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      Antiviral peptides as promising therapeutic drugs

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          Abstract

          While scientific advances have led to large-scale production and widespread distribution of vaccines and antiviral drugs, viruses still remain a major cause of human diseases today. The ever-increasing reports of viral resistance and the emergence and re-emergence of viral epidemics pressure the health and scientific community to constantly find novel molecules with antiviral potential. This search involves numerous different approaches, and the use of antimicrobial peptides has presented itself as an interesting alternative. Even though the number of antimicrobial peptides with antiviral activity is still low, they already show immense potential to become pharmaceutically available antiviral drugs. Such peptides can originate from natural sources, such as those isolated from mammals and from animal venoms, or from artificial sources, when bioinformatics tools are used. This review aims to shed some light on antimicrobial peptides with antiviral activities against human viruses and update the data about the already well-known peptides that are still undergoing studies, emphasizing the most promising ones that may become medicines for clinical use.

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          Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3.

          Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species. (Blood. 2001;97:3951-3959)
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            Anti-microbial peptides: from invertebrates to vertebrates.

            Gene-encoded anti-microbial peptides (AMPs) are widespread in nature, as they are synthesized by microorganisms as well as by multicellular organisms from both the vegetal and the animal kingdoms. These naturally occurring AMPs form a first line of host defense against pathogens and are involved in innate immunity. Depending on their tissue distribution, AMPs ensure either a systemic or a local protection of the organism against environmental pathogens. They are classified into three major groups: (i) peptides with an alpha-helical conformation (insect cecropins, magainins, etc.), (ii) cyclic and open-ended cyclic peptides with pairs of cysteine residues (defensins, protegrin, etc.), and (iii) peptides with an over-representation of some amino acids (proline rich, histidine rich, etc.). Most AMPs display hydrophobic and cationic properties, have a molecular mass below 25-30 kDa, and adopt an amphipathic structure (alpha-helix, beta-hairpin-like beta-sheet, beta-sheet, or alpha-helix/beta-sheet mixed structures) that is believed to be essential to their anti-microbial action. Interestingly, in recent years, a series of novel AMPs have been discovered as processed forms of large proteins. Despite the extreme diversity in their primary and secondary structures, all natural AMPs have the in vitro particularity to affect a large number of microorganisms (bacteria, fungi, yeast, virus, etc.) with identical or complementary activity spectra. This review focuses on AMPs forming alpha-helices, beta-hairpin-like beta-sheets, beta-sheets, or alpha-helix/beta-sheet mixed structures from invertebrate and vertebrate origins. These molecules show some promise for therapeutic use.
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              Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications

              Summary Background Since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea was reported on 20th May 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. Previously published research on South Korea's MERS outbreak was limited to the early stages, when few data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate. Methods Data were obtained through the MERS portal by the Ministry for Health and Welfare (MOHW) and Korea Centres for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analysed for general characteristics, exposure source, timeline and infection generation. Sex, age and underlying diseases were analysed for the 38 deaths. Findings Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55 years, which was a little higher than the global average of 50 years. As in most other countries, more men than women were affected. The case fatality rate was 19.9%, which was lower than the global rate of 38.7% and the rate in Saudi Arabia (36.5%). In total, 184 patients were infected nosocomially and there were no community-acquired infections. The main underlying diseases were respiratory diseases, cancer and hypertension. The main contributors to the outbreak were late diagnosis, quarantine failure of ‘super spreaders’, familial care-giving and visiting, non-disclosure by patients, poor communication by the South Korean Government, inadequate hospital infection management, and ‘doctor shopping’. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.
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                Author and article information

                Contributors
                +55 06134487220 , ocfranco@gmail.com
                Journal
                Cell Mol Life Sci
                Cell. Mol. Life Sci
                Cellular and Molecular Life Sciences
                Springer International Publishing (Cham )
                1420-682X
                1420-9071
                17 May 2019
                2019
                : 76
                : 18
                : 3525-3542
                Affiliations
                [1 ]ISNI 0000 0001 2238 5157, GRID grid.7632.0, Universidade de Brasília, Pós-Graduação em Patologia Molecular, ; Campus Darcy Ribeiro, Brasília, DF 70910-900 Brazil
                [2 ]ISNI 0000 0001 1882 0945, GRID grid.411952.a, Centro de Análises Bioquímicas e Proteômicas, Pós-graduação em Ciências Genômicas e Biotecnologia, , Universidade Católica de Brasília, ; Brasília, DF 70790-160 Brazil
                [3 ]GRID grid.442132.2, S-Inova Biotech, Pós-graduação em Biotecnologia Universidade Católica Dom Bosco, ; Campo Grande, MS 79117-900 Brazil
                [4 ]ISNI 0000 0001 2322 4953, GRID grid.411206.0, Present Address: Departamento de Botânica e Ecologia, Instituto de Biociências, , Universidade Federal de Mato Grosso, ; Cuiabá, MT 78060-900 Brazil
                Author information
                http://orcid.org/0000-0001-9546-0525
                Article
                3138
                10.1007/s00018-019-03138-w
                7079787
                31101936
                0d6a6834-8c88-4ded-994c-5831eb373522
                © Springer Nature Switzerland AG 2019

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 21 January 2019
                : 4 May 2019
                : 7 May 2019
                Categories
                Review
                Custom metadata
                © Springer Nature Switzerland AG 2019

                Molecular biology
                natural peptides,rational design,human diseases,human viruses,drugs
                Molecular biology
                natural peptides, rational design, human diseases, human viruses, drugs

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