Multi-Omics Studies towards Novel Modulators of Influenza A Virus-Host Interaction.
Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV-host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the 665 remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating properties of these compounds and their combinations as well as potential viral and host resistance to them may lead to the discovery of novel modulators of IAV-host interactions, which might be more effective than the currently available anti-influenza therapeutics.
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland. sandra.soderholm@helsinki.fi.|Finnish Institute of Occupational Health, Helsinki 00250, Finland. sandra.soderholm@helsinki.fi.
Sandra
S
Söderholm
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. yu.fu@helsinki.fi.
Yu
Y
Fu
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. lgaelings@stud.hs-bremen.de.
Lana
L
Gaelings
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. sergei.belanov@helsinki.fi.
Sergey
S
Belanov
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. yetulax@mappi.helsinki.fi.
Laxman
L
Yetukuri
Institute of Mathematics and Computer Science, Ural Federal University, Yekaterinburg 620083, Russia. berlm@mail.ru.
Mikhail
M
Berlinkov
Q-Mol L.L.C. in Silico Pharmaceuticals, San Diego, CA 92037, USA. anton.cheltsov@gmail.com.
Anton V
AV
Cheltsov
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. simon.anders@fimm.fi.
Simon
S
Anders
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. tero.aittokallio@fimm.fi.|Department of Mathematics and Statistics, University of Turku, Turku 20014, Finland. tero.aittokallio@fimm.fi.
Tero
T
Aittokallio
Institute of Clinical Medicine, Oslo 0450, Norway. t.a.nyman@medisin.uio.no.
Tuula A
TA
Nyman
Finnish Institute of Occupational Health, Helsinki 00250, Finland. sampsa.matikainen@helsinki.fi.|Department of Rheumatology, Helsinki University Hospital, University of Helsinki, Helsinki 00015, Finland. sampsa.matikainen@helsinki.fi.
Sampsa
S
Matikainen
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. denis.kainov@helsinki.fi.
Denis E
DE
Kainov
antiviral agent; genomics; influenza virus; metabolomics; phosphoproteomics; proteomics; transcriptomics; virtual ligand screening
Influenza Other Respir Viruses. 2007 Sep-Nov;1(5-6):189-92
19453426
Viruses. 2015 Dec 25;8(1):null
26712783
Mol Cell Proteomics. 2016 Oct;15(10 ):3203-3219
27486199
Microbes Infect. 2006 Jul;8(8):2262-9
16793312
Int J Mol Sci. 2013 Feb 19;14(2):4148-62
23429198
Cell Immunol. 1985 Mar;91(1):227-39
2982505
PLoS One. 2013;8(4):e60792
23577160
J Biol Chem. 2014 Sep 12;289(37):25405-17
25065577
Res Virol. 1995 Mar-Apr;146(2):141-9
7638438
Planta Med. 2001 Aug;67(6):548-9
11509977
Immune Netw. 2013 Apr;13(2):70-4
23700397
Antiviral Res. 2016 May;129:21-38
26872862
Brain Res. 1997 Nov 21;776(1-2):96-104
9439800
J Virol. 1995 Apr;69(4):2306-12
7884876
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
16199517
PLoS One. 2013 Jun 13;8(6):e66546
23785507
Virology. 2013 Nov;446(1-2):180-8
24074580
J Biol Chem. 2012 Oct 12;287(42):35324-32
22910914
Curr Pharm Des. 2007;13(4):405-14
17311557
Med Res Rev. 2014 Mar;34(2):301-39
23801557
PLoS Pathog. 2016 May 11;12(5):e1005615
27168185
PLoS One. 2015 May 18;10(5):e0127086
25985305
Genome Biol Evol. 2015 Nov 27;7(12 ):3472-83
26615216
Innate Immun. 2013 Oct;19(5):531-44
23405029
PLoS One. 2013 Sep 26;8(9):e76560
24086750
Virol J. 2006 May 29;3:39
16729896
Med Microbiol Immunol. 2015 Dec;204(6):635-45
25680890
Nat Commun. 2013;4:2763
24434940
Crit Care. 2013 Dec 27;17(6):R301
24373231
