Venom has been used throughout history to treat illness and there has been a significant amount of research in recent times into the potential applications of synthetic venoms to treat a variety of ailments. For example, ziconotide from cone snails to treat chronic pain or lepirudin from leeches to prevent blood clots.

A more drastic shift in the protocol to assess venom LD 50 and antivenom ED 50 uses a maximum observation period of 8h [see, for example, Barber et al. ( 107)]. In this methodology, envenomed animals are observed at regular time intervals, e.g., every hour, and the severity of envenoming is graded according to a pre-established set of parameters. Animals that are severely affected at any time interval, i.e., are moribund, are euthanized, and all animals surviving at the end of the 8-h observation period are also euthanized. This modification of the classical methodology reduces the extent of animal suffering, although it may affect the precision of the results, as it has been observed that mice that appear moribund may then recover. A balance needs to be made between the need to refine the lethality test and the need to ensure the robustness of the test for assessing antivenom efficacy. This urges the development of studies to assess the correlation between the results of these improved protocols and those of classical protocols. Concluding RemarksEven though antivenomics is not a functional test in terms of neutralization of venom activities, it can shed valuable information for understanding the preclinical efficacy of antivenoms. The relative weight of venom components in the overall toxicity of a venom can be studied by determining the ‘toxicity score’ for each component, which takes into consideration the toxicity of each toxin and its relative abundance in the venom ( 24). Once the most relevant toxins in a venom are identified, the ability of antivenoms to recognize these components can be quantified through antivenomics, hence providing indirect evidence of efficacy of the antivenom. The centerpiece in the therapy of snakebite envenomings is the timely administration of safe and effective antivenoms, which are preparations of IgGs or IgG fragments prepared from the plasma of horses or other animals immunized with venoms of one snake species (monospecific antivenoms) or several species (polyspecific antivenoms) ( 5). Upon parenteral administration in envenomed patients, antivenom antibodies bind to venom components in the circulation or in tissue compartments and contribute to their elimination. Generally, antivenom therapy is complemented by ancillary treatments which vary depending on the pathophysiology of envenomings ( 1). Antivenom efficacy is evaluated at the preclinical level by assessing its capacity to neutralize the lethal action of venoms in animal models, usually mice ( 5, 6). This is the gold standard of antivenom efficacy which is required before antivenoms are introduced into clinical use and as part of the routine quality control of antivenoms by manufacturers and regulatory agencies. The basic protocol for these neutralization assays involves the incubation of venom and antivenom prior to administration in animals. Another experimental option, which is not routinely used in quality control laboratories but which better mimics the actual circumstances of a snake bite, is the rescue-type assay, in which venom is injected first and antivenom is administered afterwards. In addition to lethality, depending on the toxicity profile of venoms, the assessment of neutralization of other toxic activities is also recommended, such as hemorrhagic, myotoxic, dermonecrotic, defibrinogenating, and in vitro coagulant activities, depending on the venom ( 5, 6). Except for the in vitro coagulant activity, the rest of these assays involve the use of high numbers of mice, with the consequent suffering and distress inflicted in these animals because of the toxic action of venoms.

Schumanniophyton magnificum, Aristolochia radix, Diospyros kaki, Alocasia cucullata, Picrasma quassioides, Eclipta prostrata, Curcuma sp., Soja hispida, Diodia scandens, Andrographis paniculata Also, scientists have demonstrated the anti-ophidian properties of Anacardium occidentale bark extract. The study published in the journal Immunopharmacology and Immunotoxicology demonstrated the ability of Anacardium occidentale bark extract to neutralise enzymatic as well as pharmacological effects induced by Vipera russelii venom. The term “natural products” spans an extremely large and diverse range of chemical compounds derived and isolated from biological sources such as plants, minerals, and organic matter. Interest in natural products that have been used for over a thousand years is continuing based on the experience of randomized trials and animal observations. In ancient times, people acquired knowledge on plant use to treat diseases. For example, Chinese herbal medicine (CHM) and Indian herbal medicine (Ayurvedic) were highly developed in antiquity. China, Japan, Korea, and India still influence modern healthcare [ 32]. In recent years, natural products have experienced a resurgence in drug discovery programs, mainly due to their superior chemical diversity over synthetic compound libraries and their drug-like properties. There are several widely used drugs derived from natural sources, which are available in the form of food supplements, nutraceuticals, and complementary and alternative medicines. In fact, some widely used drugs used to treat certain life-threatening diseases are derived from natural sources, such as paclitaxel and artemisinin, which are used as anticancer and antimalarial agents, respectively [ 38]. Scientists have also demonstrated the inhibition of snake venom enzymes and anti-venom adjuvant effects of Azadirachta indica leaf extracts. Mouriri pusa (Melastomataceae), Byrsonima crassa (Malpighiaceae), and Davilla elliptica (Dilleniaceae)

Concluding Remarks

A solution to this situation is the identification and isolation of venom components having the highest toxicity in a venom, by assessing the ‘toxicity score’ of venom fractions ( 24). Once these toxins are identified, ELISAs can be developed for the quantification of antibodies against them. This increases the likelihood of correlation between immunoassays and the in vivo neutralization of lethality. This concept has been proven in the case of antivenom against Naja naja siamensis, since a higher correlation was observed when immunoassays were carried out using a purified α-neurotoxin, as compared to crude venom ( 17). Similarly, a higher correlation was described for the Brazilian bothropic antivenom when using a hemorrhagic fraction of the venom of B. jararaca as compared to crude venom, but not when using a phospholipase A 2 (PLA 2)-rich fraction ( 21, 25). The growing body of information of snake venom proteomes, together with the identification of key toxins, provides valuable evidence for the setting of these more directed ELISAs. Administration of the methanolic extracts from Vitis vinifera (Vitaceae) resulted in the reduction of local symptoms produced by D. russelli venom due to the inhibition of the proteolytic and hyaluronidase activities reducing edema, myonecrosis, and hemorrhaging. Keep an eye on:There is a potential hazard for the peptide to travel through the body and have off-target effects on other muscle groups in the body, potentially causing generalized muscle weakness. How Is Venom Used in Medicine? Coagulopathy, i.e. defibrinogenation, is a common consequence of envenomings by viperids and some elapids and ‘colubrids’ and contributes to the systemic hemorrhage characteristic of these envenomings ( 1, 31, 53). Defibrinogenating effect is tested in vivo by determining the minimum dose of venom that renders blood unclottable in experimental animals ( 54, 55). Defibrinogenation is the consequence of the consumption of clotting factors owing to the action of procoagulant enzymes in venoms, i.e., factor X activators, prothrombin activators and thrombin-like enzymes ( 31, 56). Therefore, the in vitro coagulant activity of venoms is likely to be a surrogate test for in vivo defibrinogenating effect. Indeed, a relationship was shown between the ability of a polyspecific antivenom to neutralize in vitro coagulant and in vivo defibrinogenating activities of five viperid venoms ( 55).