scholarly journals Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 850
Author(s):  
Sahil Jain ◽  
Svetlana F. Khaiboullina ◽  
Manoj Baranwal
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Cell Types ◽  
Host Cells ◽  
Humoral Immune ◽  
T Cell Apoptosis ◽  
Treatment Measures ◽  
Ebov Infection ◽  
Zaire Ebolavirus ◽  
Potential Factors

Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola virus disease (EVD), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. There are three EBOV outbreaks documented in the last six years resulting in significant morbidity (>32,000 cases) and mortality (>13,500 deaths). The potential factors contributing to the high infectivity of this virus include multiple entry mechanisms, susceptibility of the host cells, employment of multiple immune evasion mechanisms and rapid person-to-person transmission. EBOV infection leads to cytokine storm, disseminated intravascular coagulation, host T cell apoptosis as well as cell mediated and humoral immune response. In this review, a concise recap of cell types targeted by EBOV and EVD symptoms followed by detailed run-through of host innate and adaptive immune responses, virus-driven regulation and their combined effects contributing to the disease pathogenesis has been presented. At last, the vaccine and drug development initiatives as well as challenges related to the management of infection have been discussed.

scholarly journals Inflammatory and Humoral Immune Response during Ebola Virus Infection in Survivor and Fatal Cases Occurred in Sierra Leone during the 2014–2016 Outbreak in West Africa

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 373 ◽  
Author(s):  
Francesca Colavita ◽  
Mirella Biava ◽  
Concetta Castilletti ◽  
Simone Lanini ◽  
Rossella Miccio ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Sierra Leone ◽  
Ebola Virus ◽  
Virus Disease ◽  
Late Phase ◽  
Treatment Center ◽  
Humoral Immune ◽  
Western Africa ◽  
Ebov Infection

Ebola virus (EBOV) infection is characterized by an excessive inflammatory response, a loss of lymphocytes and a general paralysis of the immune system, however pathophysiological mechanisms are not fully understood. In a cohort of 23 fatal and 21 survivors of ebola virus disease (EVD) cases admitted to the Emergency Ebola-Treatment-Center in Goderich (Freetown, Sierra Leone) during the 2014 to 2016 EBOV epidemic in Western Africa, we analyzed the pathway-focused gene expression profile of secreted proteins involved in the immune response and the levels of specific anti-EBOV IgM and IgG from the time of admission till discharge or death. We observed a dysregulated inflammatory response in fatal patients as compared to survivors, mainly consisting of the upregulation of inflammatory mediators, whose extent directly correlated with viremia levels. The upregulation persisted and intensified during the late phase of infection. Relevant differences were also found in humoral immunity, as an earlier and more robust EBOV antibody response was observed in survivor patients.

scholarly journals Screening of terpenoids as potential therapeutics against Zaire ebolavirus infection through pharmacophore-based drug design

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1040
Author(s):  
Ade Hanna Natalia ◽  
Usman Sumo Friend Tambunan
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Molecular Interactions ◽  
Ebola Virus ◽  
Virus Disease ◽  
Docking Simulation ◽  
Host Cells ◽  
Virus Species ◽  
Docking Simulations ◽  
Zaire Ebolavirus

Backgroud: Ebola virus disease (EVD) has spread to various countries in the world and has caused many deaths. Five different virus species can cause EVD, but the most virulent is Zaire ebolavirus (EBOV). The genome of EBOV includes seven genes that encode proteins playing essential roles in the virus lifecycle. Among these proteins, VP24 plays a vital role in the inhibition of the host cells’ immune system. Therefore, VP24 is a potential target for EVD therapy. In the present study, a potential inhibitor of EBOV VP24 activity was identified through pharmacophore-based drug design. Methods: This research was a in silico study, using pharmacophore based molecular docking simulation to obtain inhibitor candidates. Result: Terpenoids were used as VP24 inhibitor candidates. In particular, 55,979 terpenoids were obtained from the PubChem database. An initial screening based on the toxicity prediction test was performed with DataWarrior software: 3,353 ligands were shown to have a favorable toxicity profile, but only 1,375 among them had suitable pharmacophore features. These ligands were used for pharmacophore-based rigid and flexible molecular docking simulations with PDB ID: 4M0Q, chosen as the crystal structure of EBOV VP24. Six ligands predicted to have strong molecular interactions with EBOV VP24 underwent pharmacological property analysis through various software packages, including DataWarrior, SwissADME, admetSAR, pkCSM, and Toxtree. Conclusions: Taxumairol V was identified as the best candidate for EVD drug therapy via EBOV VP24 inhibition based on its molecular properties, predicted molecular interactions with the target molecule, and predicted pharmacological properties.

