In essence, phage display technology simulates the human immune system in the lab, by employing libraries of antibody-displaying bacteriophages [41,44,45,46] to select for human antibody fragments in vitro . conceptualization of a novel therapeutic development strategy for biosynthetic oligoclonal antivenom (BOA) atorvastatin for snakebites based on recombinantly expressed oligoclonal mixtures of human monoclonal antibodies, possibly combined with repurposed small molecule enzyme inhibitors. strong class=”kwd-title” Keywords: snakebite envenoming, neglected tropical diseases, antivenom, next-generation antivenom, recombinant antivenom, small molecule inhibitors 1. Introduction Snakebite is a serious menace in tropical countries and was recognized as a neglected tropical disease by the World Health Organization in 2017 . Every year, more than 1.8C2.7 million cases of snakebite envenoming Rabbit polyclonal to ZCCHC12 in human victims occur, resulting in 80,000C140,000 deaths and at least twice as many disabling morbidities around the world . Most of the victims are in their productive age (between 20C40 years) and are often main breadwinners, leading to a great negative impact on the economics of their families. atorvastatin India has the highest number of deaths in the world due to snakebites (more than 46,000 ), predominantly caused by the big four snakes: Indian cobra ( em Naja naja /em ), Common krait ( em Bungarus caeruleus /em ), Russells viper ( em Daboia russelii /em ), and Saw-scaled viper ( em Echis carinatus /em ) . In October 2018, several like-minded basic scientists and clinicians came together at the Live and Let Live: Snakebite Cure Symposium at the Nextgen Genomics, Biology, Bioinformatics, and Technologies Conference in Jaipur, India to find a sustainable solution to the Indian snakebite envenoming challenge. Scientific discussions at this event concluded in agreement that the concept presented in this article is likely to be a promising avenue to follow for the development of next-generation antivenom with improved therapeutic properties. In this present concept, we propose the use of recombinant human antibodies and small molecule inhibitors atorvastatin to eventually replace horse-derived antivenoms (Figure 1). These next-generation treatments will have better efficacy and a reduced level of adverse reactions compared to current therapies. Open in a separate window Figure 1 Schematic overview of the manufacturing processes for antivenoms. (A) Conventional plasma-derived antivenoms are manufactured through a five-step process. (1) Snakes are milked to obtain venom. (2) The venom is used to immunize a horse (or in some cases a sheep). (3) Upon completion of the immunization process, blood is drawn from the horse. (4) Plasma and erythrocytes are separated, and different precipitation techniques are used to isolate IgG antibodies from the plasma. (5) Following concentration and formulation, the antivenom is bottled and ready for use. (B) In contrast, recombinant antivenoms based on monoclonal antibodies and/or antibody fragments can be developed through a very different, and much more defined, five-step process. (1) Different techniques are used to identify medically important venom toxins (e.g., toxicovenomics). (2) Using phage display selection (or other antibody discovery techniques), monoclonal antibodies are discovered against the medically relevant toxins. (3) Different formats of monoclonal antibodies may be combined to formulate an oligoclonal mixture of monoclonal antibodies that each target different key toxins. (4) The oligoclonal antibody mixture is manufactured using cell cultivation techniques, such as single-batch expression technologies. (5) Upon purification and formulation, the recombinant antivenom is bottled and ready for use. Drawbacks of conventional plasma-derived antivenoms and the corresponding benefits of recombinant antivenoms are presented in the right side of the figure. 2. Current Treatment for Snakebite Victims Snakebite envenoming is a severe medical emergency that can cause multiple organ failure. Thus, it requires quick and timely treatment of the victims. Currently, the only accepted treatment for snakebite envenomings involves intravenous administration of conventional antivenoms, which comprise antibodies or antibody fragments derived.
- Next Furthermore, targeting PI3K signaling continues to be also been shown to be a promising anti-fibrotic treatment technique using IPF patient-derived PCLS 
- Previous [PMC free content] [PubMed] [Google Scholar] 9
- Among Hungarians, PTA was 33
- Results are presented as mean S
- p? ?0
- In the case of cardiovascular symptoms/signs, recent ECG changes, or troponin increase 99th percentile of the upper reference limit provided by the manufacturing companies, patients were referred to our center for workup
- The homology magic size with the best contact score was selected, and steepest-descent energy minimization protocols were applied (AMBER14:EHT force field)