Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430

Warren, Travis K.; Wells, Jay; Panchal, Rekha G.; Stuthman, Kelly S.; Garza, Nicole L.; Tongeren, Sean A. Van; Liu, Dong; Retterer, Cary; Eaton, Brett; Pegoraro, Gianluca; Honnold, Shelley P.; Bantia, Shanta; Kotian, Pravin L.; Chen, Xilin; Taubenheim, Brian R.; Welch, Lisa S.; Minning, Dena M.; Babu, Y.S.; Sheridan, William; Bavari, Sina

doi:10.1038/nature13027

Cited by 529 publications

(595 citation statements)

References 30 publications

(29 reference statements)

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“…Although unexplained hemorrhage (such as bruising and bleeding), kidney and liver dysfunction, cardiovascular distress and hypovolemic shock may occur as well in more serious cases [3][4][5][6]. Although several compounds have been proposed to treat this pathogenic disease [7][8][9][10][11][12][13][14][15], neither approved antiviral drugs nor vaccines are available in the market right now, and most of the drugs that have been given for the Ebola patients only meant to reduce the current symptoms, not directly targeting the virus [16]. Moreover, the extortionate cost of the newly-developed, non-FDA-approved drug makes the Ebola treatment, especially in poverty areas such as Africa, render ineffective [17].…”

Section: Introductionmentioning

confidence: 99%

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Tambunan¹,

Nasution²

2017

AIP Conference Proceedings

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Sensitivity differences between microporous NaY and hierarchical ZSM-5 modified electrodes as ammonia gas sensor AIP Conference Proceedings 1862, 030081 (2017) Abstract. Ebola remains as one of the deadliest diseases in the world, with almost 29,000 cases were reported and kill 11,000 of them, and yet neither treatment nor vaccine that can combat this disease effectively. This disease is caused by ebolavirus (EBOV), a primary member of Filoviridae family. The life cycle of this virus has been operated by several key proteins, one of them is VP24 protein, which has been known for its crucial role in the transcription and replication of EBOV. Therefore, targeting VP24 protein can be a solution for treating this pathogenic disease. In this study, virtual screening of Indonesian natural products as EBOV VP24 inhibitor was performed. About 2,020 ligands from many sources, including HerbalDB database, were obtained and screened by using DataWarrior software to measure its molecular and pharmacological properties, resulting 301 ligands in the process. Then, the molecular docking simulation was performed to check the ligand's binding interaction and affinity with EBOV VP24 protein; this simulation was done by using MOE 2014.09 software. This study resulted that cycloartocarpin was the best ligand to inhibit the EBOV VP24 protein. Therefore, this ligand should be checked its stability through molecular dynamics simulation and performed in vitro test to verify its bioactivity against the EBOV VP24 protein.

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Section: Introductionmentioning

confidence: 99%

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Tambunan¹,

Nasution²

2017

AIP Conference Proceedings

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“…It has shown effectiveness in mice and monkeys infected by Ebola virus and Marburg virus, respectively. 70 Its use in NHPs obtained promising results, with a survival rate of 83% in monkeys infected with Ebola compared to the control group. 71 From December 2014 to December 2015 it was underwent evaluation in phase I clinical trials.…”

Section: Pathophysiology Clinical Manifestations and Diagnosismentioning

confidence: 99%

Ebola virus – from neglected threat to global emergency state

Pacheco¹,

Rodrigues

Lisboa

2016

Rev. Assoc. Med. Bras.

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Objective: This review aims to update knowledge about Ebola virus disease (EVD) and recent advances in its diagnosis, treatment and prevention. Method: A literature review was performed using the following databases: ISI Web of Knowledge, PubMed, IRIS, Scopus and the websites of the CDC and the WHO. Additionally, we have included articles and reports referenced in the basic literature search, and news that were considered relevant. Results: The Ebola virus, endemic in some parts of Africa, is responsible for a severe form of hemorrhagic fever in humans; bats are probably its natural reservoir. It is an extremely virulent virus and easily transmitted by bodily fluids. EVD's complex pathophysiology, characterized by immunosuppression as well as stimulation of an intense inflammatory response, results in a syndrome similar to septic shock. The diagnosis is difficult due to the initial symptoms that mimic other diseases. Despite the high mortality rates that can amount to 90%, a prophylaxis (chemical or vaccine) or effective treatment does not exist. Two vaccines and experimental therapies are being developed for the prevention and treatment of EVD. Conclusion: Although the virus is known for about 40 years, the lack of knowledge obtained and the disinterest of government authorities in the countries involved justify the state of emergency currently exists regarding this infectious agent. Only the coordination of multiple entities and the effective commitment of the international community will facilitate the control and effective prevention of EVD.

