Venom Can Be Used As Future Therapeutic Agents Against Cancer, TB, And HIV/AIDS

Venom is a secretion produced by specific animals, which is synthesized in the specialized cells of their body. Animal venoms constitute a plethora of bioactive molecules with high affinity for diversified targets in cells.

Despite their tremendous toxicity, animals’ venoms can be used to investigate physiological mechanisms and represent auspicious components for drug development. As a matter of fact, the bioactive components of venoms have been investigated as a colossal source of important therapeutic agents. Interestingly, tremendous variation and molecular diversity of distinct groups of venoms have opened up whole new avenues for future therapeutic microbiology. 

According to the recent Global Cancer Statistics, there are approximately 32.6 million cancer patients globally, representing it as one of the primary causes of mortality in the world. Among discrete anticancer agents in targeted therapies, animal venoms have created tremendous interest when designing new effectual anticancer drugs. Venoms extracted from snakes of families Viperidae, Elapidae, Atractaspididae, and Colubridae are known to exhibit an anticancer trait. Venoms of these families contain Bradykinin-potentiating peptides, L-amino acid oxidases, Cysteine-rich secretory proteins, Phospholipase A2, Phosphodiesterases, Acetylcholinesterases, Metalloproteinases, Three-finger toxins, Arginine esterases, C-type lectins, Disintegrins, Myotoxins, Hyaluronidases, Serine proteases, Sarafotoxins, and Prothrombin activators.

Wasp venoms showed anticancer activity against diverse cell lines with a varied mode of actions. Polybia MP1 isolated from Polybia paulista showed anticancer activity against prostate and bladder cancer cells through diversified modes of actions such as depolarization, irreversible cytolysis, inhibition of tumor cell proliferation, and membrane disruption. Quinone isolated from Vespa simillima exhibited anticancer activity against rat liver cancer cells by inducing apoptosis. NVP (1) isolated from Nidus vespae revealed anticancer traits against HepG2 cells by condensing nuclear chromatin, arresting cell cycle at G1 phase, and inhibiting mRNA expression.

Venoms extracted from toads (Bufo gargarizans, B. melanostictus, and Rana ridibunda), centipede (Parafontaria laminate), caterpillar (Hyalophora cecropia), and ants (Solenopsis invicta) showed anticancer attribute against distinct cancer cell lines viz. HeLa, human bladder carcinoma, human leukemia, colon carcinoma, breast adenocarcinoma, lung carcinoma, melanoma, and angiosarcoma.

Likewise, diverse scorpion species such as Buthus martensii Karsch (BmK), Heterometrus bengalensis Koch, Androctonus amoreuxi, Odontobuthus doriae, Tityus discrepans, Androctonus crassicauda, Androctonus bicolour, Leiurus quinquestriatus, Buthus tumulus, Tityus serrulatus are known to exhibit anticancer activity against various cancer cell lines by up-regulating caspase 3, arresting cell cycle, inducing membrane blabbing, inducing DNA fragmentation, inducing mitochondria depolarization, arresting cell cycle on S-phase, decreasing cell motility, blocking K⁺ channels, and affecting Na⁺ channels. Cantharidin, a monoterpene derived from Mylabris phalerata and M. cichorii (Chinese blister beetles) exhibited in vitro anticancer property against human leukemic cells. Bioactive components viz. melittin, apamin, adolapin, mast-cell-degranulating peptide, PA2, histamine, and epinephrine of bee venom are known to target various cancer cells. Lycosin-1 (from Lycosa singoriensis venom) showed growth inhibition of varied cancer cells like fibrosarcoma, lung adenocarcinoma, prostate carcinoma, colon adenocarcinoma, cervix carcinoma, and hepatocellular carcinoma. Macrothele raveni spider associated venom also suppressed the growth of human myelogenous leukemia cells. 

Tuberculosis (TB) is one of the deadliest tropical diseases which causes millions of deaths by infecting human macrophages. According to the latest data from the World Health Organization, about 10.4 million new TB cases were reported worldwide. Venoms extracted from Naja naja, Bungarus fasciatus, Daboia russelli russelli, and Naja kaouthia showed anti-tubercular property against drug-resistant TB. An antimicrobial peptide isolated from Pandinus imperator (scorpion) venom also showed promising antimycobacterial activity.

Currently, about 36.7 million people were reported to be infected with the human immunodeficiency virus (HIV) globally. Snake venoms showed virucidal property against multidrug-resistant HIV by reducing virus count and elevating T CD⁴⁺. Trimeresurus stejnegeri venom associated TSV-LAO was the first snake venom LAO to depict antiviral trait by inhibiting the formation of syncytium and HIV-1 p24 antigen expression. Phospholipases A2 exhibited anti-HIV activity by blocking viral entry into the host cells. Phospholipases A2 NmmCMIII from Naja mossambica, taipoxin from Oxyuranus scutellatus, and nigexine from Naja nigricollis also revealed antiviral trait against HIV. Metalloprotease inhibitors extracted from snake venoms showed anti-HIV activity by preventing the new HIV particles production and by inhibiting the viral proteases.

Modified peptides viz. caerin 1.1, caerin 1.9, and maculatin 1.1 isolated from the skin of the amphibians Litoria caerulea, L. Chloris, and L. genimaculata, respectively, exhibited anti-HIV activity by disintegrating the viral envelope, preventing the virus’ attachment to the cell membrane and obstructing the viral transfection from dendritic cells to T cells. Bee venom associated PA2 showed anti-HIV property by blocking M and T-tropic HIV virions replication. Melittin (an amphipathic peptide), isolated from Apis mellifera venom was conjugated with nanoparticles and showed anti-HIV activity in the epithelial vaginal cell line (VK2) and TZM-bl reporter cells. Synthetic hybrid peptide, particularly cecropin A (1-8)-magainin 2 (1-12) from silk moth (Hyalophora cecropia) showed promising antiviral properties by blocking the fusion of a virus with host cells. The cyclic depsipeptides mirabamides A-H, isolated from Siliquaria spongia mirabilis and Stelletta clavosa exhibited antiviral property by blocking the entry of HIV-1 into TZM-bl cells. Homophymine A (a cyclodepsipeptide) isolated from Homophymia sp. also showed in vitro anti-HIV-1 activity at lower concentrations.

Various peptides and depsipeptides such as koshikamides F and H (from T. swinhoei and T. cupola), papuamides A and B (from Theonella sp.), and theopapuamide A (from T. swinhoei) exhibited anti-HIV activity by inhibiting the entry of the virus into T cells. Sponges associated other anti-HIV-1 peptides were also observed, namely callipeltin A from the genus Callipelta, celebesides A-C from S. spongia mirabilis, neamphamide A from Neamphius huxleyi, and microspinosamide from Sidonops microspinosa. Marine arthropods associated tachyplesin and polyphemusin (T140) peptides exhibited antiviral activity by showing attachment to CXCR4. In a nutshell, in the future, venom-based drug development might create a new therapeutic era, getting rid of uncontrolled epidemics of cancer, TB, and HIV/AIDS. 

These findings are described in the article entitled Venom as therapeutic weapon to combat dreadful diseases of 21st century: A systematic review on cancer, TB, and HIV/AIDS, recently published in the journal Microbial Pathogenesis. This work was conducted by Ameer Khusro and Chirom Aarti from Loyola College, Alberto Barbabosa-Pliego from the Universidad Autónoma del Estado de México, Raymundo Rene Rivas-Cáceres from the Universidad Autónoma de Ciudad Juárez, and Moisés Cipriano-Salazar from the Universidad Autónoma de Gurrero.