Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus

The influenza A virus M2 proton channel (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontinued due to widespread drug resistance. Among the handful of drug-resistant mutants, S31N is found in more than 95% of the currently circulating viruses and show...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Proceedings of the National Academy of Sciences - PNAS Ročník 110; číslo 4; s. 1315
Hlavní autori:	Wang, Jun, Wu, Yibing, Ma, Chunlong, Fiorin, Giacomo, Wang, Jizhou, Pinto, Lawrence H, Lamb, Robert A, Klein, Michael L, Degrado, William F
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 22.01.2013
Predmet:	Amantadine - analogs & derivatives Amantadine - chemical synthesis Amantadine - chemistry Amantadine - pharmacology Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Binding Sites Drug Design Drug Resistance, Viral - genetics Genes, Fungal Humans Influenza A virus - chemistry Influenza A virus - drug effects Influenza A virus - genetics Models, Molecular Mutation Nuclear Magnetic Resonance, Biomolecular Recombinant Proteins - antagonists & inhibitors Recombinant Proteins - chemistry Recombinant Proteins - genetics Structure-Activity Relationship Viral Matrix Proteins - antagonists & inhibitors Viral Matrix Proteins - chemistry Viral Matrix Proteins - genetics
ISSN:	1091-6490, 1091-6490
On-line prístup:	Zistit podrobnosti o prístupe
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Abstract	The influenza A virus M2 proton channel (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontinued due to widespread drug resistance. Among the handful of drug-resistant mutants, S31N is found in more than 95% of the currently circulating viruses and shows greatly decreased inhibition by amantadine. The discovery of inhibitors of S31N has been hampered by the limited size, polarity, and dynamic nature of its amantadine-binding site. Nevertheless, we have discovered small-molecule drugs that inhibit S31N with potencies greater than amantadine's potency against WT M2. Drug binding locks the protein into a well-defined conformation, and the NMR structure of the complex shows the drug bound in the homotetrameric channel, threaded between the side chains of Asn31. Unrestrained molecular dynamics simulations predicted the same binding site. This S31N inhibitor, like other potent M2 inhibitors, contains a charged ammonium group. The ammonium binds as a hydrate to one of three sites aligned along the central cavity that appear to be hotspots for inhibition. These sites might stabilize hydronium-like species formed as protons diffuse through the outer channel to the proton-shuttling residue His37 near the cytoplasmic end of the channel.
AbstractList	The influenza A virus M2 proton channel (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontinued due to widespread drug resistance. Among the handful of drug-resistant mutants, S31N is found in more than 95% of the currently circulating viruses and shows greatly decreased inhibition by amantadine. The discovery of inhibitors of S31N has been hampered by the limited size, polarity, and dynamic nature of its amantadine-binding site. Nevertheless, we have discovered small-molecule drugs that inhibit S31N with potencies greater than amantadine's potency against WT M2. Drug binding locks the protein into a well-defined conformation, and the NMR structure of the complex shows the drug bound in the homotetrameric channel, threaded between the