Mechanisms of the action of povidone-iodine against human and avian influenza A viruses: its effects on hemagglutination and sialidase activities.
BACKGROUND
Influenza virus infection causes significant morbidity and mortality and has marked social and economic impacts throughout the world. The influenza surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), act cooperatively to support efficient influenza A virus replication and provide the most important targets for anti-influenza chemotherapy. In this study, povidone-iodine (PVP-I), which has a broad-spectrum microbicidal property, was examined for its inhibitory effects against influenza virus infection in MDCK cells and the mechanisms of PVP-I action on HA and NA were revealed.


RESULTS
Results obtained using a novel fluorescence- and chromogenic-based plaque inhibition assay showed that 1.56 mg/ml PVP-I inhibited infections in MDCK cells of human (8 strains) and avian (5 strains) influenza A viruses, including H1N1, H3N2, H5N3 and H9N2, from 23.0-97.5%. A sialidase inhibition assay revealed that PVP-I inhibited N1, N2 and N3 neuraminidases with IC50 values of 9.5-212.1 microg/ml by a mixed-type inhibition mechanism. Receptor binding inhibition and hemagglutinin inhibition assays indicated that PVP-I affected viral hemagglutinin rather than host-specific sialic acid receptors.


CONCLUSIONS
Mechanisms of reduction of viral growth in MDCK cells by PVP-I involve blockade of viral attachment to cellular receptors and inhibition of viral release and spread from infected cells. Therefore, PVP-I is useful to prevent infection and limit spread of human and avian influenza viruses.
Sriwilaijaroen
Nongluk
N
Faculty of Medicine, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand. snongluk@hotmail.com
Wilairat
Prapon
P
Hiramatsu
Hiroaki
H
Takahashi
Tadanobu
T
Suzuki
Takashi
T
Ito
Morihiro
M
Ito
Yasuhiko
Y
Tashiro
Masato
M
Suzuki
Yasuo
Y
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001717:Birds; D002460:Cell Line; D002642:Chick Embryo; D006168:Guinea Pigs; D006384:Hemagglutination / Q000187:drug effects; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D005585:Influenza in Birds / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D007251:Influenza, Human / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011206:Povidone-Iodine / Q000494:pharmacology*
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011206:Povidone-Iodine; D009439:Neuraminidase
Biol Pharm Bull. 2009 Jul;32(7):1188-92
19571383
Arch Pharm (Weinheim). 1999 May;332(5):151-7
10409102
Med J Aust. 2006 Nov 20;185(S10):S39-43
17115950
Dermatology. 2006;212 Suppl 1:115-8
16490988
Rev Med Virol. 2003 Mar-Apr;13(2):85-97
12627392
Biochem J. 1996 Sep 1;318 ( Pt 2):389-93
8809024
Virology. 1996 Mar 15;217(2):452-8
8610436
J Am Chem Soc. 2007 Oct 3;129(39):11892-3
17850083
Virology. 2008 Apr 25;374(1):198-209
18234269
Nature. 2006 Nov 16;444(7117):378-82
17108965
Nature. 2008 Jun 26;453(7199):1258-61
18480754
Antimicrob Agents Chemother. 2005 Nov;49(11):4515-20
16251290
J Virol. 2008 Jun;82(12):5940-50
18417587
Antimicrob Agents Chemother. 2001 Oct;45(10):2723-32
11557461
J Acquir Immune Defic Syndr (1988). 1989;2(1):16-20
2465403
J Virol. 2005 Mar;79(5):2814-22
15709000
Antiviral Res. 2002 May;54(2):89-97
12062394
Nature. 1993 Jun 3;363(6428):418-23
8502295
J Antimicrob Chemother. 2007 Jun;59(6):1114-22
17439975
Lancet. 1985 Oct 26;2(8461):949-50
2865446
Postgrad Med J. 1993;69 Suppl 3:S78-83
8290463
Nature. 2006 Mar 23;440(7083):435-6
16554799
Glycoconj J. 1998 Nov;15(11):1099-108
10386895
Emerg Infect Dis. 2007 Sep;13(9):1354-7
18252107
Carbohydr Res. 1998 Sep;311(1-2):51-9
9821266
Dermatology. 1997;195 Suppl 2:29-35
9403252
Acta Chir Belg. 2003 Jun;103(3):241-7
12914356
Antimicrob Agents Chemother. 1998 Mar;42(3):647-53
9517946
Apoptosis. 2005 Jan;10(1):201-8
15711936
J Int Med Res. 1977;5(5):378-81
913866
Bioorg Med Chem Lett. 2002 Aug 5;12(15):1921-4
12113809
Int Wound J. 2007 Jun;4(2):124-37
17651228
Nat Rev Drug Discov. 2007 Dec;6(12):967-74
18049471
J Virol. 2000 Jul;74(13):6015-20
10846083
Am J Surg. 1986 Mar;151(3):400-6
3513654
Biol Pharm Bull. 2005 Mar;28(3):399-408
15744059
Glycobiology. 2002 Mar;12(3):183-90
11971862
J Virol Methods. 1984 Dec;9(4):271-6
6099370
Nature. 2005 Oct 20;437(7062):1108
16228009