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      Recent Advances in Crimean-Congo Hemorrhagic Fever Virus Detection, Treatment, and Vaccination: Overview of Current Status and Challenges

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          Abstract

          Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus, and zoonosis, and affects large regions of Asia, Southwestern and Southeastern Europe, and Africa. CCHFV can produce symptoms, including no specific clinical symptoms, mild to severe clinical symptoms, or deadly infections. Virus isolation attempts, antigen-capture enzyme-linked immunosorbent assay (ELISA), and reverse transcription polymerase chain reaction (RT-PCR) are all possible diagnostic tests for CCHFV. Furthermore, an efficient, quick, and cheap technology, including biosensors, must be designed and developed to detect CCHFV. The goal of this article is to offer an overview of modern laboratory tests available as well as other innovative detection methods such as biosensors for CCHFV, as well as the benefits and limits of the assays. Furthermore, confirmed cases of CCHF are managed with symptomatic assistance and general supportive care. This study examined the various treatment modalities, as well as their respective limitations and developments, including immunotherapy and antivirals. Recent biotechnology advancements and the availability of suitable animal models have accelerated the development of CCHF vaccines by a substantial margin. We examined a range of potential vaccines for CCHF in this research, comprising nucleic acid, viral particles, inactivated, and multi-epitope vaccines, as well as the present obstacles and developments in this field. Thus, the purpose of this review is to present a comprehensive summary of the endeavors dedicated to advancing various diagnostic, therapeutic, and preventive strategies for CCHF infection in anticipation of forthcoming hazards.

          Graphical Abstract

          For the protection of medical personnel and effective case management, an early diagnosis of Crimean-Congo hemorrhagic fever (CCHF) is critical. CCHF is diagnosed through laboratory procedures such as RT-PCR, ELISA, virus isolation attempts, and ELISA detection of IgG and IgM antibodies. This review examines several biomarkers researched for their potential use in the diagnosis and prognosis of critical viral infections. It also explores the utility of more traditional diagnostic markers in predicting secondary complications, distinguishing Crimean-Congo hemorrhagic fever virus (CCHFV) infection, and serving as severity indicators. CCHFV vaccine development is advancing at an accelerated rate, facilitated by the availability of a lethal animal infection model. Hence, this review aims to furnish a comprehensive synopsis of the endeavors devoted to various vaccine candidates utilizing distinct approaches against CCHFV. These candidates comprise inactivated, virus-like particles, recombinant proteins, and nucleic acid vaccines. Furthermore, supportive therapy serves as the principal modality of treatment. Human cases of CCHF have been treated with ribavirin, a broad-spectrum antiviral medication; nevertheless, the therapeutic advantages of this intervention remain elusive. This article analyzes the present advancements and prospective trajectories in the realm of antiviral approaches targeting CCHFV.

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          Development of an inactivated vaccine candidate for SARS-CoV-2

          The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.
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            Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.

            Crimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review the features of CCHF, including the clinical syndrome, diagnosis, treatment, pathogenesis, vaccine development and laboratory animal models of CCHF. The paper ends with a discussion of the possible future geographic range of the virus. For the benefit of researchers, we include a Supplementary Table listing all published reports of CCHF cases and outbreaks in the English-language literature, plus some principal articles in other languages, with total case numbers, case fatality rates and all CCHFV strains on GenBank. Copyright © 2013 Elsevier B.V. All rights reserved.
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              Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics

              Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th–20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.
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                Author and article information

                Contributors
                rahadianzmsiphd@fmipa.unp.ac.id
                Yassaman124@gmail.com
                Journal
                Biol Proced Online
                Biol Proced Online
                Biological Procedures Online
                BioMed Central (London )
                1480-9222
                26 June 2024
                26 June 2024
                2024
                : 26
                : 20
                Affiliations
                [1 ]Department of Public Health, College of Applied Medical Sciences, King Khalid University, ( https://ror.org/052kwzs30) Khamis Mushait Campus, Abha, 62561 Saudi Arabia
                [2 ]Medical Faculty, University of Georgi, ( https://ror.org/00te3t702) Tbilisi, Georgia
                [3 ]Department of Pharmacy, Mazaya University College, ( https://ror.org/058arh533) Dhi Qar, Iraq
                [4 ]Azad Researcher, Virology and Biotechnology, Tehran, Iran
                [5 ]Collage of Pharmacy, National University of Science and Technology, Dhi Qar, 64001 Iraq
                [6 ]Scientific Affairs Department, Al-Mustaqbal University, Hillah, Babylon, 51001 Iraq
                [7 ]Optics techniques department, health and medical techniques college, Al-Noor University, Mosul, Iraq
                [8 ]Department of Biotechnology, Institute of Science, Uskudar University, ( https://ror.org/02dzjmc73) Istanbul, Turkey
                [9 ]Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, ( https://ror.org/04jrfgq66) Padang, Indonesia
                [10 ]Center for Advanced Material Processing, Artificial Intelligence, and Biophysics Informatics (CAMPBIOTICS), Universitas Negeri Padang, ( https://ror.org/04jrfgq66) Padang, Indonesia
                Article
                244
                10.1186/s12575-024-00244-3
                11201903
                38926669
                1ff09b78-52dd-4baf-b7fb-8f69cc1c1b70
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 29 February 2024
                : 16 May 2024
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                Review
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                © BioMed Central Ltd., part of Springer Nature 2024

                Life sciences
                crimean-congo hemorrhagic fever virus (cchfv),detection,treatment,vaccination
                Life sciences
                crimean-congo hemorrhagic fever virus (cchfv), detection, treatment, vaccination

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