side chains of Asn31. Unrestrained molecular dynamics simulations predicted the same binding site. This S31N inhibitor, like other potent M2 inhibitors, contains a charged ammonium group. The ammonium binds as a hydrate to one of three sites aligned along the central cavity that appear to be hotspots for inhibition. These sites might stabilize hydronium-like species formed as protons diffuse through the outer channel to the proton-shuttling residue His37 near the cytoplasmic end of the channel. The influenza A virus M2 proton channel (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontinued due to widespread drug resistance. Among the handful of drug-resistant mutants, S31N is found in more than 95% of the currently circulating viruses and shows greatly decreased inhibition by amantadine. The discovery of inhibitors of S31N has been hampered by the limited size, polarity, and dynamic nature of its amantadine-binding site. Nevertheless, we have discovered small-molecule drugs that inhibit S31N with potencies greater than amantadine's potency against WT M2. Drug binding locks the protein into a well-defined conformation, and the NMR structure of the complex shows the drug bound in the homotetrameric channel, threaded between the side chains of Asn31. Unrestrained molecular dynamics simulations predicted the same binding site. This S31N inhibitor, like other potent M2 inhibitors, contains a charged ammonium group. The ammonium binds as a hydrate to one of three sites aligned along the central cavity that appear to be hotspots for inhibition. These sites might stabilize hydronium-like species formed as protons diffuse through the outer channel to the proton-shuttling residue His37 near the cytoplasmic end of the channel.The influenza A virus M2 proton channel (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontinued due to widespread drug resistance. Among the handful of drug-resistant mutants, S31N is found in more than 95% of the currently circulating viruses and shows greatly decreased inhibition by amantadine. The discovery of inhibitors of S31N has been hampered by the limited size, polarity, and dynamic nature of its amantadine-binding site. Nevertheless, we have discovered small-molecule drugs that inhibit S31N with potencies greater than amantadine's potency against WT M2. Drug binding locks the protein into a well-defined conformation, and the NMR structure of the complex shows the drug bound in the homotetrameric channel, threaded between the side chains of Asn31. Unrestrained molecular dynamics simulations predicted the same binding site. This S31N inhibitor, like other potent M2 inhibitors, contains a charged ammonium group. The ammonium binds as a hydrate to one of three sites aligned along the central cavity that appear to be hotspots for inhibition. These sites might stabilize hydronium-like species formed as protons diffuse through the outer channel to the proton-shuttling residue His37 near the cytoplasmic end of the channel.
Author	Ma, Chunlong Degrado, William F Klein, Michael L Pinto, Lawrence H Wang, Jizhou Wang, Jun Fiorin, Giacomo Wu, Yibing Lamb, Robert A
