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70. Walker, C.S.; Jensen, S.; Ellison, M.; Matta, J.A.; Lee, W.Y.; Imperial, J.S.; Duclos, N.; Brockie, P.J.; Madsen, D.M.; Isaac, J.T.R.; et al. A Novel Conus Snail Polypeptide Causes Excitotoxicity by Blocking Desensitization of AMPA Receptors. *Curr. Biol.* **2009**, *19*, 900–908. [CrossRef]

71. Möller, C.; Clark, E.; Safavi-Hemami, H.; DeCaprio, A.; Marí, F. Isolation and Characterization of Conohyal-P1, a Hyaluronidase from the Injected Venom of *Conus purpurascens*. *J. Proteom.* **2017**, *164*, 73–84. [CrossRef] [PubMed]

72. Möller, C.; Davis, W.C.; Clark, E.; DeCaprio, A.; Marí, F. Conodipine-P1-3, the First Phospholipases A2 Characterized from Injected Cone Snail Venom. *Mol. Cell. Proteom.* **MCP** **2019**, *18*, 876–891. [CrossRef] [PubMed]

73. Möller, C.; Vanderweit, N.; Bubis, J.; Marí, F. Comparative Analysis of Proteases in the Injected and Dissected Venom of Cone Snail Species. *Toxicon* **2013**, *65*, 59–67. [CrossRef]

74. Safavi-Hemami, H.; Möller, C.; Marí, F.; Purcell, A.W. High Molecular Weight Components of the Injected Venom of Fish-Hunting Cone Snails Target the Vascular System. *J. Proteom.* **2013**, *91*, 97–105. [CrossRef]

75. Nicke, A.; Loughnan, M.L.; Millard, E.L.; Alewood, P.F.; Adams, D.J.; Daly, N.L.; Craik, D.J.; Lewis, R.J. Isolation, Structure, and Activity of GID, a Novel A4/7-Conotoxin with an Extended N-Terminal Sequence. *J. Biol. Chem.* **2003**, *278*, 3137–3144. [CrossRef] [PubMed]

76. England, L.J.; Imperial, J.; Jacobsen, R.; Craig, A.G.; Gulyas, J.; Akhtar, M.; Rivier, J.; Julius, D.; Olivera, B.M. Inactivation of a Serotonin-Gated Ion Channel by a Polypeptide Toxin from Marine Snails. *Science* **1998**, *281*, 575–578. [CrossRef]

77. Diversity of Conus Neuropeptides. Available online: https://www.science.org/doi/10.1126/science.2165278 (accessed on 14 December 2023).

78. Jakubowski, J.A.; Sweedler, J.V. Sequencing and Mass Profiling Highly Modified Conotoxins Using Global Reduction/Alkylation Followed by Mass Spectrometry. *Anal. Chem.* **2004**, *76*, 6541–6547. [CrossRef] [PubMed]

79. Jakubowski, J.A.; Kelley, W.P.; Sweedler, J.V. Screening for Post-Translational Modifications in Conotoxins Using Liquid Chromatography/Mass Spectrometry: An Important Component of Conotoxin Discovery. *Toxicon* **2006**, *47*, 688–699. [CrossRef] [PubMed]

80. Abalde, S.; Dutertre, S.; Zardoya, R. A Combined Transcriptomics and Proteomics Approach Reveals the Differences in the Predatory and Defensive Venoms of the Molluscivorous Cone Snail *Cylinder ammiralis* (*Caenogastropoda*: Conidae). *Toxins* **2021**, *13*, 642. [CrossRef] [PubMed]
56. Himaya, S.; Lewis, R. Venomics-Accelerated Cone Snail Venom Peptide Discovery. *Int. J. Mol. Sci.* **2018**, *19*, 788. [CrossRef] [PubMed]

57. Yanagawa, Y.; Abe, T.; Satake, M.; Odani, S.; Suzuki, J.; Ishikawa, K. A Novel Sodium Channel Inhibitor from *Conus geographus*: Purification, Structure, and Pharmacological Properties. *Biochemistry* **1988**, *27*, 6256–6262. [CrossRef] [PubMed]

58. Del Río-Sancho, S.; Cros, C.; Coutaz, B.; Cuendet, M.; Kalia, Y.N. Cutaneous Iontophoresis of μ-Conotoxin CnIIIC-A Potent NaV1.4 Antagonist with Analgesic, Anaesthetic and Myorelaxant Properties. *Int. J. Pharm.* **2017**, *518*, 59–65. [CrossRef]

