Ebola Virus: Current and Future Perspectives - IngentaConnect

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Ebola Virus: Current and Future Perspectives Surender Singh Jadav1, Anoop Kumar1, Mohamed Jawed Ahsan2 and Venkatesan Jayaprakash1* 1

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India; 2Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Jaipur, Rajasthan 302 039, India Abstract: The present outbreak associated with Ebola disease in Western countries of the African continent which is believed to be one of the massive eruptions caused by the Ebola viral infections. In the present scenario ebola has been transmitted to the European and American regions through the travelers from wide spread countries like Guinea, Liberia, Sierra Leone and Nigeria. The viral disease is spreading through the contact in any form by the infected persons or patients and creating huge risks to the mortals. The symptoms related to ebola virus are often highly pathogenic; about 70-80% of death cases are reported due to critical hemorrhagic fever. Early in infection, ebola virus infects macrophages and endothelial cells. It mainly produces a Viral Protein 24 (eVP24) which prevents interferon-based signals which are important for destruction of viruses. How ebola virus manipulates the function of the immune system is still unclear. Due to lack of this knowledge, no approved treatment is available. In this review, we have tried to compile the epidemiology, pathogenesis and treatment of ebola virus infection. The promising ligands against ebola virus have been also discussed which will be helpful for researchers to design drugs for the treatment of ebola virus disease.

Keywords: Ebola virus, pathogenesis, treatment, vaccines, vp24 inhibitors. 1. INTRODUCTION The hemorrhagic fever associated with Ebola viral disease (EVD) in humans is caused by the infectious Ebola virus which belongs to Filoviridae family [1]. The reemergence in early months of the current year related to this virus was reported in Central Africa, and now it has drawn the major attention throughout the world by spreading to West Africa and Europe [2-4]. According to WHO, the death toll of related to the present infection is rising continuously, till date 1145 death cases among 2,127 infected persons have been reported [5]. Few suspicious cases of Ebola have been reported in metro cities of Indian subcontinent which are under investigation as they believed to transmit by the travelers from Africa. Five distinct types of Ebola viruses including Bundibugyo (BDBV), Zaire (EBOV), Reston (RESTV), Sudan (SUDV) and Tai forest ebola viruses (TAFV) have been reported till date. The current major outbreak is stated as one of the destructive reemergence of EBOV strain, attacking people along with physicians who are curing the patients [6, 7]. The Ebola virus spreads in humans through human to human either by straight contact or with biological fluid secretions, organs related to infected persons, animals and indirect contact through the contaminated areas [8]. The fruit eating bats were also reported as reservoir for the same [9]. The Ebola infection can cause illness within the early 48-72 hours and lasts days after the transmission [5]. The characterized symptoms of EVD infection includes immediate *Address correspondence to this author at the Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi835215, Jharkhand, India; Tel: +91-9470137264; E-mail: [email protected] 2212-3989/15 $58.00+.00

onset of fever, rashes, sore throat, headache, muscle pain followed by diarrhea and vomiting; [4] the consequences leads to improper functioning of the liver and kidneys [1012]. The traces of virus were up reported to 7-8 weeks in biological fluids like semen. The possibility of dangerous threats to clinicians due to infectious biological fluids delays the diagnosis which may lead to increase the mortality rate [13]. The popular tests ELISA, RTPCR are employed for the diagnosis of the disease [14]. The antiviral therapies for treatment of Ebola infections are still not available; the clinical drugs and vaccines to combat the virus are under progress [15, 16]. The immediate supportive treatment for the severely infected persons through administration of rehydration with electrolytes was prescribed [17]. 2. EPIDEMIOLOGY The first outbreak of Ebola fever was observed in African tropical countries i.e, Sudan and Zaire, the associated virus then first isolated in 1976 [1]. The detailed reported epidemic cases across the world are listed in Fig. 1. The reemergence of Ebola viral infections is currently ongoing in several African countries that include Zaire, Guinea, Liberia, Ivory Coast, Sierra Leone, Nigeria, South Sudan and South Africa [2, 18, 19] (Fig. 1 and 2). The challenge is unprecedented because these countries have worst physician–patient ratios and weak health services. Therefore, good quality care is essential to reduce the death rate. 3. PATHOGENESIS OF EBOLA VIRUS Ebola virus is a hostile pathogen which is responsible for sever hemorrhagic fever in mortals, having the incubation period ranging from 14 to 21 days [20]. The supportive care © 2015 Bentham Science Publishers

Ebola Virus: Current and Future Perspectives

Table 1.