Author_xml	– sequence: 1 givenname: Jun surname: Wang fullname: Wang, Jun organization: Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158-9001, USA – sequence: 2 givenname: Yibing surname: Wu fullname: Wu, Yibing – sequence: 3 givenname: Chunlong surname: Ma fullname: Ma, Chunlong – sequence: 4 givenname: Giacomo surname: Fiorin fullname: Fiorin, Giacomo – sequence: 5 givenname: Jizhou surname: Wang fullname: Wang, Jizhou – sequence: 6 givenname: Lawrence H surname: Pinto fullname: Pinto, Lawrence H – sequence: 7 givenname: Robert A surname: Lamb fullname: Lamb, Robert A – sequence: 8 givenname: Michael L surname: Klein fullname: Klein, Michael L – sequence: 9 givenname: William F surname: Degrado fullname: Degrado, William F
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23302696$$D View this record in MEDLINE/PubMed
BookMark	eNpNkDtPwzAYRS1URB8wsyGPLCmf7TzssaooIBUYCnPkxDY1SpziBxL8eigUiekeXR3d4U7RyA1OI3ROYE6gYlc7J8OcUFIWtCQEjtCEgCBZmQsY_eMxmobwCgCi4HCCxpQxoKUoJ0hvok9tTF5j6RS2bmsbG-3g8GBw3GqsfHrJvA42ROki3jDygPv0wwfjnuK9326lc7rbt9aZLmn3KfECv1ufwik6NrIL-uyQM_S8un5a3mbrx5u75WKdtQUXMWvbSjWVZFwJRRWtpBQENMlBCcEUN6xSBUhoheG6ymXTMAOmBM5MTrnUis7Q5e_uzg9vSYdY9za0uuuk00MKNaEV44SUnH2rFwc1Nb1W9c7bXvqP-u8a-gXN_mg_
CitedBy_id	crossref_primary_10_1016_j_ejmech_2016_05_008 crossref_primary_10_1016_j_virusres_2013_10_002 crossref_primary_10_1016_j_meegid_2015_05_033 crossref_primary_10_1016_j_drup_2024_101053 crossref_primary_10_1124_mol_119_116640 crossref_primary_10_1038_srep25845 crossref_primary_10_1016_j_bbamem_2016_01_018 crossref_primary_10_1002_ange_201608039 crossref_primary_10_1124_mol_116_105346 crossref_primary_10_1016_j_carres_2020_108088 crossref_primary_10_3390_v10060325 crossref_primary_10_3390_ijms18071554 crossref_primary_10_1038_s41598_018_22875_9 crossref_primary_10_1016_j_antiviral_2020_104780 crossref_primary_10_1002_slct_201901042 crossref_primary_10_1128_JVI_01190_13 crossref_primary_10_1016_j_jbc_2021_100557 crossref_primary_10_1002_cmdc_201500318 crossref_primary_10_1016_j_bbamem_2013_07_033 crossref_primary_10_1016_j_addr_2021_02_007 crossref_primary_10_1073_pnas_1609964114 crossref_primary_10_1128_JVI_00898_16 crossref_primary_10_4155_fmc_14_121 crossref_primary_10_3390_molecules25081937 crossref_primary_10_1007_s11172_023_4057_x crossref_primary_10_1016_j_antiviral_2015_02_004 crossref_primary_10_1111_bph_17317 crossref_primary_10_1073_pnas_1518493112 crossref_primary_10_1111_irv_12549 crossref_primary_10_1002_jmv_27664 crossref_primary_10_1073_pnas_1401997111 crossref_primary_10_1073_pnas_1802177115 crossref_primary_10_1080_13543776_2020_1831471 crossref_primary_10_1007_s00284_021_02661_z crossref_primary_10_1021_ja508461m crossref_primary_10_3389_fchem_2018_00062 crossref_primary_10_1016_j_ejmech_2022_114303 crossref_primary_10_1002_cctc_202000725 crossref_primary_10_1002_anie_201610665 crossref_primary_10_1016_j_antiviral_2018_03_002 crossref_primary_10_1002_cmdc_202300182 crossref_primary_10_1073_pnas_1615471113 crossref_primary_10_1016_j_jmb_2023_167966 crossref_primary_10_1007_s11172_025_4579_5 crossref_primary_10_1016_j_ejmcr_2022_100083 crossref_primary_10_3390_molecules28010147 crossref_primary_10_1021_jacs_5b04802 crossref_primary_10_1128_spectrum_01652_22 crossref_primary_10_1016_j_antiviral_2016_07_019 crossref_primary_10_1021_jacs_9b09985 crossref_primary_10_52711_0974_360X_2022_00820 crossref_primary_10_1099_jgv_0_002133 crossref_primary_10_1007_s11172_024_4297_4 crossref_primary_10_1093_molbev_mst204 crossref_primary_10_3390_ijms231810647 crossref_primary_10_1186_1471_2156_16_S2_S3 crossref_primary_10_1016_j_antiviral_2013_06_006 crossref_primary_10_1128_JVI_00653_15 crossref_primary_10_1016_j_yjsbx_2025_100122 crossref_primary_10_1155_2023_6453969 crossref_primary_10_1534_genetics_116_193979 crossref_primary_10_1021_acs_jmedchem_8b00042 crossref_primary_10_1007_s10989_019_09983_4 