstrate that NS3-4A directly cleaves DHCR24 and that this results in

233 essing NS3-4A; and biochemical evidence that NS3-4A cleaves DHCR24 to produce DHCR24* in vitro and in

234 Notably, we found that NS3 protein turnover may vary in ovine but not in Culico

235 Overall, these data indicate that NS3 motif V may play a role in the pathogenesis, dissemi

236 We show that NS3/HLA-A2 recognition by the HCV1406 TCR is critically

237 T-PCR for the NS3:N570A mutant suggests that NS3-NS5 interaction plays an important role in the balan

238 The NS3 protease regions of viruses belonging to 6 genotypes

239 The NS3 TCR induced a rapid expression of apoptotic signalin

240 The NS3/4A protease of hepatitis C virus (HCV) is an importa

241 overexpressed wild-type DNAJC14 affected the NS3/4A and NS4A/2K cleavage sites, resulting in altered

242 features unique to both the allo-MHC and the NS3 epitope.

243 Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 o

244 vir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepat

245 vir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients.

246 with the NS5A inhibitor velpatasvir and the NS3/4A protease inhibitor GS-9857, in patients with hepa

247 essential for viral replication, such as the NS3 helicase.

248 erone function to modulate processing at the NS3/4A site as a mechanism ensuring virus replication.

249 e introduced amino acid substitutions at the NS3/4A site to alter the levels of the NS3 and NS4A prod

250 wild-type arginine or lysine residue at the NS3/4A site were obtained.

251 14 affects YFV polyprotein processing at the NS3/4A site.

252 of which produced a clinical candidate: the NS3 protease inhibitor asunaprevir (64), marketed as Sun

253 l remain unclear, including the role for the NS3 protein, one of seven nonstructural viral proteins,

254 nd RNA synthesis by real time RT-PCR for the NS3:N570A mutant suggests that NS3-NS5 interaction plays

255 e around the pinpointed amino acids from the NS3 and NS5 regions are also conserved.

256 tis C virus (HCV) requires proteins from the NS3-NS5B polyprotein to create a replicase unit for repl

257 common ancestry with the Flaviviridae in the NS3 and NS5 regions.

258 the NS4B5A boundary (S1977P), another in the NS3 helicase (K1240N), and a third in NS4A (V1665G).

259 in, 5 hinge regions in the NS2B bound in the NS3 protease complex and 5 hinges in the NS3- helicase p

260 ween rs12979860 genotype and variants in the NS3, NS4A, NS5A and NS5B HCV proteins.

261 the NS3 protease complex and 5 hinges in the NS3- helicase protein.

262 A variety of amino acid substitutions in the NS3-4A protease of the hepatitis C virus lead to proteas

263 replication by a noncytotoxic mechanism, the NS3-specific TCR-redirected CTLs were polyfunctional and

264 t the NS3/4A site to alter the levels of the NS3 and NS4A products and examined their effects on YFV

265 In particular, one of the NS3 proteins analyzed harbored a proline at position 24

266 Deep sequencing of the NS3, NS5A, and NS5B regions were performed at baseline,

267 ety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhib

268 s approach, we showed that, depending on the NS3 considered, BTV replication kinetics varied in mamma

269 he allosteric modulation of MgNTP(2-) on the NS3 helicase activity.

270 cting antiviral agent (DAA) that targets the NS3/4A protease of hepatitis C virus (HCV).

271 mpetitive NS3-NS5 interaction ELISA that the NS3 peptide spanning residues 566-585 disrupts NS3-NS5 i

272 Here we found that the NS3 protein of dengue virus (DV) bound to 14-3-3varepsil

273 We show that the NS3 protein of Zika virus (ZIKV) antagonizes antiviral g

274 We observed that the NS3 proteins of both MNV and Norwalk virus (NV) induce p

275 response at 12 weeks (SVR12) rate using the NS3/4A protease inhibitor grazoprevir and the NS5A inhib

276 Viruses resistant to NS3-4A protease inhibitors disappear from peripheral blo

277 cleavage sites, resulting in altered NS3-to-NS3-4A ratios.

278 Unlike NS3 variants from other genotypes, JFH-1 NS3 binds RNA w

279 otein that functions as a cofactor for viral NS3 protease.

280 the underlying mechanism involves the viral NS3/4 protease and the cohesin regulator, WAPL.

281 covery of a back-up to the hepatitis C virus NS3 protease inhibitor asunaprevir (2) is described.

282 l substrate motifs for the hepatitis C virus NS3/4 protease using an in vivo assay.

283 chment of desmosterol in the membranes where NS3-4A and DHCR24 co-occur.

284 We therefore set out to determine whether NS3 from the replicatively efficient genotype 2a strain

285 ecific CD8 T cell response was diverse, with NS3-specific cells being the most dominant.

286 es in specific and discrete interaction with NS3.

287 chy of the DENV nonstructural proteins, with NS3, NS5, and NS1 being dominant in both donor cohorts.

288 revir susceptibilities of HCV replicons with NS3 RASs were dependent on subtype background and the ty

289 avior--a characteristic probably shared with NS3 helicases from all Flaviviridae members--that could

290 TP hydrolysis and helicase activities within NS3 and provide insight into the biophysical mechanisms

291 ch mutant to probe structural changes within NS3 caused by each mutation.

292 these distinct regulatory mechanisms within NS3-NS4A and defines a new role for Riplet in the antivi

293 n IFNL4 SNPs and rare and common RAVs within NS3 and NS5B.

294 Those within NS3 and NS5 are located at the surface and/or within the

295 NS4B protein), and the immunorecessive YTM9 (NS3 protein)-and used these TCRm mAbs to stain WNV-infec

296 ZIKV NS3 is sufficient to inhibit the RLR-14-3-3e/eta interac

297 ow cytometry staining for intracellular ZIKV NS3, using a ZIKV-specific polyclonal antibody.

298 Data showed that ZIKV NS3 antigen could be detected in CD45+CD14+ monocytes.

299 tability and the ATPase activity of the ZIKV NS3 helicase domain (NS3(Hel)) were investigated in vitr

300 predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one p