Beyond the 'big four': Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
23
08
2019
accepted:
01
11
2019
entrez:
6
12
2019
pubmed:
6
12
2019
medline:
26
2
2020
Statut:
epublish
Résumé
Snakebite in India causes the highest annual rates of death (46,000) and disability (140,000) than any other country. Antivenom is the mainstay treatment of snakebite, whose manufacturing protocols, in essence, have remained unchanged for over a century. In India, a polyvalent antivenom is produced for the treatment of envenomations from the so called 'big four' snakes: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis carinatus). In addition to the 'big four', India is abode to many other species of venomous snakes that have the potential to inflict severe clinical or, even, lethal envenomations in their human bite victims. Unfortunately, specific antivenoms are not produced against these species and, instead, the 'big four' antivenom is routinely used for the treatment. We characterized the venom compositions, biochemical and pharmacological activities and toxicity profiles (mouse model) of the major neglected yet medically important Indian snakes (E. c. sochureki, B. sindanus, B. fasciatus, and two populations of N. kaouthia) and their closest 'big four' congeners. By performing WHO recommended in vitro and in vivo preclinical assays, we evaluated the efficiencies of the commercially marketed Indian antivenoms in recognizing venoms and neutralizing envenomations by these neglected species. As a consequence of dissimilar ecologies and diet, the medically important snakes investigated exhibited dramatic inter- and intraspecific differences in their venom profiles. Currently marketed antivenoms were found to exhibit poor dose efficacy and venom recognition potential against the 'neglected many'. Premium Serums antivenom failed to neutralise bites from many of the neglected species and one of the 'big four' snakes (North Indian population of B. caeruleus). This study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the 'neglected many'.
Sections du résumé
BACKGROUND
Snakebite in India causes the highest annual rates of death (46,000) and disability (140,000) than any other country. Antivenom is the mainstay treatment of snakebite, whose manufacturing protocols, in essence, have remained unchanged for over a century. In India, a polyvalent antivenom is produced for the treatment of envenomations from the so called 'big four' snakes: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis carinatus). In addition to the 'big four', India is abode to many other species of venomous snakes that have the potential to inflict severe clinical or, even, lethal envenomations in their human bite victims. Unfortunately, specific antivenoms are not produced against these species and, instead, the 'big four' antivenom is routinely used for the treatment.
METHODS
We characterized the venom compositions, biochemical and pharmacological activities and toxicity profiles (mouse model) of the major neglected yet medically important Indian snakes (E. c. sochureki, B. sindanus, B. fasciatus, and two populations of N. kaouthia) and their closest 'big four' congeners. By performing WHO recommended in vitro and in vivo preclinical assays, we evaluated the efficiencies of the commercially marketed Indian antivenoms in recognizing venoms and neutralizing envenomations by these neglected species.
FINDINGS
As a consequence of dissimilar ecologies and diet, the medically important snakes investigated exhibited dramatic inter- and intraspecific differences in their venom profiles. Currently marketed antivenoms were found to exhibit poor dose efficacy and venom recognition potential against the 'neglected many'. Premium Serums antivenom failed to neutralise bites from many of the neglected species and one of the 'big four' snakes (North Indian population of B. caeruleus).
CONCLUSIONS
This study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the 'neglected many'.
Identifiants
pubmed: 31805055
doi: 10.1371/journal.pntd.0007899
pii: PNTD-D-19-01352
pmc: PMC6894822
doi:
Substances chimiques
Antitoxins
0
Antivenins
0
Snake Venoms
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0007899Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Toxicol Lett. 2017 Oct 5;280:159-170
pubmed: 28847519
Naunyn Schmiedebergs Arch Pharmacol. 1972;272(4):402-16
pubmed: 4260261
Interdiscip Toxicol. 2013 Sep;6(3):136-40
pubmed: 24678250
