Antiviral therapeutics for the treatment of Ebola virus infection

Cardile, Anthony P.; Downey, Lydia G; Wiseman, Perry; Warren, Travis K.; Bavari, Sina

doi:10.1016/j.coph.2016.08.016

Cited by 15 publications

(9 citation statements)

References 30 publications

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“…During the 2014 to 2016 EBOV outbreak, the safety and efficacy of several therapeutic and prophylactic countermeasures were clinically evaluated (2). Although the protective efficacy of the vesicular stomatitis virus (VSV) vaccine was clinically demonstrated (3), statistically significant survival benefits are yet to be demonstrated by any therapeutic efficacy trials (4, 5). Understanding the immune properties specific to surviving or succumbing to an EBOV infection is important for the optimization of therapeutic products.…”

Section: Introductionmentioning

confidence: 99%

NK Cells Accumulate in Infected Tissues and Contribute to Pathogenicity of Ebola Virus in Mice

Fausther-Bovendo

Qiu

et al. 2019

J Virol

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Understanding the immune parameters responsible for survival following Ebola virus (EBOV) infection is paramount for developing countermeasures. In lethal EBOV infections, levels of both NK and T cells decline drastically in the circulation and lymphoid tissues before death. However, the fate of these lymphocytes in viral replication sites remains unknown. In this study, reverse transcription-PCR (RT-PCR) and fluorescence-activated cell sorting (FACS) analysis were used to investigate lymphocyte frequencies in various infected mouse tissues after challenge with mouse-adapted EBOV (MA-EBOV). A decrease in NK cell numbers from systemic circulation was observed concomitant to an increase of these cells in tissues that are supporting active replication of EBOV. Unexpectedly, NK accumulation in virus replication sites correlated with enhanced EBOV disease progression in specific conditions; at a high challenge dose, NK-depleted mice displayed lower viremia and liver damage and higher hepatic T cell levels. Upregulation of UL16 binding protein 1 (ULBP-1) was detected in hepatic T cells, suggesting that NK cells participate in their elimination. Overall, this study supports the concept that NK cells accumulate in EBOV-infected tissues and can contribute to viral pathogenicity. IMPORTANCE Ebola virus (EBOV) outbreaks can claim numerous lives and also devastate the local health infrastructure, as well as the economy, of affected countries. Lethal EBOV infection has been documented to decrease the levels of several immune cells in the blood that are necessary to defend the host. This decrease in immune cells is, however, not observed in individuals who survive EBOV infection. Having a better grasp of how these immune cells are lost is therefore of high importance to develop and improve new and existing therapeutics. The significance of our research is in identifying the mechanism responsible for the apparent loss of immune cells in lethal EBOV infection. This will allow therapeutic options aimed at preventing the loss of these immune cells, therefore allowing infected individuals to better fight the infection.

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Section: Introductionmentioning

confidence: 99%

NK Cells Accumulate in Infected Tissues and Contribute to Pathogenicity of Ebola Virus in Mice

Fausther-Bovendo

Qiu

et al. 2019

J Virol

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“…Momentous leap has been witnessed toward the designing of efficacious EBOV drugs and therapeutics during the short span of only few years, even though the efficacy of several biologicals and vaccines were evaluated during the recent West African outbreak, it remained elusive to ratify a licensed EBOV disease treatment regimen ( 123 ).…”

Section: Advances In Developing Drugs and Therapies Against Ebovmentioning

confidence: 99%

Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus

et al. 2018

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Ebola virus (EBOV), a member of the family Filoviridae, is responsible for causing Ebola virus disease (EVD) (formerly named Ebola hemorrhagic fever). This is a severe, often fatal illness with mortality rates varying from 50 to 90% in humans. Although the virus and associated disease has been recognized since 1976, it was only when the recent outbreak of EBOV in 2014–2016 highlighted the danger and global impact of this virus, necessitating the need for coming up with the effective vaccines and drugs to counter its pandemic threat. Albeit no commercial vaccine is available so far against EBOV, a few vaccine candidates are under evaluation and clinical trials to assess their prophylactic efficacy. These include recombinant viral vector (recombinant vesicular stomatitis virus vector, chimpanzee adenovirus type 3-vector, and modified vaccinia Ankara virus), Ebola virus-like particles, virus-like replicon particles, DNA, and plant-based vaccines. Due to improvement in the field of genomics and proteomics, epitope-targeted vaccines have gained top priority. Correspondingly, several therapies have also been developed, including immunoglobulins against specific viral structures small cell-penetrating antibody fragments that target intracellular EBOV proteins. Small interfering RNAs and oligomer-mediated inhibition have also been verified for EVD treatment. Other treatment options include viral entry inhibitors, transfusion of convalescent blood/serum, neutralizing antibodies, and gene expression inhibitors. Repurposed drugs, which have proven safety profiles, can be adapted after high-throughput screening for efficacy and potency for EVD treatment. Herbal and other natural products are also being explored for EVD treatment. Further studies to better understand the pathogenesis and antigenic structures of the virus can help in developing an effective vaccine and identifying appropriate antiviral targets. This review presents the recent advances in designing and developing vaccines, drugs, and therapies to counter the EBOV threat.

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“… 113 ZMapp showed protective efficacy in a rhesus macaques challenge model. 113 However, a randomized, controlled human trial of ZMapp plus the current standard of care did not meet the statistical threshold set for improved efficacy as compared with the current standard of care alone (NCT02363322) 114 – 116 . Efforts to isolate potent neutralizing antibodies against Ebola are ongoing.…”

Section: Introductionmentioning

confidence: 99%

Antibody therapies for the prevention and treatment of viral infections

et al. 2017

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Antibodies are an important component in host immune responses to viral pathogens. Because of their unique maturation process, antibodies can evolve to be highly specific to viral antigens. Physicians and researchers have been relying on such high specificity in their quest to understand host–viral interaction and viral pathogenesis mechanisms and to find potential cures for viral infection and disease. With more than 60 recombinant monoclonal antibodies developed for human use in the last 20 years, monoclonal antibodies are now considered a viable therapeutic modality for infectious disease targets, including newly emerging viral pathogens such as Ebola representing heightened public health concerns, as well as pathogens that have long been known, such as human cytomegalovirus. Here, we summarize some recent advances in identification and characterization of monoclonal antibodies suitable as drug candidates for clinical evaluation, and review some promising candidates in the development pipeline.

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Antiviral therapeutics for the treatment of Ebola virus infection

Cited by 15 publications

References 30 publications

NK Cells Accumulate in Infected Tissues and Contribute to Pathogenicity of Ebola Virus in Mice

NK Cells Accumulate in Infected Tissues and Contribute to Pathogenicity of Ebola Virus in Mice

Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus

Antibody therapies for the prevention and treatment of viral infections

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