crossref_primary_10_1371_journal_pone_0152964 crossref_primary_10_1016_j_tips_2013_08_003 crossref_primary_10_1007_s00203_024_04181_3 crossref_primary_10_1111_tra_12389 crossref_primary_10_1016_j_antiviral_2016_07_024 crossref_primary_10_1016_j_ejmech_2017_04_038 crossref_primary_10_1016_j_bioorg_2020_104106 crossref_primary_10_1099_vir_0_000201 crossref_primary_10_1016_j_tet_2019_06_016 crossref_primary_10_1016_j_coviro_2018_08_007 crossref_primary_10_1016_j_molstruc_2021_131486 crossref_primary_10_1371_journal_ppat_1011993 crossref_primary_10_1016_j_meegid_2018_10_023 crossref_primary_10_3390_pathogens14070608 crossref_primary_10_1134_S1063774523601090 crossref_primary_10_3390_v11050405 crossref_primary_10_1016_j_bbamem_2017_10_026 crossref_primary_10_1371_journal_pone_0199227 crossref_primary_10_1080_22221751_2021_1972769 crossref_primary_10_1016_j_poly_2020_114590 crossref_primary_10_1007_s00044_014_0964_6 crossref_primary_10_3389_fmicb_2022_889643 crossref_primary_10_1016_j_bbamem_2013_09_004 crossref_primary_10_1089_mdr_2015_0297 crossref_primary_10_3390_cells8070654 crossref_primary_10_71267_mencom_7570 crossref_primary_10_3390_molecules27227797 crossref_primary_10_1016_j_bbamem_2025_184456 crossref_primary_10_1002_anie_201608039 crossref_primary_10_3390_pathogens14060599 crossref_primary_10_1002_ange_201610665 crossref_primary_10_1039_D2RA07051K crossref_primary_10_1080_17460441_2019_1560261 crossref_primary_10_1128_JVI_02326_15 crossref_primary_10_1073_pnas_1705624114 crossref_primary_10_3389_fcimb_2019_00067 crossref_primary_10_1021_jacs_8b06741 crossref_primary_10_3390_molecules25122903 crossref_primary_10_1002_pro_2937 crossref_primary_10_2217_fvl_15_95 crossref_primary_10_1007_s11172_015_1035_y crossref_primary_10_7717_peerj_7697 crossref_primary_10_1016_j_coviro_2019_01_006 crossref_primary_10_1002_adsc_201500319 crossref_primary_10_1016_j_ejps_2019_105124 crossref_primary_10_1021_jacs_6b07096 crossref_primary_10_1016_j_jmb_2016_08_007 crossref_primary_10_1021_acs_jmedchem_5b01474 crossref_primary_10_1124_mol_115_102731 crossref_primary_10_1134_S1070428014120239 crossref_primary_10_3389_fmicb_2024_1505203 crossref_primary_10_1128_jvi_00864_24 crossref_primary_10_3390_molecules26040895 crossref_primary_10_1016_j_biocel_2022_106185 crossref_primary_10_1016_j_ejmech_2015_12_013 crossref_primary_10_1039_D2QO01736A crossref_primary_10_1517_17460441_2015_1019859 crossref_primary_10_1007_s00705_019_04386_8 crossref_primary_10_1016_j_apsb_2015_07_006 crossref_primary_10_1021_jacs_9b02196 crossref_primary_10_1007_s00018_014_1615_2 crossref_primary_10_1016_j_toxlet_2014_09_004 crossref_primary_10_1016_j_ijmm_2014_08_016 crossref_primary_10_1002_ejoc_201801285 crossref_primary_10_1007_s10858_013_9745_7 crossref_primary_10_1016_j_bbamem_2013_11_011 crossref_primary_10_1128_jvi_00388_23 crossref_primary_10_1016_j_meegid_2021_105005 crossref_primary_10_1159_000517057 crossref_primary_10_1371_journal_ppat_1008716 crossref_primary_10_1039_D2SC03460C crossref_primary_10_1002_jmv_26670 crossref_primary_10_1039_C6CC02047J crossref_primary_10_3389_fmolb_2021_796229 crossref_primary_10_1002_minf_201400041 crossref_primary_10_1016_j_antiviral_2016_01_012 crossref_primary_10_1080_22221751_2022_2143282 crossref_primary_10_1039_C7RA00305F crossref_primary_10_1016_j_arabjc_2022_103712 crossref_primary_10_1038_s41598_017_01761_w crossref_primary_10_1021_ja4041412 crossref_primary_10_3390_v14030643
ContentType	Journal Article
DBID	CGR CUY CVF ECM EIF NPM 7X8
