Venom Pathophysiology

BIOLAB | Resintox Peptide Intelligence
Clinical Brief

Venom Pathophysiology

The common European adder (Vipera berus berus) presents a critical biochemical challenge. Venom profiles are highly dynamic; substantial variations in proteomic composition occur not only across geographic ranges but also between melanistic (black) and normally coloured phenotypes and area where they live.

Hemostatic Disruption

Primary toxicity is driven by Phospholipase A2 (PLA2). Enzymes like Daboxin P homologs act as potent anticoagulants by binding to Factor X/Xa, disrupting the coagulation cascade. Simultaneously, svPLA2s induce intense local inflammation and nociception through mechanisms that are both catalytic-dependent and independent.

“Snake blood serum contains endogenous PLA2 inhibitors (PLIs), believed to protect against autointoxication. Alpha-type PLIs and acidic modulators like HPD-11 serve as the foundation for our synthetic neutralization strategies.”

Target Profile: P31854

Classification Basic Asp49
Amino Acids 122 AA
Molecular Mass 13,853 Da
Structure Group IIA

Scientific Goal

Develop a chemically defined, non-immunogenic peptide framework to replace traditional polyclonal serotherapy.

Molecular Designer

Structure-based design for active site blockade.

Hydrophobic Core

Catalytic Warheads

Stabilisers

Therapeutic Design Buffer
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Sequence Analyzer Standby

Initialise peptide construction by selecting amino acids. A therapeutic sequence for the P31854 group IIA PLA2 requires hydrophobic anchors and a specific warhead residue.

Molecular Docking

The structural rationale for active-site inhibition.

Hydrophobic Anchor

Group IIA PLA2 enzymes feature a narrow hydrophobic channel. Synthetic inhibitors must contain a core of Leucine, Isoleucine, or Alanine to anchor within this cleft via van der Waals forces.

Precedent: LAIYS / 1JQ8

Catalytic Warhead

The warhead (e.g., Tyrosine or Arginine) replicates the interaction of the substrate. Tyr forms H-bonds with the His48/Asp49 catalytic dyad, effectively disabling the enzyme’s hydrolytic capacity.

Mechanism: Salt Bridge / 1MF4

Interfacial Binding Shield

Active-site Blocker

Directly targets the active site channel to prevent the cleavage of the sn-2 fatty acyl bond in phospholipids.

Membrane Shield

Designed to be complementary to the interfacial binding surface (i-face), physically preventing the toxin from docking onto cell surfaces.

Point-of-Care Framework

The RAPID System

A conceptual leap toward the Rapid on-site analyte-specific peptide intervention and diversion system for snakebite management.

Field Analysis

Diagnostic sensors identify specific toxin isoforms at the bite site to determine the required peptide profile.

Rapid Synthesis

Microwave-Assisted SPPS technology allows for automated production of personalised therapeutics on-demand.

Logistical Ease

Synthetic, chemically stable peptides eliminate the cold-chain logistical hurdles that hinder traditional antivenom distribution.

Global Health Equity

This framework shifts the paradigm from broad-spectrum biologicals to high-precision synthetic molecules, ensuring rapid emergency care across all geographic boundaries.