Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH19414
REVIEW
Contents Vol 73(4)

Natural Inhibitors of Snake Venom Metalloproteinases

Narumi Aoki-Shioi https://orcid.org/0000-0001-8326-6856 A B D , Cho Yeow Koh C and R. Manjunatha Kini B
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, Faculty of Science, Fukuoka University, 19-1, 8-chome Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

B Department of Biological Sciences, National University of Singapore, Singapore 117543, Republic of Singapore.

C Department of Medicine, Yong Loo Lin School of Medicine, 14 Medical Drive, MD6, Singapore 117599, Republic of Singapore.

D Corresponding author. Email: anarumi@fukuoka-u.ac.jp




Assistant Professor Narumi Aoki-Shioi works in the Department of Chemistry, Faculty of Science, Fukuoka University in Japan. Her research interest is new functional proteins and peptides from venomous snakes and their uses. Her research focuses on functional analysis of snake venom metalloprotease, discovery of endogenous inhibitors from venomous snakes, and analysis of their inhibitory mechanisms for development into therapeutics for snake envenomation. She has written 15 original research papers, four reviews, and one book chapter.


Dr Cho Yeow Koh is a Research Assistant Professor in the Department of Medicine, University of Singapore. He has strong interest in drug discovery and development research related to cardiovascular and neglected tropical diseases. He explores venomous and haematophagous animals for novel molecules that may be developed into therapeutics, medical technologies or research tools. Dr Koh has written 23 peer-reviewed scientific papers and two book chapters, and has eight patents in his name.


Professor R. Manjunatha Kini of the Department of Biological Sciences, National University of Singapore, is a leading authority on structure-function relationships of proteins from venomous animals, especially snakes. He has many years of experience in protein chemistry, biophysics, protein and peptide design and engineering. He has published more than 255 original research papers, reviews and book chapters. He also has 50 patent applications and started two small biotechnology companies. He is the President of the International Society of Toxinology, Vice President of the International Proteolysis Society, and the Editor-in-Chief of Toxin Reviews.

Australian Journal of Chemistry 73(4) 277-286 https://doi.org/10.1071/CH19414
Submitted: 21 September 2019  Accepted: 8 January 2020   Published: 5 March 2020

Abstract

Snakebites are a hazard in the tropical world. Although antivenom therapy is effective, it is beset with inherent drawbacks. A better understanding of the major components of snake venoms and their neutralisation will help in improving snakebite treatment. Snake venom metalloproteinases (SVMPs) are responsible for severe haemorrhage, the inhibition of coagulation and platelet aggregation, observed in the victims of snakebite envenoming. Inhibitors from various sources including medicinal plants, animal venoms, and sera are sought to block the pharmacological functions of SVMPs. In this review, we describe the interaction of natural inhibitors with SVMPs. To understand their inhibitory mechanisms, we focussed on the complex structures of these inhibitors and SVMPs. There are three distinct classes of inhibitors; namely, chelators, competitive inhibitors, and non-competitive inhibitors. A small number of inhibitors show their anti-hemorrhagic activity in in vivo animal models in treatment mode, but most studies evaluate either in vitro neutralisation of enzymatic activity or in vivo effects in pre-incubation protocols. We propose the distinct strategies and limitations to design either broad-spectrum or highly selective SVMP inhibitors. The goal of designing broad-spectrum inhibitors against SVMPs capable of effective treatment of snakebites without toxicity has been elusive, probably because of the narrow molecular footprint of inhibitors against a large number of SVMPs with distinct molecular surfaces. Our ability to design highly selective inhibitors is limited by the lack of information of interactions between selective inhibitors and SVMPs. Comparisons of structures of hemorrhagic and non-hemorrhagic SVMPs revealed different distributions of electric charge on the surface of SVMPs, which may be exploited to design specific inhibitors. The specific inhibitors may also be useful to identify target molecules of the SVMPs and help to understand their mechanism of action.


