scholarly journals Antivirals against the Chikungunya Virus

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1307
Author(s):  
Verena Battisti ◽  
Ernst Urban ◽  
Thierry Langer
Keyword(s):  
Research And Development ◽  
Small Molecule ◽  
Joint Pain ◽  
Large Scale ◽  
Chikungunya Virus ◽  
Febrile Disease ◽  
Chikv Infection ◽  
Chronic Stage ◽  
Molecule Inhibitor ◽  
The World

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has re-emerged in recent decades, causing large-scale epidemics in many parts of the world. CHIKV infection leads to a febrile disease known as chikungunya fever (CHIKF), which is characterised by severe joint pain and myalgia. As many patients develop a painful chronic stage and neither antiviral drugs nor vaccines are available, the development of a potent CHIKV inhibiting drug is crucial for CHIKF treatment. A comprehensive summary of current antiviral research and development of small-molecule inhibitor against CHIKV is presented in this review. We highlight different approaches used for the identification of such compounds and further discuss the identification and application of promising viral and host targets.

scholarly journals Fatty Acid Synthase Promotes the Palmitoylation of Chikungunya Virus nsP1

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
Na Zhang ◽  
Hongjian Zhao ◽  
Leiliang Zhang
Keyword(s):  
Plasma Membrane ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Zinc Finger ◽  
Posttranslational Modification ◽  
Joint Pain ◽  
Chikungunya Virus ◽  
Fatty Acid Synthase ◽  
Chikv Infection ◽  
Important Form

ABSTRACT Chikungunya virus (CHIKV) is transmitted to people by mosquitoes, and CHIKV infection causes fever and joint pain. Fatty acid synthase (FASN) has been identified as a proviral factor for CHIKV. How FASN participates in CHIKV replication remains to be elucidated. In this study, we demonstrated that palmitic acid (PA) can restore the suppression of CHIKV replication by FASN inhibitors. The palmitoylation and plasma membrane localization of CHIKV nsP1 were reduced by FASN inhibitors. Triple mutation of Cys417, Cys418, and Cys419 in nsP1 blocked its palmitoylation and severely disrupted CHIKV replication. Furthermore, two zinc finger DHHC domain-containing palmitoyltransferases (ZDHHCs), ZDHHC2 and ZDHHC19, promoted nsP1 palmitoylation and CHIKV replication. Our results not only identified the key enzymes for the palmitoylation of nsP1 but also provided mechanistic insights into the roles of FASN in CHIKV replication. IMPORTANCE S-palmitoylation is an important form of lipid posttranslational modification, which affects the function of proteins by regulating their transport, stability, and localization. Previous studies have shown that FASN is critical for CHIKV replication; however, the mechanism for this function of FASN remains unknown. The key zinc finger DHHC domain-containing palmitoyltransferases involved in the palmitoylation of nsP1 are not clear. We demonstrated that FASN promoted CHIKV replication through nsP1 palmitoylation. ZDHHC2 and ZDHHC19 were identified as the major enzymes for nsP1 palmitoylation. Since nsP1 proteins are conserved in alphaviruses, our results highlight the mechanisms by which alphavirus nsP1 is palmitoylated.

scholarly journals Evaluation of DNA-Launched Virus-Like Particle Vaccines in an Immune Competent Mouse Model of Chikungunya Virus Infection

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 345
Author(s):  
Jonathan O. Rayner ◽  
Jin Hyun Kim ◽  
Rosemary W. Roberts ◽  
Raphael Ryan Wood ◽  
Brian Fouty ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Vaccine Development ◽  
Immunocompetent Mouse ◽  
Chikv Infection ◽  
Male And Female ◽  
Preclinical Evaluation ◽  
Virus Like Particle ◽  
The World ◽  
Immunocompetent Mice ◽  
Immune Competent Mouse

Chikungunya virus (CHIKV) infection can result in chronic and debilitating arthralgia affecting humans in tropical and subtropical regions around the world, yet there are no licensed vaccines to prevent infection. DNA launched virus like particle (VLP) vaccines represent a potentially safer alternative to traditional live-attenuated vaccines; however, fully characterized immunocompetent mouse models which appropriately include both male and female animals for preclinical evaluation of these, and other, vaccine platforms are lacking. Utilizing virus stocks engineered to express mutations reported to enhance CHIKV virulence in mice, infection of male and female immunocompetent mice was evaluated, and the resulting model utilized to assess the efficacy of candidate DNA launched CHIKV VLP vaccines. Results demonstrate the potential utility of DNA launched VLP vaccines in comparison to a live attenuated CHIKV vaccine and identify gender differences in viral RNA loads that impact interpretation of vaccine efficacy and may have important implications for future CHIKV vaccine development.

