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

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

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

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

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

11 omote enhanced biochemical activity of JFH-1 NS3.

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

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

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

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

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

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

18 residues within HCV nonstructural protein 3 (NS3) by analyzing diverse sequences of this protein usin

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

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

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

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

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

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

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

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

27 The 99mTc(NS3)(CN-AVP) and 99mTc(NS3)(CN-AVP(an)) ability of binding to small-cell lung c

28 t that the novel vasopressin conjugate 99mTc(NS3)(CN-AVP(an)) is a desirable compound for imaging onc

29 The 99mTc(NS3)(CN-AVP) and 99mTc(NS3)(CN-AVP(an)) ability of bindi

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

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

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

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

34 al chelator (the tris(2-mercaptoethyl)amine (NS3)) and the monodentate isocyanide ligand (CN-peptide)

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

36 lication complex inhibitor), asunaprevir (an NS3 protease inhibitor), and BMS-791325 (a non-nucleosid

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

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

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 ase 3 clinical trials in combination with an NS3 protease inhibitor with ritonavir (r) (ABT-450/r) an

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

44 cific order, with "early" sites (NS1/2-3 and NS3-4) being cleaved rapidly and three "late" sites (NS4

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

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

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

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

49 roteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density.

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

51 a patients was associated with both NS5A and NS3 resistance variants in prior null responders.

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 ntrations that inhibited HCV replication and NS3/4A protease activity.

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

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

57 The intrahepatic immunity of wild-type and NS3/4A-transgenic mice was determined by Western blot, E

58 d viral IAPs, NS1 from Influenza A virus and NS3/4A from Hepatitis C virus.

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

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

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

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

63 aclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor).

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

65 ication complex inhibitor) plus asunaprevir (NS3 protease inhibitor) in patients with genotype 1b inf

66 ference was lost with replication-attenuated NS3-5B JFH1 RNAs, showing that cyclosporine sensitivity

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

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

69 gs, the kinetics of the interactions between NS3 protease inhibitors and enzyme from genotypes 1a, 1b

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

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

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

73 Cleavage by NS3-4A occurs at Cys 11, removing the cytosolic tip of G

74 Thus, cleavage of TCPTP by NS3/4A induces a shift of the intrahepatic immune respon

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

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

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

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

79 n the third, D290N mutation in the conserved NS3 Walker B motif appeared >/=16 days post-transfection

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

81 3 peptide spanning residues 566-585 disrupts NS3-NS5 interaction but not the null-peptide bearing the

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

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

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

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

86 6 (encoding VP6 and NS4), or Seg10 (encoding NS3).

87 Every NS3 and NS5A variant detected at baseline reappeared at

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

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

90 Flavivirus NS3 and NS5 are required in viral replication and 5'-cap

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

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

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

94 al protein NS2B and the protease domain from NS3 (NS3pro).

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

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

97 y available sequences of the genotype 1a HCV NS3 protein, leading to a group of sites for which HCV a

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

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

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

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

102 pentane macrocyclic inhibitors guided by HCV NS3 protease assays, the cellular replicon system, struc

103 ith the approval of the first-generation HCV NS3/4A protease inhibitors.

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

105 simeprevir, a one-pill, once-daily, oral HCV NS3/4A protease inhibitor versus placebo, plus peginterf

106 simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a pl

107 a novel class of achiral peptidomimetic HCV NS3 protease inhibitors.

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

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

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

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

112 vel proviral host factor targeted by the HCV NS3-4A protease.

113 as a bona fide cellular substrate of the HCV NS3-4A protease.

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

115 Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to

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

117 features in the binding of danoprevir to HCV NS3 protease and proved invaluable to our iterative stru

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

119 rrent clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibit

120 Hepatitis C virus (HCV) NS3-4A is required for viral replication and assembly.

121 The hepatitis C virus (HCV) NS3-4A protease is not only an essential component of th

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

123 an oral, once-daily, hepatitis C virus (HCV) NS3/4A protease inhibitor for the treatment of chronic H

124 Telaprevir (TVR), a hepatitis C virus (HCV) NS3/4A protease inhibitor, has been approved to treat ge

125 a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor.

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

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

128 epatic Th1 cells and IFN-gamma(+) T cells in NS3/4A-transgenic mice decreased, whereas the amount of

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

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

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

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

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

134 RASs in NS3 associated with simeprevir or paritaprevir failure i

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

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

137 ts were constructed with coding sequences in NS3/4- and NS6/7-coding regions replaced with sequences

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

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

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

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

142 in mice expressing a functional or inhibited NS3/4A protease to analyze its effect on NS3/4A-mediated

143 not responding to treatment intensification, NS3 resistance variants changed (D168Y to D168T; R155K t

144 Intrahepatic NS3/4A expression made mice resistant to TNF-alpha-induc

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

146 l protein (NS)5A inhibitor ledipasvir (LDV), NS3 protease inhibitor vedroprevir (VDV), non-nucleoside

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

148 ime/MVA boost was demonstrated in a Listeria-NS3-1a challenge model.