References

[1]  J. Maria Gutierrez, G. Leon, B. Lomonte, Y. Angulo, Inflamm. Allergy Drug Targets 2011, 10, 369.
         | Crossref | GoogleScholarGoogle Scholar |

[2]  R. Kini, S. Sidhu, A. Laustsen, Toxins 2018, 10, 534.
         | Crossref | GoogleScholarGoogle Scholar |

[3]  M. de Oliveira, W. L. G. Cavalcante, E. Z. Arruda, P. A. Melo, M. Dal-Pai Silva, M. Gallacci, Toxicon 2003, 42, 373.
         | Crossref | GoogleScholarGoogle Scholar | 14505937PubMed |

[4]  J.-M. Howes, R. D. G. Theakston, G. D. Laing, Toxicon 2007, 49, 734.
         | Crossref | GoogleScholarGoogle Scholar | 17196631PubMed |

[5]  K. Kulkeaw, Y. Sakolvaree, P. Srimanote, P. Tongtawe, S. Maneewatch, N. Sookrung, A. Tungtrongchitr, P. Tapchaisri, H. Kurazono, W. Chaicumpa, J. Proteomics 2009, 72, 270.
         | Crossref | GoogleScholarGoogle Scholar | 19162253PubMed |

[6]  G. Richard, A. J. Meyers, M. D. McLean, M. Arbabi-Ghahroudi, R. MacKenzie, J. C. Hall, PLoS ONE 2013, 8, e69495.
         | Crossref | GoogleScholarGoogle Scholar | 23922979PubMed |

[7]  A. H. Laustsen, A. Karatt-Vellatt, E. W. Masters, A. S. Arias, U. Pus, C. Knudsen, S. Oscoz, P. Slavny, D. T. Griffiths, A. M. Luther, R. A. Leah, M. Lindholm, B. Lomonte, J. M. Gutiérrez, J. McCafferty, Nat. Commun. 2018, 9, 3928.
         | Crossref | GoogleScholarGoogle Scholar | 30279409PubMed |

[8]  T. Tasoulis, G. Isbister, Toxins 2017, 9, 290.
         | Crossref | GoogleScholarGoogle Scholar |

[9]  C. Baldo, C. Jamora, N. Yamanouye, T. M. Zorn, A. M. Moura-da-Silva, PLoS Negl. Trop. Dis. 2010, 4, e727.
         | Crossref | GoogleScholarGoogle Scholar | 20614020PubMed |

[10]  J. M. Gutiérrez, J. J. Calvete, A. G. Habib, R. A. Harrison, D. J. Williams, D. A. Warrell, Nat. Rev. Dis. Primer 2017, 3, 17063.
         | Crossref | GoogleScholarGoogle Scholar |

[11]  T. Escalante, A. Rucavado, J. W. Fox, J. M. Gutiérrez, J. Proteomics 2011, 74, 1781.
         | Crossref | GoogleScholarGoogle Scholar | 21447411PubMed |

[12]  R. M. Kini, C. Y. Koh, Toxins 2016, 8, 284.
         | Crossref | GoogleScholarGoogle Scholar |

[13]  J. W. Fox, S. M. T. Serrano, FEBS J. 2008, 275, 3016.
         | Crossref | GoogleScholarGoogle Scholar | 18479462PubMed |

[14]  F. X. Gomis-Rüth, L. F. Kress, W. Bode, EMBO J. 1993, 12, 4151.
         | Crossref | GoogleScholarGoogle Scholar | 8223430PubMed |

[15]  S. Takeda, T. Igarashi, H. Mori, S. Araki, EMBO J. 2006, 25, 2388.
         | Crossref | GoogleScholarGoogle Scholar | 16688218PubMed |

[16]  G. V. Odell, P. C. Ferry, L. M. Vick, A. W. Fenton, L. S. Decker, R. L. Cowell, C. L. Ownby, J. M. Gutierrez, Toxicon 1998, 36, 1801.
         | Crossref | GoogleScholarGoogle Scholar | 9839664PubMed |

