Targeting Key Enzymatic Snake Venom Proteins Using Repurposed Small Molecule Inhibitors: Emerging Adjuncts to...

Area of Science:

• Toxicology
• Pharmacology
• Tropical Medicine

Background:

• Snakebite envenoming is a major global health issue causing significant mortality and disability.
• Current antivenoms have limitations in efficacy due to venom variation and poor toxin neutralization.
• Alternative treatments targeting key venom proteins are being explored.

Purpose of the Study:

• To review the potential of small molecule inhibitors as adjuncts to antivenom therapy for snakebite envenoming.
• To focus on inhibitors targeting phospholipase A2, snake venom metalloproteinases, and serine proteases.
• To highlight the advantages of small molecules, such as safety and oral bioavailability.

Main Methods:

• Literature review of preclinical and in vitro studies on small molecule inhibitors.
• Analysis of studies investigating inhibitors against specific snake venom enzyme families.
• Compilation of data on the efficacy of small molecules alone or in combination with antivenom.

Main Results:

• Small molecule inhibitors demonstrate potential in reducing venom-induced coagulopathy, neurotoxicity, tissue damage, and inflammation.
• Repurposed drugs offer safety, oral bioavailability, and lower costs compared to traditional antivenoms.
• In vitro studies show promise for targeting key enzymatic snake venom proteins.

Conclusions:

• Small molecules are mechanistically targeted and promising adjuncts to antivenom therapy.
• Gaps remain, including limited human clinical trial data and undefined dosing strategies.
• Further validation through randomized trials and pharmacokinetic studies is warranted for field applicability.