scholarly journals Chronic Joint Pain 3 Years after Chikungunya Virus Infection Largely Characterized by Relapsing-remitting Symptoms

2019 ◽  
Vol 47 (8) ◽  
pp. 1267-1274 ◽  
Author(s):  
Sarah R. Tritsch ◽  
Liliana Encinales ◽  
Nelly Pacheco ◽  
Andres Cadena ◽  
Carlos Cure ◽  
...  
Keyword(s):  
Latin American ◽  
High Frequency ◽  
Joint Pain ◽  
Chikungunya Virus ◽  
Morning Stiffness ◽  
Common Type ◽  
Chikv Infection ◽  
Cross Sectional ◽  
Relapsing Remitting ◽  
Initial Cohort

Objective.To determine the frequency of chronic joint pain and stiffness 3 years after infection with chikungunya virus (CHIKV) in a Latin American cohort.Methods.A cross-sectional followup of 120 patients from an initial cohort of 500 patients who reported joint pain 2 years after infection from the Atlántico Department, Colombia. Patients were clinically diagnosed as having CHIKV during the 2014–2015 epidemic, and baseline and followup symptoms at 40 months were evaluated in serologically confirmed cases.Results.Of the initial 500 patients enrolled in the study, 482 had serologically confirmed chikungunya infection. From this group, 123 patients reported joint pain 20 months after infection, and 54% of those patients reported continued joint pain 40 months after infection. Therefore, 1 out of every 8 people who tested serologically positive for CHIKV infection had persistent joint pain 3 years after infection. Participants who followed up in person were predominantly adult (mean ± SD age 51 ± 14 yrs) and female (86%). The most common type of pain reported in these patients at 40 months post-infection was pain with periods of relief and subsequent reoccurrence, and over 75% reported stiffness after immobility, with 39% experiencing morning stiffness.Conclusion.To our knowledge, this is the first report to describe persistent joint pain and stiffness 40 months after viral infection. The high frequency of chronic disease highlights the need to develop prevention and treatment methods. Further studies should be conducted to understand the similarities between post-chikungunya joint pain and rheumatoid arthritis.

scholarly journals Origins, pathophysiology, diagnosis, vaccination and prevention of Chikungunya virus

2019 ◽  
Vol 32 (1) ◽  
pp. 40-44
Author(s):  
Md. Rajdoula Rafe ◽  
Syeda Naureen Ahmed ◽  
Zebunnesa Ahmed
Keyword(s):  
Effective Treatment ◽  
Skin Rash ◽  
Joint Pain ◽  
Chikungunya Virus ◽  
Literature Search ◽  
Public Awareness ◽  
Extensive Literature ◽  
Treatment And Prevention ◽  
The World ◽  
Extensive Literature Search

Abstract Chikungunya virus is an Alphavirus that possesses characteristics similar to that of an arthropod-borne virus. Chikungunya virus has been one of the major concerns for the last few decades due to its nature of explosive spreading throughout the world. This article is intended to give detailed information about Chikungunya virus, and includes its pathogenesis, origins, diagnosis, treatment and prevention. Although, recent researches suggests various approaches to treating Chikungunya virus, extensive literature search on Chikungunya virus has revealed that, currently, there is no effective treatment available and the virus is greatly dependent on its vectors. Patients affected by Chikungunya virus mainly show symptoms of fever, arthralgia, joint pain and skin rash. Since there is no effective treatment available, public awareness is the most significant factor for potential prevention against Chikungunya virus.

scholarly journals Acute-Phase Levels of CXCL8 as Risk Factor for Chronic Arthralgia Following Chikungunya Virus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Leile Camila Jacob-Nascimento ◽  
Caroline Xavier Carvalho ◽  
Monaíse Madalena Oliveira Silva ◽  
Mariana Kikuti ◽  
Rosângela Oliveira Anjos ◽  
...  
Keyword(s):  
Acute Phase ◽  
Joint Pain ◽  
Chikungunya Virus ◽  
Healthy Controls ◽  
Sample Collection ◽  
Chikv Infection ◽  
Flow Cytometric ◽  
Multivariable Analyses ◽  
Ifn Γ