Infectious Disorders – Drug Targets, 2015, Vol. 15, No. 1

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Current drugs under clinical trials.

S. No.

Drugs

Phase of trial

Mechanism of action

Current status

Place of trial

1

Favipiravir

Phase 2

Inhibits the RNA dependent RNA polymerase

Recruiting

Guinea

2

Best Supportive Care + Amiodarone

Phase 3

Inhibit filovirus cell entry

Not yet recruiting

Sierra Leone

3

Brincidofovir (BCV, CMX001)

Phase 2

Inhibitor of Ebola virus replication

Not open for participant recruitment

NA

4

BCX4430

Phase 1

NA

Recruiting

United Kingdom

Countires affected with Ebola virus & cases from 1976 to 2014 1400 1200 1000 800 600

Infected cases

400

Death ttoll ors Survivo

200 0

Source: CD DC, WHO Fig. (1). The list of countries reported with Ebola Virus infections.

3500

Eboola virus reported r ccases (19766-2014)

3450

3000 Infected casess

Death casses

2500 206 22 2000 1500 1000 500

680 0 445 185

50

13

0

0

0

0 V (SUDV) Bundibugyo B Zaire Ebola virus Sudan Virus virrus (EBOV)) (BDBV)

Restonn Virus (RESSTV)

Tai forest ebola viruses (TAFV)

Sourcce: CDC, WHO O

Fig. (2). The total number of reported cases with Ebola Virus infections.

is a must incase of persons suffering with severe symptoms like septic shock intern which lead to death [21]. Limited or no connectivity to the remote areas, experimental facilities to examine the exact cause, scarcity of information at cellular levels have made difficulties to understand the complete mechanisms related to its pathogenesis [22]. However, some

in vitro assays and experimental animal models suggested that the destructive virus infects the macrophages and endothelial cells [23-25]. This leads to the unfavorable triggering/activation and incontinent secretion of mediators related to the inflammation [26-29]. Almost all viral infections have the similar mechanism related to inflammatory mediators

22 Infectious Disorders – Drug Targets, 2015, Vol. 15, No. 1

Jadav et al.

which can be considered as an authentication of viral hemorrhagic fevers [25, 30, 31].

shown in (Fig. 3). This information may play a vital role in understanding the pathogenesis of Ebola and in devising the novel therapeutic strategies.

3.1. Immune System and Ebola Virus 3.2. Interferons and Ebola Virus

Dendritic cells (DC) act as a bridge between the innate and adaptive immune system. They function as an antigen presenting cells which are activated through the pathogen associated molecular patterns (PAMP) and recognized by pattern recognition receptors (PRRs), when they are present on the surface [32, 33]. The dendritic cells are often activated through the release of internal signals, interferons associated with viral affected cells or the necrotic cell death resulting in heat shock proteins [34]. The immune system was then triggered through the migration of the activated dendritic cells to lymph nodes to present the antigen to T cells to launch the immune response [22]. In the current context the Ebola virus manipulates the functions of the dendritic cells, resulting in failure to initiate or activate the adaptive immunity [29]. Another study also demonstrated that inhibition of dendritic cell maturation without influencing the cytokine results in the impairment of T-cell multiplication is caused by the ebola virus VP 35. The VP35 also inhibits the CD40, CD80, CD86 and MHC (major histocompatibility complex)-II expressions associated with virus stimulations [22]. Ebola VP35 attenuates the ability of dendritic cells to motivate the initialization of naïve T cells, which results in failure of adaptive immune response as

VP 35

One of the human body’s initial reactions to a viral infection is to develop and release signaling proteins known as interferons, which increase the immune system reaction against viruses [35]. To induce an effective immune response against viral infection, interferons should pass their signals to other cells which finally activate the genes within the nuclei of cells to push the immune reaction [36]. Ebola virus produce a Viral Protein 24 (eVP24) which prevents these interferon-based signals which are important for destruction of viruses [37]. 4. EBOLA VIRUS GENOME Genomic sequence of the Ebola virus was completely expressed. The viral genome is a single stranded negative polypeptide, which belongs to RNA Viruses which size around 18-19 kb and 80nm in diameter; it contains the seven essential proteins which include Nucleoprotein (NP), Viral polymerase complex protein 35 (VP35), Matrix (VP40), Glycoprotein (GP), Minor nucleoprotein (VP30), membrane associated protein (VP24) and Polymerase (L-protein) [38, 39]. NP protein is also termed as nucleocapsid protein,