59. Zhang, M.-M.; Fiedler, B.; Green, B.R.; Catlin, P.; Watkins, M.; Garrett, J.E.; Smith, B.J.; Yoshikami, D.; Olivera, B.M.; Bulaj, G. Structural and Functional Diversities among μ-Conotoxins Targeting TTX-Resistant Sodium Channels. *Biochemistry* **2006**, *45*, 3723–3732. [CrossRef]

60. Olivera, B.M.; McIntosh, J.M.; Curz, L.J.; Luque, F.A.; Gray, W.R. Purification and Sequence of a Presynaptic Peptide Toxin from *Conus geographus* Venom. *Biochemistry* **1984**, *23*, 5087–5090. [CrossRef]

61. Lewis, R.J.; Nielsen, K.J.; Craik, D.J.; Loughnan, M.L.; Adams, D.A.; Sharpe, I.A.; Luchian, T.; Adams, D.J.; Bond, T.; Thomas, L.; et al. Novel ω-Conotoxins from *Conus Catus* Discriminate among Neuronal Calcium Channel Subtypes. *J. Biol. Chem.* **2000**, *275*, 35335–35344. [CrossRef] [PubMed]

62. Zhou, K.; Luo, W.; Liu, T.; Ni, Y.; Qin, Z. Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications. *Toxins* **2023**, *15*, 18. [CrossRef]

63. Safavi-Hemami, H.; Brogan, S.E.; Olivera, B.M. Pain Therapeutics from Cone Snail Venoms: From Ziconotide to Novel Non-Opioid Pathways. *J. Proteom.* **2019**, *190*, 12–20. [CrossRef]

64. Zafaralla, G.C.; Ramilo, C.; Gray, W.R.; Karlstrom, R.; Olivera, B.M.; Cruz, L.J. Phylogenetic Specificity of Cholinergic Ligands: Alpha.-Conotoxin SI. *Biochemistry* **1988**, *27*, 7102–7105. [CrossRef]

65. Dutertre, S.; Croker, D.; Daly, N.L.; Andersson, Å.; Muttenthaler, M.; Lumsden, N.G.; Craik, D.J.; Alewood, P.F.; Guillon, G.; Lewis, R.J. Conopressin-T from *Conus tulipa* Reveals an Antagonist Switch in Vasopressin-like Peptides. *J. Biol. Chem.* **2008**, *283*, 7100–7108. [CrossRef]

66. Haack, J.A.; Rivier, J.; Parks, T.N.; Mena, E.E.; Cruz, L.J.; Olivera, B.M. Conantokin-T. A Gamma-Carboxyglutamate Containing Peptide with N-Methyl-d-Aspartate Antagonist Activity. *J. Biol. Chem.* **1990**, *265*, 6025–6029. [CrossRef]

67. Craig, A.G.; Norberg, T.; Griffin, D.; Hoeger, C.; Akhtar, M.; Schmidt, K.; Low, W.; Dykert, J.; Richelson, E.; Navarro, V.; et al. Contulakin-G, an O-Glycosylated Invertebrate Neurotensin. *J. Biol. Chem.* **1999**, *274*, 13752–13759. [CrossRef] [PubMed]

68. Bayrhuber, M.; Vijayan, V.; Ferber, M.; Graf, R.; Korukottu, J.; Imperial, J.; Garrett, J.E.; Olivera, B.M.; Terlau, H.; Zweckstetter, M.; et al. Conkunitzin-S1 Is the First Member of a New Kunitz-Type Neurotoxin Family. *J. Biol. Chem.* **2005**, *280*, 23766–23770. [CrossRef] [PubMed]

69. Möller, C.; Marí, F. 9.3 KDa Components of the Injected Venom of *Conus purpurascens* Define a New Five-Disulfide Conotoxin Framework. *Pept. Sci.* **2011**, *96*, 158–165. [CrossRef] [PubMed]

70. Walker, C.S.; Jensen, S.; Ellison, M.; Matta, J.A.; Lee, W.Y.; Imperial, J.S.; Duclos, N.; Brockie, P.J.; Madsen, D.M.; Isaac, J.T.R.; et al. A Novel Conus Snail Polypeptide Causes Excitotoxicity by Blocking Desensitization of AMPA Receptors. *Curr. Biol.* **2009**, *19*, 900–908. [CrossRef]

71. Möller, C.; Clark, E.; Safavi-Hemami, H.; DeCaprio, A.; Marí, F. Isolation and Characterization of Conohyal-P1, a Hyaluronidase from the Injected Venom of *Conus purpurascens*. *J. Proteom.* **2017**, *164*, 73–84. [CrossRef] [PubMed]