[17]  R. Marques-Porto, I. Lebrun, D. C. Pimenta, Comp. Biochem. Physiol. Part C: Toxicol. Pharmacol. 2008, 147, 424.
         | Crossref | GoogleScholarGoogle Scholar |

[18]  H.-H. Guan, K.-S. Goh, F. Davamani, P.-L. Wu, Y.-W. Huang, J. Jeyakanthan, W.-g. Wu, C.-J. Chen, J. Struct. Biol. 2010, 169, 294.
         | Crossref | GoogleScholarGoogle Scholar | 19932752PubMed |

[19]  A. Moura-da-Silva, M. Almeida, J. Portes-Junior, C. Nicolau, F. Gomes-Neto, R. Valente, Toxins 2016, 8, 183.
         | Crossref | GoogleScholarGoogle Scholar |

[20]  F. Grams, R. Huber, L. F. Kress, L. Moroder, W. Bode, FEBS Lett. 1993, 335, 76.
         | Crossref | GoogleScholarGoogle Scholar | 8243670PubMed |

[21]  C. A. Nicolau, P. C. Carvalho, I. L. M. Junqueira-de-Azevedo, A. Teixeira-Ferreira, M. Junqueira, J. Perales, A. G. C. Neves-Ferreira, R. H. Valente, J. Proteomics 2017, 151, 214.
         | Crossref | GoogleScholarGoogle Scholar | 27373870PubMed |

[22]  M. S. Luna, R. H. Valente, J. Perales, M. L. Vieira, N. Yamanouye, J. Proteomics 2013, 94, 460.
         | Crossref | GoogleScholarGoogle Scholar | 24176787PubMed |

[23]  R. H. Valente, P. R. Guimarães, M. Junqueira, A. G. C. Neves-Ferreira, M. R. Soares, A. Chapeaurouge, M. R. O. Trugilho, I. R. León, S. L. G. Rocha, A. L. Oliveira-Carvalho, L. S. Wermelinger, D. L. S. Dutra, L. I. Leão, I. L. M. Junqueira-de-Azevedo, P. L. Ho, R. B. Zingali, J. Perales, G. B. Domont, J. Proteomics 2009, 72, 241.
         | Crossref | GoogleScholarGoogle Scholar | 19211044PubMed |

[24]  T. Okamoto, T. Akuta, F. Tamura, A. van Der Vliet, T. Akaike, Biol. Chem. 2004, 385, 997.
         | Crossref | GoogleScholarGoogle Scholar | 15576319PubMed |

[25]  G. Murphy, H. Nagase, Mol. Aspects Med. 2008, 29, 290.
         | Crossref | GoogleScholarGoogle Scholar | 18619669PubMed |

[26]  I. Panfoli, D. Calzia, S. Ravera, A. Morelli, Toxins 2010, 2, 417.
         | Crossref | GoogleScholarGoogle Scholar | 22069593PubMed |

[27]  E. E. Sánchez, A. Rodríguez-Acosta, Immunopharmacol. Immunotoxicol. 2008, 30, 647.
         | Crossref | GoogleScholarGoogle Scholar | 18686104PubMed |

[28]  J. Félix-Silva, A. A. Silva-Junior, S. M. Zucolotto, M de F. Fernandes-Pedrosa, Evid. Based Complement. Alternat. Med. 2017, 2017, 1.
         | Crossref | GoogleScholarGoogle Scholar |

[29]  J. O. da Silva, J. S. Coppede, V. C. Fernandes, C. D. Sant’Ana, F. K. Ticli, M. V. Mazzi, J. R. Giglio, P. S. Pereira, A. M. Soares, S. V. Sampaio, J. Ethnopharmacol. 2005, 100, 145.
         | Crossref | GoogleScholarGoogle Scholar | 16054531PubMed |

[30]  L. H. F. Vale, M. M. Mendes, A. Hamaguchi, A. M. Soares, V. M. Rodrigues, M. I. Homsi-Brandeburgo, Basic Clin. Pharmacol. Toxicol. 2008, 103, 104.
         | Crossref | GoogleScholarGoogle Scholar |