149 s the hypersensitivity of neurons to lowered NS3 function.

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

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

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

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

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

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

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

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

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

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

160 ly target only three viral proteins, namely, NS3/4A protease, NS5B polymerase, and NS5A.

161 egion-NS5A (5-5A), which include the natural NS3 protease and NS5A domain-I drug targets.

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

163 absent in a mouse expressing a nonfunctional NS3/4A protease.

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

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

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

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

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

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

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

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

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

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

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

175 ized as an autoprotease that cleaves the NS2/NS3 junction, NS2, primarily via its N-terminal region,

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

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

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

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

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

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

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

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

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

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

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

187 ecombinants allowed for direct comparison of NS3 protease and NS5A inhibitors against HCV strains of

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

189 between the helicase and protease domains of NS3-4A.

190 translated region, and tested the effects of NS3 protease and NS5A inhibitors on these recombinants.

191 an for modulating the enzymatic functions of NS3-4A.

192 re diminished on siRNA-mediated knockdown of NS3.

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

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

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

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

197 leavage, RNA binding, and unwinding rates of NS3 are minimally affected in vitro.

198 The ribosome biogenesis role of NS3 is essential for proper rates of translation in all

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

204 ted NS3/4A protease to analyze its effect on NS3/4A-mediated changes.

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

212 nhibitor of hepatitis c virus (HCV) protease NS3/4A.

213 HCV serine protease NS3 represents an attractive drug target because it is n

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

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

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

217 w levels of the viral nonstructural protein, NS3.

218 presses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B.

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

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

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

222 ulture-adaptive mutations in H77S.2, Q1067R (NS3) had reverted to Q1067 and S2204I (NS5A) was replace

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

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

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

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

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

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

229 We propose that NS3 is the functional ortholog of yeast and human Lsg1,

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

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

232 The NS3 TCR induced a rapid expression of apoptotic signalin

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

234 In addition, the NS3 epitopes used in the recently proposed peptide-based

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

236 t possessed subnanomolar potency against the NS3 protease in a subgenomic replicon-based cellular ass

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

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

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

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

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

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

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

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

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

246 14 affects YFV polyprotein processing at the NS3/4A site.

247 d in a concentration-dependent manner by the NS3 protease inhibitors telaprevir, boceprevir, asunapre

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

249 Cell lines inducibly expressing the NS3-4A protease were analyzed by stable isotopic labelin

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

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

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

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

254 Importantly, the NS3/4A-mediated effects were reversed by ribavirin treat

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

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

257 require mutations after viral passage in the NS3 protease or NS5A domain-I regions targeted by the dr

258 equired for viral RNA replication lie in the NS3-5B region, while virion assembly requires expression

259 with previously identified mutations in the NS3-helicase (F1464L), NS4A (A1672S), and NS5B (D2979G)

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

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

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

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

264 itical regulation of the conformation of the NS3-4A protease and the NS5B polymerase, membrane-bound

265 to identify novel cellular substrates of the NS3-4A protease.

266 tripeptidic acylsulfonamide inhibitor of the NS3/4A enzyme is currently in phase III clinical trials

267 -605339 (35), a tripeptidic inhibitor of the NS3/4A enzyme, is described.

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

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

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

271 therapy against hepatitis C virus target the NS3/4A protease, the NS5A protein, and the NS5B polymera

272 Thus, we conclude that the NS3 linker is critical for mediating protein-protein int

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

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

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

276 munogen is proposed as an alternative to the NS3 epitopes in the peptide-based vaccine IC41.

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

278 nd regulatory approval to market it with the NS3/4A protease inhibitor asunaprevir for the treatment

279 ion systems colocalize, the results point to NS3-5A playing a role in facilitating the integration of

280 R155K residue mutations confer resistance to NS3 protease inhibitors.

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

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

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

284 r notches, no infections were detected using NS3-based ACE.

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

286 type I interferon (IFN), inhibition of viral NS3/4A protease, or a combination of these mechanisms.

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

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

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

290 NS5A resistance variants persisted while NS3 resistance variants generally decayed, suggesting a

291 estored IFN induction after attenuation with NS3/4A protease, a process accompanied by preservation o

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

293 es in specific and discrete interaction with NS3.

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

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

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

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

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

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

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