scholarly journals Identification of Diaryl-Quinoline Compounds as Entry Inhibitors of Ebola Virus

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 678 ◽  
Author(s):  
Qinghua Cui ◽  
Han Cheng ◽  
Rui Xiong ◽  
Gang Zhang ◽  
Ruikun Du ◽  
...  
Keyword(s):  
Drug Development ◽  
Ebola Virus ◽  
Virus Disease ◽  
Virus Entry ◽  
Surface Protein ◽  
Host Cells ◽  
Entry Inhibitor ◽  
Entry Inhibitors ◽  
Promising Target ◽  
Virus Entry Inhibitors

Ebola virus is the causative agent of Ebola virus disease in humans. The lethality of Ebola virus infection is about 50%, supporting the urgent need to develop anti-Ebola drugs. Glycoprotein (GP) is the only surface protein of the Ebola virus, which is functionally critical for the virus to attach and enter the host cells, and is a promising target for anti-Ebola virus drug development. In this study, using the recombinant HIV-1/Ebola pseudovirus platform we previously established, we evaluated a small molecule library containing various quinoline compounds for anti-Ebola virus entry inhibitors. Some of the quinoline compounds specifically inhibited the entry of the Ebola virus. Among them, compound SYL1712 was the most potent Ebola virus entry inhibitor with an IC50 of ~1 μM. The binding of SYL1712 to the vial glycoprotein was computationally modeled and was predicted to interact with specific residues of GP. We used the time of the addition assay to show that compound SYL1712 blocks Ebola GP-mediated entry. Finally, consistent with being an Ebola virus entry inhibitor, compound SYL1712 inhibited infectious Ebola virus replication in tissue culture under biosafety level 4 containment, with an IC50 of 2 μM. In conclusion, we identified several related molecules with a diaryl-quinoline scaffold as potential anti-EBOV entry inhibitors, which can be further optimized for anti-Ebola drug development.

scholarly journals Statins Suppress Ebola Virus Infectivity by Interfering with Glycoprotein Processing

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Punya Shrivastava-Ranjan ◽  
Mike Flint ◽  
Éric Bergeron ◽  
Anita K. McElroy ◽  
Payel Chatterjee ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Statin Treatment ◽  
Ebola Virus Disease ◽  
Health Concern ◽  
Virus Infectivity ◽  
Viral Glycoprotein ◽  
Antiviral Effects ◽  
Ebov Infection ◽  
Glycoprotein Processing

ABSTRACTEbola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013–2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infectionin vitro. Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD.IMPORTANCETreatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune system are characteristic features of EVD, statins could be explored as part of EVD therapeutics.

Characterization of an Anti-Ebola virus Hyperimmune Globulin Derived from Convalescent Plasma

2021 ◽  
Author(s):  
Jonathan M Ciencewicki ◽  
Andrew S Herbert ◽  
Nadia Storm ◽  
Nicole M Josleyn ◽  
Kathleen Huie ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Fold Increase ◽  
Surface Glycoprotein ◽  
Post Exposure Prophylaxis ◽  
Emerging Viruses ◽  
Live Virus ◽  
Glycoprotein Antigen ◽  
Ebov Infection ◽  
Exposure Prophylaxis

