A Review of the Proteomic Profiling of African Viperidae and Elapidae Snake Venoms and Their Antivenom Neutralisation

Abstract

Snakebite envenoming is a neglected tropical disease (NTD) that results from the injection of snake venom of a venomous snake into animals and humans. In Africa (mainly in sub-Saharan Africa), over 100,000 envenomings and over 10,000 deaths per annum from snakebite have been reported. Difficulties in snakebite prevention and antivenom treatment are believed to result from a lack of epidemiological data and underestimated figures on snakebite envenoming-related morbidity and mortality. There are species- and genus-specific variations associated with snake venoms in Africa and across the globe. These variations contribute massively to diverse differences in venom toxicity and pathogenicity that can undermine the efficacy of adopted antivenom therapies used in the treatment of snakebite envenoming. There is a need to profile all snake venom proteins of medically important venomous snakes endemic to Africa. This is anticipated to help in the development of safer and more effective antivenoms for the treatment of snakebite envenoming within the continent. In this review, the proteomes of 34 snake venoms from the most medically important snakes in Africa, namely the Viperidae and Elipdae, were extracted from the literature. The toxin families were grouped into dominant, secondary, minor, and others based on the abundance of the protein families in the venom proteomes. The Viperidae venom proteome was dominated by snake venom metalloproteinases (SVMPs–41%), snake venom serine proteases (SVSPs–16%), and phospholipase A2 (PLA2–17%) protein families, while three-finger toxins (3FTxs–66%) and PLA2s (16%) dominated those of the Elapidae. We further review the neutralisation of these snake venoms by selected antivenoms widely used within the African continent. The profiling of African snake venom proteomes will aid in the development of effective antivenom against snakebite envenoming and, additionally, could possibly reveal therapeutic applications of snake venom proteins.

An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms

“…This is well exemplified by previous immunoprofiling studies applying microarrays ( Engmark et al, 2016 ) and enzyme-linked immunosorbent assay ( Lingam et al, 2020 ), as well as in vivo neutralization studies that showed viperid antivenoms are significantly more potent than elapid antivenoms ( Calvete et al, 2016 ; Ratanabanangkoon et al, 2016 ; Bailon Calderon et al, 2020 ; Faisal et al, 2021 ). This is likely due to most viperid venoms are predominated with high MW toxins (MW > 25 kDa) (e.g., SVMP and snake venom serine protease, SVSP) ( Offor et al, 2022 ), which are capable of eliciting stronger immune response for the production of neutralizing antibodies. However, given that venoms constituting neurotoxins of more than ∼40% failed to raise antivenoms with major improvement in neutralization efficacy ( Tan et al, 2015b ; Tan et al, 2016a ; Tan et al, 2019a ; Palasuberniam et al, 2021 ), it is therefore suggested that the low neutralizing efficacy of elapid antivenom may be also attributed to other factors, such as amino acid composition, that intrinsically modulate the epitope configuration of α-NTXs to be recognized by T-cell receptor (TCR) to elicit a strong humoral response.…”

Snake venom toxins: Potential anticancer therapeutics

“…To our knowledge, crotoxin PLA 2 is the only snake venom toxin that has shown promise through phase I clini- to enhance its efficacy, pharmacokinetics and pharmacodynamics as demonstrated in the production of cardiovascular drugs Enalapril (Faisal et al, 2021). Since inter-and intra-specific variations have also been reported in African snake venom toxins (Offor et al, 2022), it can be beneficial to also explore more anticancer testings with the snakes endemic within the continent.…”

“…These toxins can be short-chain, long-chain or non-conventional and are dominant in the venom of elapids (Kini & Doley, 2010;Offor et al, 2022). Table 5 shows the anticancer activities of 3FTxs from snake venoms.…”

“…The major protein families in the venom of most snake species include phospholipase A2 (PLA 2 ), three‐finger toxins (3FTx), snake venom metalloproteinases (SVMP) and snake venom serine proteases (SVSP) (Offor et al, 2022; Tasoulis & Isbister, 2017). Additionally, African elapids snake venoms are dominated by 3FTxs (66%) and PLA 2 (16%) protein families, while SVMPs (41%), SVSPs (16%) and PLA 2 (17%) are the dominant toxins in viperids (Offor et al, 2022).…”

“…The major protein families in the venom of most snake species include phospholipase A2 (PLA 2 ), three‐finger toxins (3FTx), snake venom metalloproteinases (SVMP) and snake venom serine proteases (SVSP) (Offor et al, 2022; Tasoulis & Isbister, 2017). Additionally, African elapids snake venoms are dominated by 3FTxs (66%) and PLA 2 (16%) protein families, while SVMPs (41%), SVSPs (16%) and PLA 2 (17%) are the dominant toxins in viperids (Offor et al, 2022). Other notable snake venom toxins with various clinical implications include L‐amino acid oxidase (L‐AAO), C‐type lectin (CTL), disintegrins (DIS), hyaluronidase (HYA), kunitz‐type serine protease inhibitor (KUN) and cystatin (CYS) (Tasoulis & Isbister, 2017).…”