72. Möller, C.; Davis, W.C.; Clark, E.; DeCaprio, A.; Marí, F. Conodipine-P1-3, the First Phospholipases A2 Characterized from Injected Cone Snail Venom. *Mol. Cell. Proteom.* **MCP** **2019**, *18*, 876–891. [CrossRef] [PubMed]

73. Möller, C.; Vanderweit, N.; Bubis, J.; Marí, F. Comparative Analysis of Proteases in the Injected and Dissected Venom of Cone Snail Species. *Toxicon* **2013**, *65*, 59–67. [CrossRef]

74. Safavi-Hemami, H.; Möller, C.; Marí, F.; Purcell, A.W. High Molecular Weight Components of the Injected Venom of Fish-Hunting Cone Snails Target the Vascular System. *J. Proteom.* **2013**, *91*, 97–105. [CrossRef]

75. Nicke, A.; Loughnan, M.L.; Millard, E.L.; Alewood, P.F.; Adams, D.J.; Daly, N.L.; Craik, D.J.; Lewis, R.J. Isolation, Structure, and Activity of GID, a Novel A4/7-Conotoxin with an Extended N-Terminal Sequence. *J. Biol. Chem.* **2003**, *278*, 3137–3144. [CrossRef] [PubMed]

76. England, L.J.; Imperial, J.; Jacobsen, R.; Craig, A.G.; Gulyas, J.; Akhtar, M.; Rivier, J.; Julius, D.; Olivera, B.M. Inactivation of a Serotonin-Gated Ion Channel by a Polypeptide Toxin from Marine Snails. *Science* **1998**, *281*, 575–578. [CrossRef]

77. Diversity of Conus Neuropeptides. Available online: https://www.science.org/doi/10.1126/science.2165278 (accessed on 14 December 2023).

78. Jakubowski, J.A.; Sweedler, J.V. Sequencing and Mass Profiling Highly Modified Conotoxins Using Global Reduction/Alkylation Followed by Mass Spectrometry. *Anal. Chem.* **2004**, *76*, 6541–6547. [CrossRef] [PubMed]

79. Jakubowski, J.A.; Kelley, W.P.; Sweedler, J.V. Screening for Post-Translational Modifications in Conotoxins Using Liquid Chromatography/Mass Spectrometry: An Important Component of Conotoxin Discovery. *Toxicon* **2006**, *47*, 688–699. [CrossRef] [PubMed]

80. Abalde, S.; Dutertre, S.; Zardoya, R. A Combined Transcriptomics and Proteomics Approach Reveals the Differences in the Predatory and Defensive Venoms of the Molluscivorous Cone Snail *Cylinder ammiralis* (*Caenogastropoda*: Conidae). *Toxins* **2021**, *13*, 642. [CrossRef] [PubMed]
81. Dutertre, S.; Jin, A.; Kaas, Q.; Jones, A.; Alewood, P.F.; Lewis, R.J. Deep Venomics Reveals the Mechanism for Expanded Peptide Diversity in Cone Snail Venom. *Mol. Cell. Proteom.* **2013**, *12*, 312–329. [CrossRef] [PubMed]

82. Corpuz, G.P.; Jacobsen, R.B.; Jimenez, E.C.; Watkins, M.; Walker, C.; Colledge, C.; Garrett, J.E.; McDougal, O.; Li, W.; Gray, W.R.; et al. Definition of the M-Conotoxin Superfamily: Characterization of Novel Peptides from Molluscivorous *Conus* Venoms. *Biochemistry* **2005**, *44*, 8176–8186. [CrossRef] [PubMed]

83. Wang, Y.; Shao, X.; Li, M.; Wang, S.; Chi, C.; Wang, C. Mr1e, a Conotoxin from *Conus Marmoreus* with a Novel Disulfide Pattern. *Acta Biochim. Biophys. Sin.* **2008**, *40*, 391–396. [CrossRef]

84. McIntosh, J.M.; Hasson, A.; Spira, M.E.; Gray, W.R.; Li, W.; Marsh, M.; Hillyard, D.R.; Olivera, B.M. A New Family of Conotoxins That Blocks Voltage-Gated Sodium Channels. *J. Biol. Chem.* **1995**, *270*, 16796–16802. [CrossRef]

85. Grant, M.A.; Hansson, K.; Furie, B.C.; Furie, B.; Stenflo, J.; Rigby, A.C. The Metal-Free and Calcium-Bound Structures of a γ-Carboxyglutamic Acid-Containing Contryphan from Conus Marmoreus, Glacontryphan-M. *J. Biol. Chem.* **2004**, *279*, 32464–32473. [CrossRef]