[31]  L. F. M. Izidoro, V. M. Rodrigues, R. S. Rodrigues, E. V. Ferro, A. Hamaguchi, J. R. Giglio, M. I. Homsi-Brandeburgo, Biochimie 2003, 85, 669.
         | Crossref | GoogleScholarGoogle Scholar |

[32]  E. E. Sánchez, J. C. Lopez-Johnston, A. Rodríguez-Acosta, J. C. Pérez, Toxicon 2008, 51, 297.
         | Crossref | GoogleScholarGoogle Scholar | 18054059PubMed |

[33]  V. Bastos, F. Gomes-Neto, J. Perales, A. Neves-Ferreira, R. Valente, Toxins 2016, 8, 250.
         | Crossref | GoogleScholarGoogle Scholar |

[34]  K.-F. Huang, C.-C. Hung, S.-H. Wu, S.-H. Chiou, Biochem. Biophys. Res. Commun. 1998, 248, 562.
         | Crossref | GoogleScholarGoogle Scholar | 9703966PubMed |

[35]  K.-F. Huang, S.-H. Chiou, T.-P. Ko, A. H.-J. Wang, Eur. J. Biochem. 2002, 269, 3047.
         | Crossref | GoogleScholarGoogle Scholar | 12071970PubMed |

[36]  B. Francis, I. I. Kaiser, Toxicon 1993, 31, 889.
         | Crossref | GoogleScholarGoogle Scholar | 8212033PubMed |

[37]  S. C. Wagstaff, P. Favreau, O. Cheneval, G. D. Laing, M. C. Wilkinson, R. L. Miller, R. Stöcklin, R. A. Harrison, Biochem. Biophys. Res. Commun. 2008, 365, 650.
         | Crossref | GoogleScholarGoogle Scholar | 18029259PubMed |

[38]  S. M. Munekiyo, S. P. Mackessy, Toxicon 2005, 45, 255.
         | Crossref | GoogleScholarGoogle Scholar | 15683863PubMed |

[39]  P. Favreau, O. Cheneval, L. Menin, S. Michalet, H. Gaertner, F. Principaud, R. Thai, A. Ménez, P. Bulet, R. Stöcklin, Rapid Commun. Mass Spectrom. 2007, 21, 406.
         | Crossref | GoogleScholarGoogle Scholar | 17206746PubMed |

[40]  J. Perales, A. G. C. Neves-Ferreira, R. H. Valente, G. B. Domont, Toxicon 2005, 45, 1013.
         | Crossref | GoogleScholarGoogle Scholar | 15922772PubMed |

[41]  A. G. C. Neves-Ferreira, J. Perales, J. W. Fox, J. D. Shannon, D. L. Makino, R. C. Garratt, G. B. Domont, J. Biol. Chem. 2002, 277, 13129.
         | Crossref | GoogleScholarGoogle Scholar |

[42]  L. Preciado, J. Comer, V. Núñez, P. Rey-Súarez, J. Pereañez, Molecules 2018, 23, 2662.
         | Crossref | GoogleScholarGoogle Scholar |

[43]  V. Srinivasa, M. S. Sundaram, S. Anusha, M. Hemshekhar, S. C. Nayaka, K. Kemparaju, Basappa, K. S. Girish, K. S. Rangappa, PLoS ONE 2014, 9, e106364.
         | Crossref | GoogleScholarGoogle Scholar | 25184206PubMed |

[44]  P. T. Baraldi, A. J. Magro, F. F. Matioli, S. Marcussi, N. Lemke, L. A. Calderon, R. G. Stábeli, A. M. Soares, A. G. Correa, M. R. M. Fontes, Biochimie 2016, 121, 179.
         | Crossref | GoogleScholarGoogle Scholar | 26700145PubMed |

[45]  M. Choudhury, V. Senthilvadivel, D. Velmurugan, J. Biochem. Mol. Toxicol. 2018, 32, e22224.
         | Crossref | GoogleScholarGoogle Scholar | 30276921PubMed |