APC

Ebola virus

(Monocytes, Dcs)

Alteration of MHC1 or MHC2 MHC 1 or 2

TNF , IL-6, 8 Immature DC’s

VP 35 Naïve T cell not able to recognize

Hemorrhagic fever

Inhibit Septic shock Activation of TH and TC cell not occur

Mature DC

Death IFN release inhibited Faliure of adaptive immune response

Fig. (3). Pathogenesis of ebola virus.


which encapsidates the viral RNA genome by interacting with VP30 and VP34 proteins [40, 41]. The VP35 protein, referred as polymerase cofactor, is reported several times as competitor/antagonist for interferons produced by host cells via interaction with host TBK1 and IKBKE, causes the prevention of phosphorylation which results in triggering of regulatory factor of interferon (IRF3), and thus eliminating the antiviral effect [36, 42-44]. It plays a significant role in viral replication via RNA synthesis [45]. The VP40 is one type of membrane-associated protein which enables the gathering of viral particles by assembly and budding [46]. GP is composed of two glycoproteins i.e, GP1 and GP2; the first one acts like viral entry mediator, promotes by interacting with liver & lymph node endothelial cells and dendritic cells and in turn, initiates the infection [47-49]. The GP2 protein was responsible for viral fusion; it allows the perforation of virus inside the host cell cytoplasm [50, 51]. The transcription activating protein VP30 is useful in the RNA synthesis, it protects the transcription process throughout the period [52]. The VP24 prevents the antiviral activity induced by host cells through the inhibition of the interferons [40, 53, 54]. The terminal L protein is RNA directed polymerase and also termed as Replicase/Transcriptase, it performs the both functions and directly involves in the replication of RNA genome [55]. The role of VP35 protein in viral life cycle was extensively studied and reported by few groups, [56] a few X-ray crystallographic structures related to VP35, VP40 and glycoprotein of Zaire Ebola virus strain (1976) with interferons and some small synthetic pyrrolidine derivatives are available [45, 57, 58]. The recent pyrrolidine inhibitors reported against Ebola virus VP35 protein are listed in (Fig. 4, 11a and 11b). 5. CURRENT AVAILABLE INHIBITORS 5.1. Ebola Viral Glycoprotein Inhibitors A few small synthetic glycoprotein inhibitors of Ebola virus were successfully designed and tested against the same, the promising molecules identified as small-molecule entry


23

inhibitor for filoviruses are listed here. The benzodiazepine analog among the following was found to be inhibiting both the strains that include EBOV and Marburg viruses (MARV). However, the exact binding mode of these analogs is lacks and has to be concluded [59] (Fig. 5). Adamantines of benzyl piperazine inhibitors were reported against the EboV infections. NPC1 is vital for the glycoprotein (GP) which leads to viral entry and causes infection. The present compounds bound to NPC1, restricts the glycoprotein which in turn can be targeted and may inhibit anti-viral agents particularly, viral entry inhibitors [60] (Fig. 6). 5.2. Antioxidant Molecules as Filovirus Inhibitors An effort to identify the plausible drug candidates against the EBOV and MARV viral strains using cell-based assays provided the compound named NSC62914, it was also found to be inhibiting VEEV, Lassa virus and Rift Valley fever viral strains. Moreover, the role of antioxidant, responsible for the efficacy of the NSC62914 against EBOV & MARV, was tested using in-vivo mouse model and it was found to have less potency and higher doses, leading to the toxicity [61] (Fig. 7). 5.3. Anti-Malarial Agents as Ebola Virus Infections Inhibitors The ideal strategy has been utilized to recognize suitable antiviral agents and a very small number of anti-malarial agents tested against various viruses. Furthermore, this approach led to get a fewer 3,9-dimethylquinolino[8,7h]quinoline-1,7-diamine derivatives with promising inhibitory properties against Zaire Ebola viral infections (ZEBOV) [62]. The compound FGI-106 provided the broad spectrum antiviral effect which was confirmed by the cell-based assays and mouse model experiments. The primary MOA studies hypothesized that it may interfere in the common processes where the virus utilizes and the detailed mechanism of action is still unclear [63]. The remaining Quniolines were reported

Fig. (4). Ebola RNA genome with available X-ray crystallographic structures.


