Functional characterisation of selective vertebrate and invertebrate venoms on the modulation of human blood clotting and platelet function

Vijayakumar, P. (2026) Functional characterisation of selective vertebrate and invertebrate venoms on the modulation of human blood clotting and platelet function. PhD thesis, University of Reading. doi: 10.48683/1926.00130951

Abstract/Summary

Venom is a specialised biological fluid that has evolved over millions of years and consists of a rich variety of components, whose primary function is to act as a tool for predation or defence against predation. Venom has evolved in at least 100 lineages of animals, including snakes, scorpions, and spiders. Humans are accidental victims of venomous bites since they are not natural prey for any snake, scorpion, or spider. Snakebite envenoming (SBE) is a well known but neglected tropical disease that is estimated to annually cause over 150,000 fatalities globally. Scorpion stings and spider bites cause lower rates of death compared to SBE however the number of scorpion stings recorded annually can reach or surpass the number of SBE. Apart from medical significance, venoms from snakes, and increasingly from invertebrates such as scorpions and spiders, are being investigated for their potential applications in pharmaceutical drug development as well as other biotechnological applications such as agricultural bio-pesticides. The reason for this exploration is because venoms underwent natural selection for millions of years to become highly specific to select targets. Additionally, inherent features of many venom peptides, such as small size, high stability, and proteolytic resistance, offer unique templates for designing novel drug leads for the treatment of cardiovascular, neuromuscular, immunological, and oncological diseases. However, before these venoms can be explored for their therapeutic potential, their constituents have to be characterised. Despite strong reasons to explore venom for their therapeutic potential, only a few drugs developed from venom peptides are commercially available with regulatory approval such as captopril – an anti-hypertension drug, exenatide – an antidiabetic drug, ziconotide – an analgesic drug, eptifibatide and tirofiban – antiplatelet drugs. Venom-derived compounds have also achieved commercially successful use as a source for molecular tools in diagnostic assays that assess blood coagulation pathways such as Protac®, Reptilase® (Batroxobin), and Botrocetin®, among others. Many of these existing venom-derived drugs are based on a single type of venom component, proteases such as metalloproteases and serine proteases, and thus exhibit a common pathway or mechanism of action or target affinity. Since, venom is a diverse mix of components, other components with hypothetically novel therapeutic potential likely exist with different mechanisms of action and they remain functionally uncharacterised. Thus, this research study focuses on the characterisation of venoms for their ability to modulate coagulation and platelet function to establish novel functional characteristics. A multitude of in-vitro platelet function assays has been used to characterise potential platelet modulatory venom effects since platelets play a crucial role in coagulation and the functional information of venom effects against platelets is limited in literature in comparison to venom effects on coagulation. An example is Hemachatus haemachatus, an elapid snake whose anti coagulant effect is established but its effect on platelets is extremely limited and incomplete. Functional information about invertebrate venom effects, particularly scorpion and spider venoms since these are relatively easier to obtain compared to other invertebrates, on platelets or coagulation are also severely limited and the limited literature hypothesises novel peptides with unique mechanisms of action on blood coagulation pathways. In this study, venom from a single elapid snake, Hemachatus haemachatus, has been characterised to address the knowledge gap with respect to platelet modulation. Following the establishment of platelet modulatory properties, isolation and characterisation of responsible venom component has been achieved using chromatography and mass spectrometry techniques. Venom from hitherto uncharacterised species of scorpion and spider species have been functionally characterised to identify novel platelet and coagulation modulatory activities. The functional characterisation of these venoms has resulted in the establishment of significant platelet-inhibiting properties in Hemachatus haemachatus venom as well as the identification of the specific venom component responsible using mass spectrometry. Novel platelet modulatory properties have also been discovered in the scorpion and spider venoms investigated. Venom from two scorpion venoms, Paravaejovis confusus and Paravaejovis spinigerus displayed novel platelet inhibiting activity while the venom from two spider species, Cyrtopholis femoralis and Theraphosa stirmi, demonstrated a modulatory effect on platelet promoting procoagulant activity. This study establishes novel functional knowledge of uncharacterised venoms with future therapeutic potential for novel drug development.

Item Type	Thesis (PhD)
URI	https://centaur.reading.ac.uk/id/eprint/130951
Identification Number/DOI	10.48683/1926.00130951
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Chemistry, Food and Pharmacy
Date on Title Page	August 2025
Download/View statistics	View download statistics for this item