[46]  M. M. Mendes, S. A. P. B. Vieira, M. S. R. Gomes, V. F. Paula, T. M. Alcântara, M. I. Homsi-Brandeburgo, J. I. dos Santos, A. J. Magro, M. R. M. Fontes, V. M. Rodrigues, Phytochemistry 2013, 86, 72.
         | Crossref | GoogleScholarGoogle Scholar | 23141056PubMed |

[47]  T.-L. Chou, C.-H. Wu, K.-F. Huang, A. H.-J. Wang, Toxicon 2013, 71, 140.
         | Crossref | GoogleScholarGoogle Scholar | 23732127PubMed |

[48]  A. S. Arias, A. Rucavado, J. M. Gutiérrez, Toxicon 2017, 132, 40.
         | Crossref | GoogleScholarGoogle Scholar | 28400263PubMed |

[49]  Y. Yamakawa, T. Omori-Satoh, J. Biochem. 1992, 112, 583.
         | Crossref | GoogleScholarGoogle Scholar | 1478916PubMed |

[50]  M. Deshimaru, C. Tanaka, K. Fujino, N. Aoki, S. Terada, S. Hattori, M. Ohno, Toxicon 2005, 46, 937.
         | Crossref | GoogleScholarGoogle Scholar | 16289179PubMed |

[51]  N. Aoki, A. Sakiyama, M. Deshimaru, S. Terada, Biochem. Biophys. Res. Commun. 2007, 359, 330.
         | Crossref | GoogleScholarGoogle Scholar | 17543280PubMed |

[52]  N. Aoki, H. Matsuo, M. Deshimaru, S. Terada, Gene 2008, 426, 7.
         | Crossref | GoogleScholarGoogle Scholar | 18817856PubMed |

[53]  N. Shioi, E. Ogawa, Y. Mizukami, S. Abe, R. Hayashi, S. Terada, J. Biochem. 2013, 153, 121.
         | Crossref | GoogleScholarGoogle Scholar | 23100271PubMed |

[54]  N. Shioi, A. Nishijima, S. Terada, J. Biochem. 2015, 158, 37.
         | Crossref | GoogleScholarGoogle Scholar | 25681613PubMed |

[55]  A. G. C. Neves-Ferreira, N. Cardinale, S. L. G. Rocha, J. Perales, G. B. Domont, Biochim. Biophys. Acta BBA – Gen. Subj. 2000, 1474, 309.
         | Crossref | GoogleScholarGoogle Scholar |

[56]  S. Ainsworth, J. Slagboom, N. Alomran, D. Pla, Y. Alhamdi, S. I. King, F. M. S. Bolton, J. M. Gutiérrez, F. J. Vonk, C.-H. Toh, J. J. Calvete, J. Kool, R. A. Harrison, N. R. Casewell, Commun. Biol. 2018, 1, 34.
         | Crossref | GoogleScholarGoogle Scholar | 30271920PubMed |

[57]  R. A. de Souza, N. Díaz, R. A. P. Nagem, R. S. Ferreira, D. Suárez, J. Comput. Aided Mol. Des. 2016, 30, 69.
         | Crossref | GoogleScholarGoogle Scholar | 26676823PubMed |

[58]  R. Doley, S. Pahari, S. P. Mackessy, R. M. Kini, BMC Evol. Biol. 2008, 8, 196.
         | Crossref | GoogleScholarGoogle Scholar | 18606022PubMed |

[59]  R. Doley, S. P. Mackessy, R. M. Kini, BMC Evol. Biol. 2009, 9, 146.
         | Crossref | GoogleScholarGoogle Scholar | 19563684PubMed |

[60]  M. Lewin, L. Gilliam, J. Gilliam, S. Samuel, T. Bulfone, P. Bickler, J. Gutiérrez, Toxins 2018, 10, 479.
         | Crossref | GoogleScholarGoogle Scholar |

[61]  C. Knudsen, A. Laustsen, Trop. Med. Infect. Dis. 2018, 3, 42.
         | Crossref | GoogleScholarGoogle Scholar |