Int J Mol Med. 2014 Jul;34(1):61-73
24788303
Yao Xue Xue Bao. 2015 Aug;50(8):966-72
26668995
Biomed Res Int. 2015;2015:675149
25710018
J Virol. 2010 May;84(9):4673-81
20181696
Antiviral Res. 1995 Aug;27(4):425-30
8540761
J Med Virol. 2013 Nov;85(11):1978-82
23926054
J Med Virol. 2015 Jul;87(7):1096-103
25715935
J Agric Food Chem. 2011 Dec 28;59(24):12858-63
22047208
Virology. 2016 Jan;487:85-94
26499045
Trends Pharmacol Sci. 2012 Feb;33(2):89-99
22196854
Acta Virol. 1982 Jul;26(4):209-16
6127927
Sci Rep. 2015 Feb 17;5:8517
25687228
Molecules. 2011 Feb 28;16(3):2032-52
21358592
Transplantation. 1986 Oct;42(4):376-9
3532450
Arch Virol. 2016 Feb;161(2):345-51
26559961
Virology. 2013 Apr 25;439(1):42-6
23453580
Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):853-7
9517602
Proteomics. 2008 May;8(9):1851-8
18398875
Autoimmunity. 2011 Nov;44(7):562-70
21838592
J Biol Chem. 2014 Apr 25;289(17):11986-92
24627473
J Virol. 2012 Oct;86(19):10704-13
22837202
Acta Virol. 1982 May;26(3):125-9
6127012
Bioinformatics. 2009 Jun 15;25(12):i145-53
19477980
Exp Lung Res. 2005 Jun;31(5):449-59
16019982
Mol Immunol. 2015 May;65(1):1-16
25597246
Nucleic Acids Res. 2009 Jan;37(1):1-13
19033363
Cytokine Growth Factor Rev. 2001 Jun-Sep;12(2-3):171-80
11325600
Cell Death Differ. 2016 Jul;23(7):1243-56
26943321
Sci Rep. 2014 Jan 21;4:3799
24445954
Am J Physiol Lung Cell Mol Physiol. 2015 Feb 1;308(3):L270-86
25361566
J Negat Results Biomed. 2011 May 09;10:5
21554703
J Virol. 2012 May;86(10):5422-36
22398282
Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2):349-54
17624247
J Virol. 2010 Jun;84(11):5574-82
20335267
Acta Microbiol Pol. 1984;33(1):51-5
6205551
J Biol Chem. 1982 Mar 25;257(6):2795-801
7061450
Int J Clin Exp Med. 2014 Dec 15;7(12):5593-602
25664078
Cell Mol Life Sci. 2014 Oct;71(19):3659-83
24699705
Immunity. 2011 Jun 24;34(6):854-65
21703540
Clin Pharmacol Ther. 2010 Apr;87(4):437-44
20182424
J Pharmacol Exp Ther. 2010 Apr;333(1):81-90
20040578
Cell Death Dis. 2013 Jul 25;4:e742
23887633
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11790-5
18689690
J Med Virol. 1980;6(2):169-74
7241092
Vaccine. 2014 Sep 22;32(42):5411-9
25131731
Ann Glob Health. 2015 Sep-Oct;81(5):645-53
27036721
Hum Immunol. 2010 Jan;71(1):14-22
19748539
Antiviral Res. 2016 Sep;133:23-31
27451344
Arzneimittelforschung. 1997 Aug;47(8):968-74
9296286
Immunity. 2016 Apr 19;44(4):901-12
27096319
J Biol Chem. 2014 Dec 19;289(51):35246-63
25339175
PLoS One. 2011;6(9):e25060
21966414
Immunity. 2014 Apr 17;40(4):554-68
24726877
PLoS Pathog. 2005 Sep;1(1):e4
16201016
J Lab Clin Med. 1987 Nov;110(5):592-601
2444663
Antiviral Res. 2016 Feb;126:69-80
26738783
J Virol. 2016 Apr 14;90(9):4614-25
26912629
Free Radic Res. 2014 Aug;48(8):940-7
24869957
J Virol. 1990 Dec;64(12):6335-40
2243397
Biochem Biophys Res Commun. 2013 Oct 11;440(1):14-9
24012672
Nucleic Acids Res. 2016 Jan 4;44(D1):D457-62
26476454
Drugs Exp Clin Res. 1985;11(10):739-43
3836859
Equine Vet J. 1999 Mar;31(2):160-8
10213429
Dis Model Mech. 2014 Feb;7(2):205-13
24271778
Vaccine. 1997 Nov;15(16):1767-72
9364681
Virology. 2010 Jun 5;401(2):257-65
20334888
J Virol. 2008 Jul;82(14):6820-8
18448517
Phytomedicine. 2004 Nov;11(7-8):625-32
15636176
Antiviral Res. 2015 Aug;120:89-100
26022200
Am J Respir Cell Mol Biol. 2013 Jan;48(1):17-26
23002098
Respir Res. 2015 Mar 14;16:37
25849069
J Physiol Pharmacol. 2009 Dec;60 Suppl 7:67-70
20388947
Immunity. 2009 Apr 17;30(4):566-75
19362023
Lancet Infect Dis. 2016 Apr;16(4):e47-63
27036359
J Virol. 2012 Feb;86(3):1789-801
22114333
Int J Stroke. 2016 Jul;11(5):534-43