DOI	10.1073/pnas.1216526110
DatabaseName	Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic
DatabaseTitle	MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	MEDLINE MEDLINE - Academic
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	no_fulltext_linktorsrc
Discipline	Sciences (General)
EISSN	1091-6490
ExternalDocumentID	23302696
Genre	Research Support, Non-U.S. Gov't Journal Article
GrantInformation_xml	– fundername: NIGMS NIH HHS grantid: R01 GM056423 – fundername: NIAID NIH HHS grantid: U01 AI074571 – fundername: NCI NIH HHS grantid: P30 CA060553 – fundername: Howard Hughes Medical Institute – fundername: NIAID NIH HHS grantid: R01 AI020201
GroupedDBID	--- -DZ -~X .55 0R~ 123 29P 2AX 2FS 2WC 4.4 53G 5RE 5VS 85S AACGO AAFWJ AANCE ABBHK ABOCM ABPLY ABPPZ ABTLG ABXSQ ABZEH ACGOD ACHIC ACIWK ACNCT ACPRK ADQXQ ADULT ADXHL AENEX AEUPB AEXZC AFFNX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS AQVQM BKOMP CGR CS3 CUY CVF D0L DCCCD DIK DU5 E3Z EBS ECM EIF EJD F5P FRP GX1 H13 HH5 HYE IPSME JAAYA JBMMH JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST KQ8 L7B LU7 MVM N9A NPM N~3 O9- OK1 PNE PQQKQ R.V RHI RNA RNS RPM RXW SA0 SJN TAE TN5 UKR W8F WH7 WOQ WOW X7M XSW Y6R YBH YKV YSK ZCA ~02 ~KM 7X8
ID	FETCH-LOGICAL-c589t-cc7db7a38d9d2d27aa910e140d993d8f37d50a0c9f8e74abb3f0f6083f428aed2
IEDL.DBID	7X8
ISICitedReferencesCount	204
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000314453900041&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1091-6490
IngestDate	Thu Sep 04 17:54:47 EDT 2025 Mon Jul 21 06:05:44 EDT 2025
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	4
Language	English
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c589t-cc7db7a38d9d2d27aa910e140d993d8f37d50a0c9f8e74abb3f0f6083f428aed2
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
OpenAccessLink	https://www.pnas.org/content/pnas/110/4/1315.full.pdf
PMID	23302696
PQID	1273811683
PQPubID	23479
ParticipantIDs	proquest_miscellaneous_1273811683 pubmed_primary_23302696
PublicationCentury	2000
PublicationDate	2013-01-22
PublicationDateYYYYMMDD	2013-01-22
PublicationDate_xml	– month: 01 year: 2013 text: 2013-01-22 day: 22
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States
PublicationTitle	Proceedings of the National Academy of Sciences - PNAS
PublicationTitleAlternate	Proc Natl Acad Sci U S A
PublicationYear	2013
References	12565051 - J Magn Reson. 2003 Jan;160(1):65-73 12825171 - J Infect Dis. 2003 Jul 1;188(1):57-61 17139286 - Nat Rev Drug Discov. 2006 Dec;5(12):1015-25 19383794 - Proc Natl Acad Sci U S A. 2009 May 5;106(18):7379-84 21094565 - Eur J Med Chem. 2011 Jan;46(1):52-7 21381693 - J Am Chem Soc. 2011 Mar 30;133(12):4274-84 18611380 - Structure. 2008 Jul;16(7):1067-76 21819109 - J Am Chem Soc. 2011 Sep 7;133(35):13844-7 18235503 - Nature. 2008 Jan 31;451(7178):591-5 19223487 - J Gen Virol. 2009 Apr;90(Pt 4):900-8 7688826 - J Virol. 1993 Sep;67(9):5585-94 21359105 - J Phys Chem C Nanomater Interfaces. 2010 Oct 21;114(48):20856-20863 19903212 - Influenza Other Respir Viruses. 2009 Nov;3(6):297-314 21691418 - ACS Med Chem Lett. 2011 Apr 14;2(4):307-312 17160999 - Med Res Rev. 2008 Jan;28(1):1-38 9000633 - J Mol Biol. 1996 Dec 20;264(5):1101-16 16809934 - Intervirology. 2006;49(5):286-93 20130653 - Nature. 2010 Feb 4;463(7281):689-92 15673732 - Antimicrob Agents Chemother. 2005 Feb;49(2):556-9 21744829 - J Am Chem Soc. 2011 Aug 17;133(32):12834-41 19651904 - Antimicrob Agents Chemother. 2009 Oct;53(10):4457-63 18812571 - J Biomol Screen. 