Abstract Backrgound Convalescent plasma has been used to treat many viral diseases including Ebola. The manufacture of a purified anti-Ebola virus (EBOV) intravenous immunoglobulin (IVIG) from pooled convalescent plasma is described in this paper. Methods An ELISA targeting an EBOV surface glycoprotein antigen was used to determine the immunoglobulin titer of pooled plasma and purified anti-EBOV IVIG. Anti-EBOV IVIG was also tested in neutralization assays using a vesicular stomatitis virus pseudovirion expressing EBOV glycoprotein on its surface and with live EBOV. Finally, the efficacy of the anti-EBOV IVIG was assessed in a mouse model of EBOV infection. Results In the ELISA, the anti-EBOV IVIG was shown to have a seven-fold increase in IgG titer over pooled convalescent plasma. In both the pseudovirion and live virus assays, the anti-EBOV IVIG showed approximately five- to six-fold increased potency over pooled plasma. Anti-EBOV IVIG also significantly improved survivability in mice infected with the virus when administered concurrently or two days after infection. Conclusions These data support this purified anti-EBOV IVIG merits additional investigation and clinical trials for treatment and post-exposure prophylaxis of Ebola virus disease. The experience gained can be applied to manufacture hyperimmune globulins against other emerging viruses.

scholarly journals P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity

2021 ◽  
Vol 17 (6) ◽  
pp. e1009616
Author(s):  
Linliang Zhang ◽  
Shixiong Zhou ◽  
Majuan Chen ◽  
Jie Yan ◽  
Yi Yang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Regulatory Mechanism ◽  
Physiological Effect ◽  
Host Cells ◽  
Post Translational Modifications ◽  
Virus Life Cycle ◽  
The Matrix ◽  
Zaire Ebolavirus

The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.

scholarly journals Recurrent outbreaks of Ebola Virus Disease in Africa: A Meta-analysis of case fatality rates

2020 ◽  
Author(s):  
Joseph Kawuki ◽  
Taha Hussein Musa ◽  
Xiaojin Yu
Keyword(s):  
Ebola Virus ◽  
Assessment Tool ◽  
Virus Disease ◽  
Control Strategies ◽  
Meta Analysis ◽  
Case Fatality ◽  
Ebola Virus Disease ◽  
Surveillance Systems ◽  
Potential Factors ◽  
English Articles

Abstract Background: In the last decade, Africa has witnessed several outbreaks of Ebola virus disease (EVD), each presenting with varying case fatality rate (CFR) and other socio-economic impacts. This study aims to summarise the CFR and identify potential factors that influenced the severity of EVD outbreaks in Africa.Methods: This was a systematic review and meta-analysis of EVD outbreaks published between January 2010 and March 2020, using Web of Science, Scopus and PubMed databases. Only English articles and reports, including the number of cases and deaths during the outbreak in Africa, were considered. Quality of the included articles was assessed using the Murad’s quality assessment tool. The analysis was conducted using Stata (version 12), pooled effect sizes were calculated using the random-effects model and heterogeneity was tested for using the I2 statistic.Result: Thirteen studies with 32,300 cases and 13,727 deaths were identified whose pooled CFR was 60% (95% CI: 47-73%). The most EVD-affected countries were DRC with 5 outbreaks and a pooled CFR of 65% (95% CI: 59-71%), followed by Uganda with 3 outbreaks and CFR= 83% (95% CI: 60-99%). Zaire ebolavirus caused the most outbreaks (10), with a CFR= 58% (95% CI: 45-71%). Besides, outbreaks with less than 1000 cases reported a higher CFR rate compared to those with more cases.Conclusion: The study has revealed a considerably high CFR caused by the recurrent EVD outbreaks in Africa. It also notes an implementation gap of the prevention and control strategies, and thus identifies a need to strengthen the surveillance systems and response mechanisms to enable early detection and prompt control of future outbreaks.

scholarly journals Development of Pandemic Vaccines: ERVEBO Case Study

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 190
Author(s):  
Jayanthi Wolf ◽  
Risat Jannat ◽  
Sheri Dubey ◽  
Sean Troth ◽  
Matthew T. Onorato ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Development Program ◽  
Cost Effective ◽  
The United States ◽  
Public And Private ◽  
Ongoing Work ◽  
United States Food ◽  
Zaire Ebolavirus ◽  
States Food