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“…Others are FDA-Approved selective estrogen receptor modulators, SERMs (Clomiphene and toremifene) which inhibit EBOV. Recent studies have shown promise for a combination of monoclonal antibodies and for a small interfering RNA compound (BCX4430) as post exposure prophylaxis in non human primates (Warren et al, 2014). Key components of two of the most efficacious mAbs cocktails, titled MB-003 (MappBio) including antibodies c13C6, h13F6, and c6D8 and ZMAb (Defyrus) including antibodies c1H3, c2G4, and c4G7 have been recently combined and are in development for human use as a cocktail named ZMApp.…”

Section: No Vaccines or Therapeutics Are Yet Approved For Human Treatmentioning

confidence: 99%

THE STRENGTHS, WEAKNESSES, OPPORTUNITIES, AND THREATS (SWOTs) ANALYSES OF THE EBOLA VIRUS

Babalola

2016

AJID

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Background: Owing to the extreme virulence and case fatality rate of ebola virus disease (EVD), there had been so much furore, panic and public health emergency about the possible pandemic from the recent West African outbreak of the disease, with attendant handful research, both in the past and most recently. The magnitude of the epidemic of ebola virus disease has prompted global interest and urgency in the discovery of measures to mitigate the impact of the disease. Researchers in the academia and the industry were pressured to only focus on the development of effective and safe ebola virus vaccines, without consideration of the other aspects to this virus, which may influence the success or otherwise of a potential vaccine. The objective of this review was to adopt the SWOT concept to elucidate the biological Strengths, Weaknesses, Opportunities, and Threats to Ebola virus as a pathogen, with a view to understanding and devising holistic strategies at combating and overcoming the scourge of EVD. Method: This systematic review and narrative synthesis utilized Medline, PubMed, Google and other databases to select about 150 publications on ebola and ebola virus disease using text word searches to generate the specific terms. Relevant publications were reviewed and compared, findings were synthesized using a narrative method and summarized qualitatively. Results: Some of the identified strengths of ebola virus include: Ebola virus is an RNA virus with inherent capability to mutate, reassort and recombine to generate mutant or reassortant virulent strains; Ebola virus has a broad cellular tropism; Natural Reservoir of ebola virus is unconfirmed but fruit bats, arthropods, and plants are hypothesized; Ebola virus primarily targets and selectively destroys the immune system; Ebola viruses possess accessory proteins that inhibits the host' immune responses; Secreted glycoprotein (sGP), a truncated soluble protein that triggers immune activation and increased vascular permeability is uniquely associated with Ebola virus only; Ability to effectively cross the species barrier and establish productive infection in humans, non human primates, and other mammals; Ebola virus attacks every part of the human body; The Weaknesses include: Ebola virus transmission and persistence is severely limited by its virulence; Ebola virus essentially requires host encoded protein Niemann-Pick C1 (NPC1) for host's cell' entry; Ebola virus essentially requires host encoded proteins (TIM-1) for cell' entry; Relative abundance of Ebolavirus Nucleoprotein than the other virion components; The Opportunities harnessed by ebola virus include: Lack of infection control practices in African health-care facilities and paucity of health infrastructures, especially in the endemic zones; Permissiveness of circulating Monocytes, Macrophages and dendritic cells in virus mobilization and dissemination; Collection, consumption and trade of wild games (bushmeats); Pertubation and drastic changes in forest ecosystems present opportunities for Ebola...

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Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430

Cited by 529 publications

References 30 publications

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Ebola virus – from neglected threat to global emergency state

THE STRENGTHS, WEAKNESSES, OPPORTUNITIES, AND THREATS (SWOTs) ANALYSES OF THE EBOLA VIRUS

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