Jadav et al. O

NO2

O O O

CN O2 N N

Cl

H N

OH

IC50 = 10 μM

IC50 = 7.5 μM

Cl

N

O

CN

NO2

O

N

IC50 = 10 μM

F F F

NH

N

N

Cl

N

H

F

N

N

N O

IC50 = 14.5 μM

IC50 = 10 μM

IC50 = 15 μM

O

F N

N

F

F

N N O

NO 2 IC50 = 22.6 μM

IC50 = 15.5 μM

Fig. (5). Ebola viral glycoprotein inhibitors. O N H

O

O

N

N

N H

N

N

O IC50 = 41 μM

IC50 = 1.6 μM COOMe

COOMe

O O

N N H

N O

IC50 = 130 nM

O O

N N H

N O

N3

IC50 = 1 μM

Fig. (6). Few Adamantanes as EboV infection inhibitors.

for their anti malarial activity along with prominent antiviral effects [62]. Rationale behind the current approaches yielded few more DAAC (Daizachrysene) derived anti-EBOV agents; the modification at alkyl chains dispensed the preeminent anti-viral activity [64]. The salt form of these derivatives increased the efficacy with less toxicity (Fig. 8).

HO

OH

OH NSC62914

Fig. (7). Antioxidant molecules as Filoviral inhibitors.

5.4. Protein Phosphatase Inhibitors as Ebola Viral VP30 Protein Inhibitors The role of viral VP 30 protein was clearly demonstrated by its function, transcription process in viral replication is relatively dependant on VP30. The protien phosphatases regulates the function of viral VP30 by phosphorylation of protein which leads to replication of genome [65]. The Protein Phosphatase inhibitors are blocks by interacting with viral VP30 by dephosphorylation, which creates hindrances in viral replication. Benzylidene derivatives of 1, 2, 3, 4tetrahydroanthracene-9-carboxylic acid and their esters were proven to be inhibit the viral VP30 protein by inhibition of PP1. The following list of compounds was reported as Ebola viral infection inhibitors, the IC50 values of the compounds were less than 10μM [66] (Fig. 9).



25

O N

HN N

N

HN N

N

NH

N

N

N

NH

N

N

HN

N

NH

N O

IC 50 = 2.5-5 μM

IC 50 = 5 μM

IC 50 = 5-10 μM

O N

HN N

N

N

N

NH

FGI-106 EC 50 = 100 nM

O N

HN

N HN

N

N

O

N

HN

N

O

N

O

N

NH

NH

N

O

N

HN

N

O .4HCl

NH N

O

IC 50 = 0.696 ± 0.13 μM

NH

N

O

O

IC 50 = 1.13 ± 0.28 μM

.6TFA

IC 50 = 12.98 ± 0.17 μM

Fig. (8). Ant malarial Quinines as Ebola virus inhibitors. O N H

O

O H 2N

N H

O

O N H

O

O

O N N

N

N

S N H

N N

O

N O2

O S

N

F

O O O

N H

O O

N H

O

O

O

NH O

N

N H

N S

N

O

OH

Fig. (9). Protein Phosphatase inhibitors as Ebola VP30 protein inhibitors.

5.5. VP35 Inhibitors as Promising anti-EboV Agents The effective viral VP35 protein was reported with its several functions, the primary vital role includes the VP35 associated pathogenecity, secondary function was known to be useful in the mRNA synthesis, and thus it finally became a constructive protein for the replication of genomic –ve sense RNA [36, 67, 68]. The detailed role of VP35 was described in viral pathogenesis. The structure based in-silico screening of a zinc database of 5 million datasets using VP35 as a template became the wealthy approach for identification of promising VP35 inhibitors. The resulting inhibitors were well accommodated on the active site of the VP35 and the resulting X-ray crystallographic structures for obtaining selective inhibitors. The both R, and S conformers of substituted pyrrole derivatives were found to be inhibiting the viral VP35 protein. The reported active site residues of VP35 protein include Lys222, Gln241, Lys248, Lys251 and Ile298. The visual examination of ligand receptor interactions of the following compounds which are reported earlier suggested that, pyrrolidine nucleus were well accommodated on the active site, the acid of phenyl acetic acid/ benzoic acid portion exhibited the H-bonding with Lys251 [45]. The carbonyl O of the benzoyl ring part was found to have H-bonding with Gln241. All the ligands were surrounded by the other active site resi-