86. Prashanth, J.R.; Dutertre, S.; Jin, A.H.; Lavergne, V.; Hamilton, B.; Cardoso, F.C.; Griffin, J.; Venter, D.J.; Alewood, P.F.; Lewis, R.J. The Role of Defensive Ecological Interactions in the Evolution of Conotoxins. *Mol. Ecol.* **2016**, *25*, 598–615. [CrossRef]

87. Jin, A.-H.; Vetter, I.; Himaya, S.W.A.; Alewood, P.F.; Lewis, R.J.; Dutertre, S. Transcriptome and Proteome of Conus Planorbis Identify the Nicotinic Receptors as Primary Target for the Defensive Venom. *Proteomics* **2015**, *15*, 4030–4040. [CrossRef]

88. Casewell, N.R.; Jackson, T.N.W.; Laustsen, A.H.; Sunagar, K. Causes and Consequences of Snake Venom Variation. *Trends Pharmacol. Sci.* **2020**, *41*, 570–581. [CrossRef] [PubMed]

89. Rogalski, A.; Himaya, S.W.A.; Lewis, R.J. Coordinated Adaptations Define the Ontogenetic Shift from Worm- to Fish-Hunting in a Venomous Cone Snail. *Nat. Commun.* **2023**, *14*, 3287. [CrossRef] [PubMed]

90. Prunier, G.; Cherkaoui, M.; Lysiak, A.; Langella, O.; Blein-Nicolas, M.; Lollier, V.; Benoist, E.; Jean, G.; Fertin, G.; Rogniaux, H.; et al. Fast Alignment of Mass Spectra in Large Proteomics Datasets, Capturing Dissimilarities Arising from Multiple Complex Modifications of Peptides. *BMC Bioinform.* **2023**, *24*, 421. [CrossRef] [PubMed]

91. Prashanth, J.R.; Dutertre, S.; Rai, S.K.; Lewis, R.J. Venomics Reveals a Non-Compartmentalised Venom Gland in the Early Diverged Vermivorous Conus Distans. *Toxins* **2022**, *14*, 226. [CrossRef] [PubMed]

92. Lin, Z.; Torres, J.P.; Watkins, M.; Paguigan, N.; Niu, C.; Imperial, J.S.; Tun, J.; Safavi-Hemami, H.; Finol-Urdaneta, R.K.; Neves, J.L.B.; et al. Non-Peptidic Small Molecule Components from Cone Snail Venoms. *Front. Pharmacol.* **2021**, *12*, 655981. [CrossRef] [PubMed]

93. Neves, J.L.B.; Lin, Z.; Imperial, J.S.; Antunes, A.; Vasconcelos, V.; Olivera, B.M.; Schmidt, E.W. Small Molecules in the Cone Snail Arsenal. *Org. Lett.* **2015**, *17*, 4933–4935. [CrossRef] [PubMed]

94. Torres, J.P.; Lin, Z.; Watkins, M.; Salcedo, P.F.; Baskin, R.P.; Elhabian, S.; Safavi-Hemami, H.; Taylor, D.; Tun, J.; Concepcion, G.P.; et al. Small-Molecule Mimicry Hunting Strategy in the Imperial Cone Snail, *Conus imperialis*. *Sci. Adv.* **2021**, *7*, eabf2704. [CrossRef] [PubMed]

95. Walker, A.A.; Robinson, S.D.; Hamilton, B.F.; Undheim, E.A.B.; King, G.F. Deadly Proteomes: A Practical Guide to Proteotranscriptomics of Animal Venoms. *Proteomics* **2020**, *20*, 1900324. [CrossRef] [PubMed]

**Disclaimer/Publisher's Note:** The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
81. Dutertre, S.; Jin, A.; Kaas, Q.; Jones, A.; Alewood, P.F.; Lewis, R.J. Deep Venomics Reveals the Mechanism for Expanded Peptide Diversity in Cone Snail Venom. *Mol. Cell. Proteom.* **2013**, *12*, 312–329. [CrossRef] [PubMed]

82. Corpuz, G.P.; Jacobsen, R.B.; Jimenez, E.C.; Watkins, M.; Walker, C.; Colledge, C.; Garrett, J.E.; McDougal, O.; Li, W.; Gray, W.R.; et al. Definition of the M-Conotoxin Superfamily: Characterization of Novel Peptides from Molluscivorous *Conus* Venoms. *Biochemistry* **2005**, *44*, 8176–8186. [CrossRef] [PubMed]