2008 Oct;13(9):879-87 4065098 - EMBO J. 1985 Nov;4(11):3021-4 1529523 - Virology. 1992 Sep;190(1):11-8 21550310 - Lancet Infect Dis. 2011 Sep;11(9):677-83 20713739 - Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15409-14 20689043 - Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15075-80 20966252 - Science. 2010 Oct 22;330(6003):509-12 19905033 - Biochemistry. 2009 Dec 22;48(50):11872-82 17522084 - Mol Biol Evol. 2007 Aug;24(8):1811-20 21466220 - J Med Chem. 2011 Apr 28;54(8):2646-57 18235504 - Nature. 2008 Jan 31;451(7178):596-9 17570112 - J Infect Dis. 2007 Jul 15;196(2):249-57 14513385 - J Infect Chemother. 2003 Sep;9(3):195-200 22480220 - J Am Chem Soc. 2012 May 2;134(17):7215-8 20028125 - Biochemistry. 2010 Feb 2;49(4):696-708 12592022 - Protein Sci. 2003 Mar;12(3):520-31 17434944 - Biophys J. 2007 Jul 1;93(1):276-83
References_xml	– reference: 14513385 - J Infect Chemother. 2003 Sep;9(3):195-200 – reference: 19223487 - J Gen Virol. 2009 Apr;90(Pt 4):900-8 – reference: 15673732 - Antimicrob Agents Chemother. 2005 Feb;49(2):556-9 – reference: 21466220 - J Med Chem. 2011 Apr 28;54(8):2646-57 – reference: 18235504 - Nature. 2008 Jan 31;451(7178):596-9 – reference: 17570112 - J Infect Dis. 2007 Jul 15;196(2):249-57 – reference: 4065098 - EMBO J. 1985 Nov;4(11):3021-4 – reference: 21691418 - ACS Med Chem Lett. 2011 Apr 14;2(4):307-312 – reference: 1529523 - Virology. 1992 Sep;190(1):11-8 – reference: 18611380 - Structure. 2008 Jul;16(7):1067-76 – reference: 20713739 - Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15409-14 – reference: 12592022 - Protein Sci. 2003 Mar;12(3):520-31 – reference: 20689043 - Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15075-80 – reference: 18812571 - J Biomol Screen. 2008 Oct;13(9):879-87 – reference: 7688826 - J Virol. 1993 Sep;67(9):5585-94 – reference: 17434944 - Biophys J. 2007 Jul 1;93(1):276-83 – reference: 19383794 - Proc Natl Acad Sci U S A. 2009 May 5;106(18):7379-84 – reference: 17139286 - Nat Rev Drug Discov. 2006 Dec;5(12):1015-25 – reference: 18235503 - Nature. 2008 Jan 31;451(7178):591-5 – reference: 19903212 - Influenza Other Respir Viruses. 2009 Nov;3(6):297-314 – reference: 12825171 - J Infect Dis. 2003 Jul 1;188(1):57-61 – reference: 21359105 - J Phys Chem C Nanomater Interfaces. 2010 Oct 21;114(48):20856-20863 – reference: 21744829 - J Am Chem Soc. 2011 Aug 17;133(32):12834-41 – reference: 17522084 - Mol Biol Evol. 2007 Aug;24(8):1811-20 – reference: 12565051 - J Magn Reson. 2003 Jan;160(1):65-73 – reference: 9000633 - J Mol Biol. 1996 Dec 20;264(5):1101-16 – reference: 16809934 - Intervirology. 2006;49(5):286-93 – reference: 21819109 - J Am Chem Soc. 2011 Sep 7;133(35):13844-7 – reference: 22480220 - J Am Chem Soc. 2012 May 2;134(17):7215-8 – reference: 21094565 - Eur J Med Chem. 2011 Jan;46(1):52-7 – reference: 21381693 - J Am Chem Soc. 2011 Mar 30;133(12):4274-84 – reference: 20966252 - Science. 2010 Oct 22;330(6003):509-12 – reference: 19905033 - Biochemistry. 2009 Dec 22;48(50):11872-82 – reference: 21550310 - Lancet Infect Dis. 2011 Sep;11(9):677-83 – reference: 19651904 - Antimicrob Agents Chemother. 2009 Oct;53(10):4457-63 – reference: 20028125 - Biochemistry. 2010 Feb 2;49(4):696-708 – reference: 17160999 - Med Res Rev. 2008 Jan;28(1):1-38 – reference: 20130653 - Nature. 2010 Feb 4;463(7281):689-92
SSID	ssj0009580
Score	2.5179832
Snippet	The influenza A virus M2 proton channel (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontinued due to...