[62]  W. Gong, X. Zhu, S. Liu, M. Teng, L. Niu, J. Mol. Biol. 1998, 283, 657.
         | Crossref | GoogleScholarGoogle Scholar | 9784374PubMed |

[63]  X. Zhu, M. Teng, L. Niu, Acta Crystallogr. D Biol. Crystallogr. 1999, 55, 1834.
         | Crossref | GoogleScholarGoogle Scholar | 10531480PubMed |

[64]  L. Watanabe, J. D. Shannon, R. H. Valente, A. Rucavado, A. Alape-Girón, A. S. Kamiguti, R. D. G. Theakston, J. W. Fox, J. M. Gutiérrez, R. K. Arni, Protein Sci. 2003, 12, 2273.
         | Crossref | GoogleScholarGoogle Scholar | 14500885PubMed |

[65]  T. Lingott, C. Schleberger, J. M. Gutiérrez, I. Merfort, Biochemistry 2009, 48, 6166.
         | Crossref | GoogleScholarGoogle Scholar | 19485419PubMed |

[66]  P. K. Akao, C. C. C. Tonoli, M. S. Navarro, A. C. O. Cintra, J. R. Neto, R. K. Arni, M. T. Murakami, Toxicon 2010, 55, 361.
         | Crossref | GoogleScholarGoogle Scholar | 19706302PubMed |

[67]  R. N. Ferreira, B. Rates, M. Richardson, B. G. Guimarães, E. O. F. Sanchez, A. M. C. Pimenta, R. A. P. Nagem, Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2009, 65, 798.
         | Crossref | GoogleScholarGoogle Scholar | 19652343PubMed |

[68]  M. Cirilli, C. Gallina, E. Gavuzzo, C. Giordano, F. X. Gomis-Rüth, B. Gorini, L. F. Kress, F. Mazza, M. Paglialunga Paradisi, G. Pochetti, V. Politi, FEBS Lett. 1997, 418, 319.
         | Crossref | GoogleScholarGoogle Scholar | 9428736PubMed |

[69]  F. X. Gomis-Rüth, E. F. Meyer, L. F. Kress, V. Politi, Protein Sci. 1998, 7, 283.
         | Crossref | GoogleScholarGoogle Scholar | 9521103PubMed |

[70]  K.-F. Huang, S.-H. Chiou, T.-P. Ko, J.-M. Yuann, A. H.-J. Wang, Acta Crystallogr. D Biol. Crystallogr. 2002, 58, 1118.
         | Crossref | GoogleScholarGoogle Scholar | 12077431PubMed |

[71]  T. Kumasaka, M. Yamamoto, H. Moriyama, N. Tanaka, M. Sato, Y. Katsube, Y. Yamakawa, T. Omori-Satoh, S. Iwanaga, T. Ueki, J. Biochem. 1996, 119, 49.
         | Crossref | GoogleScholarGoogle Scholar | 8907175PubMed |

[72]  Z. Zhu, Y. Gao, Z. Zhu, Y. Yu, X. Zhang, J. Zang, M. Teng, L. Niu, Biochem. Biophys. Res. Commun. 2009, 386, 159.
         | Crossref | GoogleScholarGoogle Scholar | 19505434PubMed |

[73]  J. R. C. Muniz, A. L. B. Ambrosio, H. S. Selistre-de-Araujo, M. R. Cominetti, A. M. Moura-da-Silva, G. Oliva, R. C. Garratt, D. H. F. Souza, Toxicon 2008, 52, 807.
         | Crossref | GoogleScholarGoogle Scholar |

[74]  S. Takeda, T. Igarashi, H. Mori, FEBS Lett. 2007, 581, 5859.
         | Crossref | GoogleScholarGoogle Scholar | 18060879PubMed |

[75]  H. T. Aung, T. Nikai, Y. Komori, T. Nonogaki, M. Niwa, Y. Takaya, Toxins 2010, 2, 2478.
         | Crossref | GoogleScholarGoogle Scholar | 22069562PubMed |