Preventative vaccines are considered one of the most cost-effective and efficient means to contain outbreaks and prevent pandemics. However, the requirements to gain licensure and manufacture a vaccine for human use are complex, costly, and time-consuming. The 2013–2016 Ebola virus disease (EVD) outbreak was the largest EVD outbreak to date and the third Public Health Emergency of International Concern in history, so to prevent a pandemic, numerous partners from the public and private sectors combined efforts and resources to develop an investigational Zaire ebolavirus (EBOV) vaccine candidate (rVSVΔG-ZEBOV-GP) as quickly as possible. The rVSVΔG-ZEBOV-GP vaccine was approved as ERVEBOTM by the European Medicines Authority (EMA) and the United States Food and Drug Administration (FDA) in December 2019 after five years of development. This review describes the development program of this EBOV vaccine, summarizes what is known about safety, immunogenicity, and efficacy, describes ongoing work in the program, and highlights learnings applicable to the development of pandemic vaccines.

scholarly journals Analysis of Resistance of Ebola Virus Glycoprotein-Driven Entry Against MDL28170, An Inhibitor of Cysteine Cathepsins

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 192 ◽  
Author(s):  
Markus Hoffmann ◽  
Svenja Victoria Kaufmann ◽  
Carina Fischer ◽  
Wiebke Maurer ◽  
Anna-Sophie Moldenhauer ◽  
...  
Keyword(s):  
Viral Entry ◽  
Ebola Virus ◽  
Mutational Analysis ◽  
Cathepsin L ◽  
Cysteine Proteases ◽  
Host Cells ◽  
Single Amino Acid ◽  
Limited Information ◽  
Cysteine Cathepsins ◽  
Ebov Infection

Ebola virus (EBOV) infection can cause severe and frequently fatal disease in human patients. The EBOV glycoprotein (GP) mediates viral entry into host cells. For this, GP depends on priming by the pH-dependent endolysosomal cysteine proteases cathepsin B (CatB) and, to a lesser degree, cathepsin L (CatL), at least in most cell culture systems. However, there is limited information on whether and how EBOV-GP can acquire resistance to CatB/L inhibitors. Here, we addressed this question using replication-competent vesicular stomatitis virus bearing EBOV-GP. Five passages of this virus in the presence of the CatB/CatL inhibitor MDL28170 were sufficient to select resistant viral variants and sequencing revealed that all GP sequences contained a V37A mutation, which, in the context of native GP, is located in the base of the GP surface unit. In addition, some GP sequences harbored mutation S195R in the receptor-binding domain. Finally, mutational analysis demonstrated that V37A but not S195R conferred resistance against MDL28170 and other CatB/CatL inhibitors. Collectively, a single amino acid substitution in GP is sufficient to confer resistance against CatB/CatL inhibitors, suggesting that usage of CatB/CatL inhibitors for antiviral therapy may rapidly select for resistant viral variants.

scholarly journals Detection of Ebola Virus Antibodies in Fecal Samples of Great Apes in Gabon

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1347
Author(s):  
Illich M. Mombo ◽  
Matthieu Fritz ◽  
Pierre Becquart ◽  
Florian Liegeois ◽  
Eric Elguero ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Great Apes ◽  
Immunoglobulin M ◽  
Great Ape ◽  
Igg Antibodies ◽  
Exposure Risk ◽  
Fecal Samples ◽  
Specific Antibodies ◽  
Zaire Ebolavirus

Based on a large study conducted on wild great ape fecal samples collected in regions of Gabon where previous human outbreaks of Ebola virus disease have occurred between 1994 and 2002, we provide evidence for prevalence of Zaire ebolavirus (EBOV)-specific antibodies of 3.9% (immunoglobulin G (IgG)) and 3.5% (immunoglobulin M (IgM)) in chimpanzees and 8.8% (IgG) and 2.4% (IgM) in gorillas. Importantly, we observed a high local prevalence (31.2%) of anti-EBOV IgG antibodies in gorilla samples. This high local rate of positivity among wild great apes raises the question of a spatially and temporally localized increase in EBOV exposure risk and the role that can be played by these animals as sentinels of the virus’s spread or reemergence in a given area.

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