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      Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery

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          Abstract

          Venomous animals have evolved toxins that interfere with specific components of their victim’s core physiological systems, thereby causing biological dysfunction that aids in prey capture, defense against predators, or other roles such as intraspecific competition. Many animal lineages evolved venom systems independently, highlighting the success of this strategy. Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. We provide examples of each of these areas of venom research, highlighting the potential that venom molecules hold for basic research and drug development.

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          The SARS-CoV-2 outbreak: what we know

          Highlights • The latest summary of the COVID-19 outbreak in China. • There might be an oral-fecal transmission of the virus. • Aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.
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            The future of peptide-based drugs.

            The suite of currently used drugs can be divided into two categories - traditional 'small molecule' drugs with typical molecular weights of 5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size, conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side-effects, whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them, but this comes at a cost of low bioavailability, poor membrane permeability, and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes, with the goal of combining advantages of small molecules (cost, conformational restriction, membrane permeability, metabolic stability, oral bioavailability) with those of proteins (natural components, target specificity, high potency). This article uses selected examples of peptides to highlight the importance of peptide drugs, some potential new opportunities for their exploitation, and some difficult challenges ahead in this field. © 2012 John Wiley & Sons A/S.
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              Genetic compensation triggered by mutant mRNA degradation

              Genetic robustness, or the ability of an organism to maintain fitness in the presence of mutations, can be achieved via protein feedback loops. Recent evidence suggests that organisms may also respond to mutations by upregulating related gene(s) independently of protein feedback loops, a phenomenon called transcriptional adaptation. However, the prevalence of transcriptional adaptation and its underlying molecular mechanisms are unknown. Here, by analyzing several models of transcriptional adaptation in zebrafish and mouse, we show a requirement for mRNA degradation. Alleles that fail to transcribe the mutated gene do not display transcriptional adaptation and exhibit more severe phenotypes than alleles displaying mutant mRNA decay. Transcriptome analysis reveals the upregulation of a substantial proportion of the genes that exhibit sequence similarity with the mutated gene’s mRNA, suggesting a sequence dependent mechanism. Besides implications for our understanding of disease-causing mutations, these findings will help design mutant alleles with minimal transcriptional adaptation-derived compensation.
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                Author and article information

                Contributors
                Journal
                Biochem Pharmacol
                Biochem. Pharmacol
                Biochemical Pharmacology
                Published by Elsevier Inc.
                0006-2952
                1873-2968
                12 June 2020
                12 June 2020
                : 114096
                Affiliations
                [a ]School of Science & Engineering, University of the Sunshine Coast, Sippy Downs, QLD Australia
                [b ]Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia
                Author notes
                [* ]Corresponding authors at: School of Science & Engineering, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Qld 4556, Australia(Volker Herzig), Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Road, St. Lucia, Qld 4072, Australia(Glenn F. King) vherzig@ 123456usc.edu.au glenn.king@ 123456imb.uq.edu.au
                Article
                S0006-2952(20)30332-4 114096
                10.1016/j.bcp.2020.114096
                7290223
                32535105
                c40e012b-c35e-43e4-96c9-bc8817fbecd8
                © 2020 Published by Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 13 May 2020
                : 6 June 2020
                : 9 June 2020
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                venom,venom peptides,pharmacological tools,drug discovery,therapeutics,insecticides

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