dues; however, this approach opened the gates for the identification of further novel therapeutic agents against EboV infections (Fig. 10 and 11). 5.6. Nucleoside Analogs as Ebola Viral Inhibitors in Virus Infected Animals and Human Cells A fewer animal model studies i.e, mice and mouse model indicated that, pyrralo pyrmidine, imidazopyridine analogs or Deazapurines were exhibited the effective inhibition of EboV virus at lower mg/kg doses in infected animals. Moreover, the detailed studies on mechanism of action of these compounds were in progress [69]. The adenosine based nucleoside (BCX4430) was reported to be the first small synthetic nucleoside agent which protect the animals against the filoviral infections by inhibiting the function of RNA polymerases belongs to EboV virus. The compound BCX4430 was reported for its broad spectrum of antiviral properties against wide range of viruses [70-72]. Moreover, the effect of BCX4430 in human cell studies was stated the same i.e it may become promising lead molecule against destructive EboV and Marburg (MARV) infections [73]. Recently, Favipiravir (T-705) is being evaluated for its antiviral efficacy based on its successful usage in non human primates against the EboV infections [74, 75] (Fig. 12).


Jadav et al.

R N

O

R1 R2

HO O

Ligand

R

R1

COOH

R2

Cl

PDB ID

Cl

4IBC

Br Cl

COOH

4IBE

S Cl COOH

R-Conformers

O

4IBG

O Cl

COOH

F

O O

F

4IBI

F

COOH

4IBB

S R N

O

R1 R2

HO O

Ligand

R

R1

R2

PDB ID

Br

COOH

4IBD

S Br

Cl

COOH

4IBF

S

S S-Conformers

COOH

F

F

F

F

COOH

Cl

4IBJ

F

Cl O O

Fig. (10). VP35 protein inhibitors of Ebola virus.

F

4IBK

S



Fig. (11a). Ebola Viral Glycoprotein (2EBO).

Fig. (11b). Ebola VP35 protein along with an inhibitor.

NH2

H N

N

N HN

and to maintain the blood pressure. EBOV infection leads to abnormal coagulations by activating extrinsic pathways of coagulation. So, anticoagulants may play a protective role in EHF. A continuous intravenous drip of recombinant humanactivated protein C, a major component of the blood anticoagulation, protected 18% of rhesus monkeys from a lethal challenge. This has been currently a licensed treatment of sepsis [23]. Furthermore, with a recombinant inhibitor of VIIa/tissue factor in rhesus monkeys, increased the chances of survival in the Ebola virus infections increased [78]. These therapeutic approaches have all been shown to delay EHF fatalities by several days, which would give additional time for a potential post exposure treatment to be effective. Supplying the oxygen in case of breathing problems is suggested. The analgesic, and anti-inflammatory agents give relaxation from the pain and miscellaneous medications to cover the secondary infections [79-81]. The immunomodulators like interferon type 1 at higher doses did not increase the survival [35]. The earliest treatment after the infections lowers the death rate or increases the survival [13].

NH2

N

N

N

OH

HO

OH

HO O OH

OH IC500 = 2 μM

BCX4 4430

Fig. (12). Nucleoside analogs as Ebola viral inhibitors in animal models.

5.7. Anti-Hypertensive Agents as Experimental Filoviral Inhibitors Recently, clinically approved and marketed antihypertensive drugs have been tested for their ant-filoviral properties. The hypothetical mechanism of action of these drugs was suggested to be interfering with the cellular processes essential for the viral entry such as signal transduction. The drugs include verapamil, amiodarone and dronedarone which exhibited the dose-dependent inhibition of filoviruses, the exact role of these drugs in inhibition of filoviruses are still under investigation [76] (Fig. 13).

