Abstract
For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.Key ContributionThis review describes the state of the art in snake venom-derived peptides and their therapeutic applications. This work reinforces the potential of snake venom components as therapeutic agents, particularly in the quest for new antimicrobial and anticancer drugs.
Highlights
Snakes are arguably among if not the most despised creatures in the entire animal kingdom.With some exceptions, for the vast majority of people, snakes epitomize harm, evil, and treachery.Examples are found in scriptures and ancient tradition, classic literature (e.g., Poe’s The cask of amontillado, Doyle’sThe Speckled Band) or colloquial language (“he’s a snake in the grass”)
A pioneering example was the development of Captopril® from a peptide discovered in the venom of the Brazilian pit viper Bothrops jararaca [2,3], and subsequent development of angiotensin-converting enzyme (ACE)
Meaningful progress has been made in cancer research, new therapeutic alternatives are still required in order to avoid undesired effects linked to current therapies and to target multidrug-resistant cells [158,159]
Summary
Snakes are arguably among if not the most despised creatures in the entire animal kingdom. In addition to the direct cytotoxic effect, the immunomodulatory properties of Ctn have been explored, showing an overall pro-inflammatory profile in the presence of heat-inactivated bacterial antigens and IFN-γ [110], contrasting with general anti-inflammatory behavior of other SV-CATHs. From a structural viewpoint, circular dichroism and nuclear magnetic resonance (NMR) studies indicate that Ctn is fully in a random-coil conformation in aqueous solution, but may change its structure in membrane-like environments (i.e., dodecylphosphocholine micelles), displaying an α-helix conformation at the N-terminal end (residues 3 – 21) plus a C-terminal random coil tail (Figure 3a) [107].
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