The immunopathogenesis of chikungunya virus (CHIKV) infection and the role of acute-phase immune response on joint pain persistence is not fully understood. We investigated the profile of serum chemokine and cytokine in CHIKV-infected patients with acute disease, compared the levels of these biomarkers to those of patients with other acute febrile diseases (OAFD) and healthy controls (HC), and evaluated their role as predictors of chronic arthralgia development. Chemokines and cytokines were measured by flow Cytometric Bead Array. Patients with CHIKV infection were further categorized according to duration of arthralgia (≤ 3 months vs >3 months), presence of anti-CHIKV IgM at acute-phase sample, and number of days of symptoms at sample collection (1 vs 2-3 vs ≥4). Patients with acute CHIKV infection had significantly higher levels of CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1β, IL-6, IL-12, and IL-10 as compared to HC. CCL2, CCL5, and CXCL10 levels were also significantly higher in patients with CHIKV infection compared to patients with OAFD. Patients whose arthralgia lasted > 3 months had increased CXCL8 levels compared to patients whose arthralgia did not (p<0.05). Multivariable analyses further indicated that high levels of CXCL8 and female sex were associated with arthralgia lasting >3 months. Patients with chikungunya and OAFD had similar cytokine kinetics for IL-1β, IL-12, TNF, IFN-γ, IL-2, and IL-4, although the levels were lower for CHIKV patients. This study suggests that chemokines may have an important role in the immunopathogenesis of chronic chikungunya-related arthralgia.

scholarly journals Chikungunya Virus Infection Impairs the Function of Osteogenic Cells

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Enakshi Roy ◽  
Wen Shi ◽  
Bin Duan ◽  
St Patrick Reid
Keyword(s):  
Osteogenic Differentiation ◽  
Joint Pain ◽  
Chikungunya Virus ◽  
Bone Homeostasis ◽  
Bone Pathology ◽  
Chikv Infection ◽  
Matrix Mineralization ◽  
Osteogenic Cells ◽  
And Function ◽  
First Time

ABSTRACT Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus spread by the Aedes species of mosquito. Chikungunya virus causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal the presence of bone lesions and erosive arthritis in the joints of CHIKV-infected patients, indicating an association of bone pathology with CHIKV infection. However, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Bone marrow-derived mesenchymal stem cells (BMSCs) contribute to bone homeostasis by differentiating into osteogenic cells which later mature to form the bone. Disruption of osteogenic differentiation and function of BMSCs leads to bone pathologies. Studies show that virus infections can alter the properties and function of BMSCs. However, to date, pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMSCs and osteogenic cells to CHIKV and studied the effect of infection on these cells. For the first time to our knowledge, we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed decreased gene expression of the major regulator of osteogenic differentiation, RUNX2, in CHIKV-infected osteogenic cells. Furthermore, impaired functional properties of osteogenic cells, i.e., decreased production and activity of alkaline phosphatase (ALP) and matrix mineralization, were observed in the presence of CHIKV infection. Thus, we conclude that CHIKV likely impairs osteogenic differentiation of BMSCs, indicating a possible role of BMSCs in altering bone homeostasis during CHIKV infection. IMPORTANCE Presently, no vaccines or treatment options are available for CHIKV infection. Joint pain is one of the major concerns. Although studies have shown an association between bone pathology and infection, the molecular pathogenesis in the context of bone pathology is poorly defined. Here, we demonstrate for the first time that BMSCs and BMSC-derived osteogenic cells are susceptible to CHIKV infection, and that infection likely alters the function of osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.

scholarly journals Small-Molecule Inhibitors of Chikungunya Virus: Mechanisms of Action and Antiviral Drug Resistance

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Kristina Kovacikova ◽  
Martijn J. van Hemert
Keyword(s):  
Drug Resistance ◽  
Small Molecule ◽  
Large Scale ◽  
Chikungunya Virus ◽  
Small Molecule Inhibitors ◽  
Antiviral Treatment ◽  
Antiviral Drug ◽  
Current Status ◽  
Antiviral Drug Resistance