SourceID	proquest pubmed
SourceType	Aggregation Database Index Database
StartPage	1315
SubjectTerms	Amantadine - analogs & derivatives Amantadine - chemical synthesis Amantadine - chemistry Amantadine - pharmacology Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Binding Sites Drug Design Drug Resistance, Viral - genetics Genes, Fungal Humans Influenza A virus - chemistry Influenza A virus - drug effects Influenza A virus - genetics Models, Molecular Mutation Nuclear Magnetic Resonance, Biomolecular Recombinant Proteins - antagonists & inhibitors Recombinant Proteins - chemistry Recombinant Proteins - genetics Structure-Activity Relationship Viral Matrix Proteins - antagonists & inhibitors Viral Matrix Proteins - chemistry Viral Matrix Proteins - genetics
Title	Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus
URI	https://www.ncbi.nlm.nih.gov/pubmed/23302696 https://www.proquest.com/docview/1273811683
Volume	110
WOSCitedRecordID	wos000314453900041&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings	1
isFullTextHit
isPrint
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1NS8MwGA7qPHhR5-f8IoIHPQTbpm2SkwxxeHBjMJXdRj61oOlc1x389SZth14EwUspJYWSvEmfJ3nf5wHgIhDMweRUIxbrBMUsjBALlC_jIlgHiRaq8lh6fiCDAR2P2bDZcCuatMrlmlgt1CqXfo_8OvQ1JGGYUnwz_UDeNcqfrjYWGqughR2U8SldZEx_iO7SWo2AhSiNWbCU9iH4emp54ZUV0sRRiDD4HV9W_5ne1n-_cBtsNggTduuQaIMVbXdAu5nDBbxshKavdoEeVeKx5UxDbhXM7GsmqgwumBvogCFUs_IFOT7uMaadwxEOB_C9rO6bFv0I-va-fNjqN_80q11PPjnswkU2K4s98NS7e7y9R43tApIJZXMkJVGCcEwVU5GKCOcOUmhHxJTDMooaTFQS8EAyQzWJuRDYBCZ1UM44KsO1ivbBms2tPgRQO94ech1LQkSMuaGKCsOkdJggNZHgHXC-7MqJC2t_VsGtzsti8t2ZHXBQj8dkWutvTCKMHXNk6dEf3j4GG5HPQqk8E09Ay7hJrU_BulzMs2J2VsWLuw6G_S9oMsrV
linkProvider	ProQuest
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Structure+and+inhibition+of+the+drug-resistant+S31N+mutant+of+the+M2+ion+channel+of+influenza+A+virus&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Wang%2C+Jun&rft.au=Wu%2C+Yibing&rft.au=Ma%2C+Chunlong&rft.au=Fiorin%2C+Giacomo&rft.date=2013-01-22&rft.eissn=1091-6490&rft.volume=110&rft.issue=4&rft.spage=1315&rft_id=info:doi/10.1073%2Fpnas.1216526110&rft_id=info%3Apmid%2F23302696&rft_id=info%3Apmid%2F23302696&rft.externalDocID=23302696
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1091-6490&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1091-6490&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1091-6490&client=summon