27048693
AIDS. 2010 Nov 27;24(18):2887-9
20962616
Nihon Ketsueki Gakkai Zasshi. 1989 Aug;52(5):906-15
2588949
PLoS Pathog. 2011 May;7(5):e1001340
21589892
Cell Biochem Funct. 2016 Jun;34(4):191-6
27001679
Oncogene. 2004 Aug 26;23(39):6639-46
15235583
Int J Immunopathol Pharmacol. 2000 Sep-Dec;13(3):123-128
12657201
Antimicrob Agents Chemother. 2014 Jul;58(7):3689-96
24752266
Inflammation. 2014 Dec;37(6):2091-8
24912813
J Interferon Cytokine Res. 2015 Jul;35(7):554-62
25756191
J Proteome Res. 2014 May 2;13(5):2223-38
24669782
Anticancer Drugs. 2009 Jun;20(5):346-54
19369827
Med Microbiol Immunol. 2016 Oct;205(5):501-9
27401907
PLoS One. 2011;6(6):e21444
21731751
J Autoimmun. 2016 Sep;73:42-53
27267461
J Virol. 2015 Dec 04;90(4):1812-23
26637453
Eur Respir J. 2002 May;19(5):952-8
12030738
Chirality. 2016 Jun;28(6):495-513
27225330
Assay Drug Dev Technol. 2015 Dec;13(10 ):638-49
26192013
J Clin Immunol. 2013 Feb;33(2):388-96
23064976
Biochim Biophys Acta. 2012 Feb;1820(2):90-5
22108550
J Clin Invest. 1990 Mar;85(3):739-45
2155924
Int J Exp Pathol. 2003 Jun;84(3):127-33
12974942
PLoS One. 2016 Jan 05;11(1):e0145629
26731261
Braz J Med Biol Res. 1997 Nov;30(11):1333-6
9532243
Traffic. 2003 May;4(5):333-43
12713661
J Nutr. 2006 Oct;136(10):2611-6
16988135
J Cell Biol. 1998 Mar 23;140(6):1357-67
9508769
Clin Exp Med. 2006 Jun;6(2):79-83
16820995
J Virol. 2010 Sep;84(18):9439-51
20592098
J Infect Dis. 2013 Dec 1;208(11):1898-905
23901080
J Allergy Clin Immunol. 2012 Oct;130(4):958-67.e14
23021143
Mol Pharmacol. 2013 Oct;84(4):615-29
23907213
Arch Virol. 1984;81(1-2):163-70
6743023
J Interferon Cytokine Res. 2009 Apr;29(4):199-207
19203244
Clin Rheumatol. 2013 Mar;32 Suppl 1:S21-3
20204666
PLoS One. 2011;6(6):e21756
21747924
Am J Physiol Lung Cell Mol Physiol. 2015 Dec 1;309(11):L1313-22
26432867
Zh Mikrobiol Epidemiol Immunobiol. 1985 Jun;(6):26-30
3898670
Proc Soc Exp Biol Med. 1976 May;152(1):67-70
177994
J Virol. 2013 Mar;87(6):3039-52
23283961
J Virol. 2009 Mar;83(6):2510-7
19129453
Expert Rev Anti Infect Ther. 2014 Nov;12(11):1325-36
25301229
J Mol Model. 2010 Mar;16(3):535-41
19669810
Small. 2014 Nov;10 (22):4746-53
24976105
Wei Sheng Wu Xue Bao. 2012 Sep 4;52(9):1137-42
23236848
Vopr Virusol. 1987 May-Jun;32(3):294-7
3314143
Virology. 2008 Aug 1;377(2):431-9
18570972
PLoS One. 2016 Apr 18;11(4):e0153674
27088501
Nat Methods. 2013 Dec;10(12):1209-10
24122041
Cell Microbiol. 2014 Dec;16(12):1854-74
25052580
PLoS One. 2013 Aug 30;8(8):e75005
24137500
Vet Microbiol. 2013 Mar 23;162(2-4):353-9
23123174
J Nat Med. 2016 Jul;70(3):571-83
26943796
J Nepal Health Res Counc. 2016 Jan;14 (32):69-70
27426715
PLoS One. 2014 Jan 31;9(1):e88062
24498245
Future Virol. 2012 Aug;7(8):801-818
23420457
Biochem Biophys Res Commun. 2016 Jan 22;469(4):848-55
26673392
Am J Addict. 2016 Aug;25(5):374-7
27288091
J Virol. 2011 Oct;85(19):10010-20
21795357
Appl Microbiol Biotechnol. 2014 Dec;98(23):9691-701
24903817
J Virol. 2011 Oct;85(19):10109-16
21752902
Expert Rev Neurother. 2015;15(11):1321-41
26513633
Curr Comput Aided Drug Des. 2013 Dec;9(4):547-55
24138396
PLoS One. 2012;7(11):e48335
23139774
Science. 2016 May 27;352(6289):aad7993
27127234
Nucleic Acids Res. 2014 Jan;42(Database issue):D1091-7
24203711
Vet Immunol Immunopathol. 2013 Nov 15;156(1-2):141-6
24126210
J Virol. 2012 Mar;86(6):3347-56
22238293
Sci Rep. 2016 Feb 24;6:22002
26906558
Eur J Neurol. 2013 Jun;20(6):975-80
23521577
J Exp Med. 2001 Jun 4;193(11):1319-26
11390439
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4440-5
27036003
J Virol. 2002 Oct;76(20):10455-64
12239322