ABSTRACT Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has spread to more than 60 countries worldwide. CHIKV infection leads to a febrile illness known as chikungunya fever (CHIKF), which is characterized by long-lasting and debilitating joint and muscle pain. CHIKV can cause large-scale epidemics with high attack rates, which substantiates the need for development of effective therapeutics suitable for outbreak containment. In this review, we highlight the different strategies used for developing CHIKV small-molecule inhibitors, ranging from high-throughput cell-based screening to in silico screens and enzymatic assays with purified viral proteins. We further discuss the current status of the most promising molecules, including in vitro and in vivo findings. In particular, we focus on describing host and/or viral targets, mode of action, and mechanisms of antiviral drug resistance and associated mutations. Knowledge of the key molecular determinants of drug resistance will aid selection of the most promising antiviral agent(s) for clinical use. For these reasons, we also summarize the available information about drug-resistant phenotypes in Aedes mosquito vectors. From this review, it is evident that more of the active molecules need to be evaluated in preclinical and clinical models to address the current lack of antiviral treatment for CHIKF.

scholarly journals Chikungunya virus infection impairs the function of osteogenic cells

2020 ◽  
Author(s):  
Enakshi Roy ◽  
Wen Shi ◽  
Bin Duan ◽  
St Patrick Reid
Keyword(s):  
Osteogenic Differentiation ◽  
Joint Pain ◽  
Chikungunya Virus ◽  
Bone Homeostasis ◽  
Bone Pathology ◽  
Chikv Infection ◽  
Matrix Mineralization ◽  
Osteogenic Cells ◽  
And Function ◽  
First Time

AbstractChikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus, spread by the Aedes species (sp.) mosquitoes. Chikungunya virus (CHIKV) causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal presence of bone lesions and erosive arthritis in the joints of CHIKV infected patients, indicating an association of bone pathology with CHIKV infection. However, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Bone marrow derived mesenchymal stem cells (BMSCs) contribute to bone homeostasis by differentiating into osteogenic cells which later mature to form the bone. Disruption of osteogenic differentiation and function of BMSCs lead to bone pathologies. Studies show that virus infections can alter the properties and function of BMSCs. However, to date, pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMSCs and osteogenic cells to CHIKV and studied the effect of infection on these cells. To our knowledge, for the first time we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed a decreased gene expression of the major regulator of osteogenic differentiation, RUNX2 in CHIKV infected osteogenic cells. Furthermore, impaired functional properties of osteogenic cells i.e. decreased production and activity of alkaline phosphatase (ALP) and matrix mineralization were observed in the presence of CHIKV infection. Thus, we conclude that CHIKV likely impairs osteogenic differentiation of BMSCs indicating a possible role of BMSCs in altering bone homeostasis during CHIKV infection.ImportancePresently, no vaccines or treatment options are available for CHIKV infection. Joint pain is one of the major concerns. Although studies have shown an association between bone pathology and infection, the molecular pathogenesis in context of bone pathology is poorly defined. Here, we demonstrate for the first time that BMSCs and BMSC-derived osteogenic cells are susceptible to CHIKV infection and infection likely alters function of the osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.

TO THE QUESTION OF RESPONSIBILITY FOR TORTURE IN THE RUSSIAN FEDERATION

2020 ◽  
Vol 10 (2) ◽  
pp. 103-106
Author(s):  
ASTEMIR ZHURTOV ◽  
Keyword(s):  
Human Rights ◽  
Russian Federation ◽  
Large Scale ◽  
Human Life ◽  
International Standards ◽  
World Community ◽  
The World ◽  
Long Time ◽  
Protection Of Human Rights ◽  
The Russian Federation

Cruel and inhumane acts that harm human life and health, as well as humiliate the dignity, are prohibited in most countries of the world, and Russia is no exception in this issue. The article presents an analysis of the institution of responsibility for torture in the Russian Federation. The author comes to the conclusion that the current criminal law of Russia superficially and fragmentally regulates liability for torture, in connection with which the author formulated the proposals to define such act as an independent crime. In the frame of modern globalization, the world community pays special attention to the protection of human rights, in connection with which large-scale international standards have been created a long time ago. The Universal Declaration of Human Rights and other international acts enshrine prohibitions of cruel and inhumane acts that harm human life and health, as well as degrade the dignity.Considering the historical experience of the past, these standards focus on the prohibition of any kind of torture, regardless of the purpose of their implementation.

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