J Proteomics. 2019 Feb 20;193:243-254
pubmed: 30385415
Evolution. 2002 Oct;56(10):2067-82
pubmed: 12449493
Toxicon. 2015 Nov;106:97-107
pubmed: 26415904
PLoS Negl Trop Dis. 2017 Oct 18;11(10):e0005969
pubmed: 29045429
Biochim Biophys Acta. 1965 Jun 1;98(3):554-65
pubmed: 5891200
Toxins (Basel). 2017 Mar 13;9(3):
pubmed: 28335411
J Thromb Haemost. 2005 Aug;3(8):1791-9
pubmed: 16102046
Annu Rev Genomics Hum Genet. 2009;10:483-511
pubmed: 19640225
Biochim Biophys Acta. 2000 Mar 7;1477(1-2):146-56
pubmed: 10708855
J Biol Chem. 2004 Jul 16;279(29):30836-43
pubmed: 15131128
Toxicon. 2011 Jun;57(7-8):1073-80
pubmed: 21549143
Eur J Biochem. 1980 Dec;112(3):493-9
pubmed: 7460933
Nat Commun. 2018 Jun 13;9(1):2304
pubmed: 29899337
J Venom Anim Toxins Incl Trop Dis. 2014 Jun 02;20:23
pubmed: 24940304
Toxicon. 2006 Sep 15;48(4):411-21
pubmed: 16899266
Proteome Sci. 2006 May 11;4:11
pubmed: 16689994
Toxins (Basel). 2013 Nov 18;5(11):2172-208
pubmed: 24253238
Anal Biochem. 1976 May 7;72:248-54
pubmed: 942051
Curr Med Chem. 2018;25(21):2520-2530
pubmed: 29119915
Toxins (Basel). 2018 Dec 04;10(12):
pubmed: 30518149
Toxicon. 2005 Jun 15;45(8):951-67
pubmed: 15922768
Toxicon. 2019 Jun;164:31-43
pubmed: 30953661
Int J Biol Macromol. 2018 Jan;106:193-199
pubmed: 28782616
J Biol Chem. 1956 May;220(1):303-6
pubmed: 13319348
Ecol Lett. 2019 Mar;22(3):527-537
pubmed: 30616302
Anal Biochem. 1981 Dec;118(2):262-8
pubmed: 7337224
Comp Biochem Physiol C Toxicol Pharmacol. 2008 Jan;147(1):85-95
pubmed: 17904425
Comp Biochem Physiol C Toxicol Pharmacol. 2001 Mar;128(3):425-56
pubmed: 11255115
PLoS Negl Trop Dis. 2017 Nov 27;11(11):e0006068
pubmed: 29176824
Proc Biol Sci. 2009 Jul 7;276(1666):2443-9
pubmed: 19364745
PLoS Negl Trop Dis. 2009 Dec 22;3(12):e569
pubmed: 20027216
Biochemistry (Mosc). 2010 Jan;75(1):1-6
pubmed: 20331418
Thromb Haemost. 1982 Dec 27;48(3):277-82
pubmed: 7164017
Biochimie. 2004 Mar;86(3):193-202
pubmed: 15134834
Toxicon. 2011 Mar 15;57(4):586-99
pubmed: 21223975
Toxicon. 2006 Mar;47(3):304-12
pubmed: 16373076
Toxicon. 1999 Mar;37(3):411-45
pubmed: 10080349
Methods Mol Biol. 1984;1:41-55
pubmed: 20512673
J Gen Appl Microbiol. 2009 Aug;55(4):291-4
pubmed: 19700923
Biologicals. 2013 Mar;41(2):93-7
pubmed: 23190453
J Proteomics. 2013 Aug 26;89:15-23
pubmed: 23714137
PLoS Negl Trop Dis. 2010 Oct 26;4(10):e851
pubmed: 21049058
Biochimie. 2004 Mar;86(3):203-10
pubmed: 15134835
Toxicon. 2013 Mar 1;63:19-31
pubmed: 23159397
Cell Biochem Funct. 2010 Apr;28(3):171-7
pubmed: 20186872
Trends Ecol Evol. 2013 Apr;28(4):219-29
pubmed: 23219381
Toxicon. 2016 Sep 1;119:280-8
pubmed: 27377229
Toxicon. 2003 Dec 15;42(8):827-40
pubmed: 15019485
J Proteomics. 2014 Mar 17;99:68-83
pubmed: 24463169
Toxicon. 2005 Jun 15;45(8):1115-32
pubmed: 15922778
Thromb Res. 1988 Dec 15;52(6):541-52
pubmed: 3232124
Toxicon. 2011 Nov;58(6-7):558-64
pubmed: 21924279
Apoptosis. 2006 Aug;11(8):1439-51
pubmed: 16770529
PLoS Negl Trop Dis. 2011 Apr 12;5(4):e1018
pubmed: 21532748
Toxicon. 1983;21(4):491-501
pubmed: 6312633
Toxicol Lett. 2018 Apr;286:39-47
pubmed: 29197624
Cell Biochem Funct. 2006 Jan-Feb;24(1):7-12
pubmed: 16245359
Toxicon. 1991;29(11):1279-303
pubmed: 1814005
Toxicon. 2011 May;57(6):841-50
pubmed: 21356226
J Proteomics. 2009 Mar 6;72(2):165-82
pubmed: 19344652
J Proteomics. 2014 Jun 13;105:323-39
pubmed: 24576642
Biomed Res Int. 2017;2017:6592820
pubmed: 29318152
Biochim Biophys Acta Gen Subj. 2017 Apr;1861(4):814-823
pubmed: 28130154
J Venom Res. 2013 Nov 06;4:31-8
pubmed: 24349704
Mol Biol Evol. 2012 Jul;29(7):1807-22
pubmed: 22319140
Toxins (Basel). 2017 Sep 18;9(9):
pubmed: 28927001
World J Biol Chem. 2019 Jan 7;10(1):17-27
pubmed: 30622682
Anal Biochem. 2001 Nov 1;298(1):136-9
pubmed: 11673909
Toxicol In Vitro. 2019 Oct;60:330-335
pubmed: 31170449
Toxins (Basel). 2016 Mar 26;8(4):86
pubmed: 27023606
Toxicon. 1986;24(11-12):1099-106
pubmed: 3031852
Infect Immun. 1990 Dec;58(12):4159-62
pubmed: 2254038
Toxicon. 2013 Feb;62:19-26
pubmed: 23010164
Curr Pharm Des. 2007;13(28):2872-86
pubmed: 17979732
J Proteomics. 2017 Jul 5;164:1-18
pubmed: 28476572
Toxicon. 2013 Feb;62:3-18
pubmed: 23000249
Saudi Med J. 2015 May;36(5):634-7
pubmed: 25935188
Expert Rev Proteomics. 2019 May;16(5):457-469
pubmed: 31002271
J Proteome Res. 2008 Aug;7(8):3556-71
pubmed: 18557640
Sci Rep. 2017 Dec 7;7(1):17119
pubmed: 29215036
J Proteomics. 2013 Jul 11;87:103-21
pubmed: 23727490
Toxicon. 1985;23(5):777-82
pubmed: 4089873
Nat Commun. 2016 Apr 19;7:11361
pubmed: 27093631