83. Wang, Y.; Shao, X.; Li, M.; Wang, S.; Chi, C.; Wang, C. Mr1e, a Conotoxin from *Conus Marmoreus* with a Novel Disulfide Pattern. *Acta Biochim. Biophys. Sin.* **2008**, *40*, 391–396. [CrossRef]

84. McIntosh, J.M.; Hasson, A.; Spira, M.E.; Gray, W.R.; Li, W.; Marsh, M.; Hillyard, D.R.; Olivera, B.M. A New Family of Conotoxins That Blocks Voltage-Gated Sodium Channels. *J. Biol. Chem.* **1995**, *270*, 16796–16802. [CrossRef]

85. Grant, M.A.; Hansson, K.; Furie, B.C.; Furie, B.; Stenflo, J.; Rigby, A.C. The Metal-Free and Calcium-Bound Structures of a γ-Carboxyglutamic Acid-Containing Contryphan from Conus Marmoreus, Glacontryphan-M. *J. Biol. Chem.* **2004**, *279*, 32464–32473. [CrossRef]

86. Prashanth, J.R.; Dutertre, S.; Jin, A.H.; Lavergne, V.; Hamilton, B.; Cardoso, F.C.; Griffin, J.; Venter, D.J.; Alewood, P.F.; Lewis, R.J. The Role of Defensive Ecological Interactions in the Evolution of Conotoxins. *Mol. Ecol.* **2016**, *25*, 598–615. [CrossRef]

87. Jin, A.-H.; Vetter, I.; Himaya, S.W.A.; Alewood, P.F.; Lewis, R.J.; Dutertre, S. Transcriptome and Proteome of Conus Planorbis Identify the Nicotinic Receptors as Primary Target for the Defensive Venom. *Proteomics* **2015**, *15*, 4030–4040. [CrossRef]

88. Casewell, N.R.; Jackson, T.N.W.; Laustsen, A.H.; Sunagar, K. Causes and Consequences of Snake Venom Variation. *Trends Pharmacol. Sci.* **2020**, *41*, 570–581. [CrossRef] [PubMed]

89. Rogalski, A.; Himaya, S.W.A.; Lewis, R.J. Coordinated Adaptations Define the Ontogenetic Shift from Worm- to Fish-Hunting in a Venomous Cone Snail. *Nat. Commun.* **2023**, *14*, 3287. [CrossRef] [PubMed]

90. Prunier, G.; Cherkaoui, M.; Lysiak, A.; Langella, O.; Blein-Nicolas, M.; Lollier, V.; Benoist, E.; Jean, G.; Fertin, G.; Rogniaux, H.; et al. Fast Alignment of Mass Spectra in Large Proteomics Datasets, Capturing Dissimilarities Arising from Multiple Complex Modifications of Peptides. *BMC Bioinform.* **2023**, *24*, 421. [CrossRef] [PubMed]

91. Prashanth, J.R.; Dutertre, S.; Rai, S.K.; Lewis, R.J. Venomics Reveals a Non-Compartmentalised Venom Gland in the Early Diverged Vermivorous Conus Distans. *Toxins* **2022**, *14*, 226. [CrossRef] [PubMed]

92. Lin, Z.; Torres, J.P.; Watkins, M.; Paguigan, N.; Niu, C.; Imperial, J.S.; Tun, J.; Safavi-Hemami, H.; Finol-Urdaneta, R.K.; Neves, J.L.B.; et al. Non-Peptidic Small Molecule Components from Cone Snail Venoms. *Front. Pharmacol.* **2021**, *12*, 655981. [CrossRef] [PubMed]

93. Neves, J.L.B.; Lin, Z.; Imperial, J.S.; Antunes, A.; Vasconcelos, V.; Olivera, B.M.; Schmidt, E.W. Small Molecules in the Cone Snail Arsenal. *Org. Lett.* **2015**, *17*, 4933–4935. [CrossRef] [PubMed]

94. Torres, J.P.; Lin, Z.; Watkins, M.; Salcedo, P.F.; Baskin, R.P.; Elhabian, S.; Safavi-Hemami, H.; Taylor, D.; Tun, J.; Concepcion, G.P.; et al. Small-Molecule Mimicry Hunting Strategy in the Imperial Cone Snail, *Conus imperialis*. *Sci. Adv.* **2021**, *7*, eabf2704. [CrossRef] [PubMed]

95. Walker, A.A.; Robinson, S.D.; Hamilton, B.F.; Undheim, E.A.B.; King, G.F. Deadly Proteomes: A Practical Guide to Proteotranscriptomics of Animal Venoms. *Proteomics* **2020**, *20*, 1900324. [CrossRef] [PubMed]

**Disclaimer/Publisher's Note:** The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.