6.1. Experimental Drugs A number of promising drug molecules are under investigation. The selective estrogen receptor modulators includes Clomiphene and Toremifene drugs which inhibited the progress of Ebola virus in infected mice, these drugs are currently being used to treat the breast cancer and infertility [82]. Another promising drug which is under development phase is ZMapp. ZMapp is a biopharmaceutical drug comprising of three humanized monoclonal antibodies [72, 83].

6. TREATMENT AND PROMISING THERAPEUTICS For Ebola infections, is no specific treatment exists till date [77]. The supportive therapy for symptomatic conditions includes the administration of the electrolytes and balancing fluids to counter the infection mediated dehydration N(C 2 H5 )2

N N(C 2 H5 )2

I

N O

O

O

O C 3 H7

O Drodar one

I

O

S O

27

H N

N

O O

O

C 3 H7 O Amiodaron ne

Fig. (13). Anti-hypertensive agents as Filoviral inhibitors.

O

Verapamill


Jadav et al.

On 31 July 2014, this experimental agent was first administered in the virus infected humans during the present massive outburst occurred in Africa. The success ratio of the drug is being under process. So, it is too early to say whether ZMapp is effective, since it is still in an experimental stage and has not yet been tested in clinical trials for safety or effectiveness [84]. Other promising treatments are based on antisense technology. The history of preventing the RNA polymerase L protein of ZEBOV by interfering with RNA in non human primates is achieved by the TKM-Ebola (TKM100802) and is currently under clinical investigation (Phase I) [8]. Presently, researchers have begun to focus on inhibiting the Ebola virus directly. The efficacy of the pyrazine carboxamide derivative T-705 (favipiravir) against Zaire Ebola virus (EBOV) was investigated and found that T-705 successfully suppresses the replication of Zaire EBOV under in vivo and in vitro conditions. These ﬁndings suggest that T-705 may be a potential candidate for the treatment of EBOV infections [75]. A number of promising drugs are under clinical trials which are summarized in Table 1 [85]. 6.2. Currently FDA Approved Drugs The exact inhibitors of ebola virus are still under development. In order to combat the present dreadful situation caused by the pathogenic ebola virus and lack of suitable agents in any form have made the treatment difficult. So, Table 2.

under the expanded access program, FDA agency has recently endorsed a few drugs under experimental conditions. The Brincidofovir is an effective antiviral agent having a wide range of antiviral applications [86]. The combinations of the small interfering RNAs (TKM-Ebola) are developed to target a class of proteins which are responsible for the destructiveness of the virus [21]. The experimental monoclonal antibodies called Zmapp were being utilized for the treatment of the current outbreak in African continent [84]. 7. VACCINE DEVELOPMENT The development of virus like particles (VLP) against the HBV, HPV, Parvovirus, Norwalk virus, Rotavirus has provided the essential information regarding the success ratio. VLPs administration can stimulate the formation of counteracting antibodies and virus specific CD8+ T lymphocytes [15-17, 67, 87, 88]. Moreover, VLPs have the capability of stimulating the adaptive immune response which made them risk free and functional in clinical studies [35, 89, 90]. However, in case of ebola virus, the lack of information about interactions between host immune system and virus have made difficulties in vaccine development [91]. The experimental vaccines against ebola infections in human or non human primates are still not available and few DNA vaccines are currently being testing and under clinical trials which are summarized in Table 2 [85, 92]. Recently, two vaccines i.e, ChimpAdeno3 and rVSV have been tested for their efficacy against Ebov infections in non human primates; surprisingly, they exhibited 100% protection along

Current Vaccines under clinical trial.

S. No.

Vaccines

Phase of trial

Mechanism of action

Current status

Place of trial

1

Ebola DNA plasmid vaccine

Phase 1

Activation of immune response

Completed

Uganda

2

Ebola Adenovirus Vector Vaccine (Ad5-EBOV)

Phase 1


Recruiting

China

3

Recombinant Ebola Adenoviral Vector Vaccine

Phase 1


Completed

United States, Maryland

4

Ebola Chimpanzee Adenovirus Vector Vaccine (cAd3-EBO)

Phase 1


Recruiting

United States, Georgia

5

Prime-Boost VSV Ebola Vaccine

Phase 1


Recruiting


6

VSV Ebola Vaccine

Phase 1


Recruiting

United States, California

7

Ebola DNA Plasmid Vaccine

Phase 1


Completed


8

BPSC-1001 Vaccine

Phase 1


Recruiting


9

VSV-ZEBOV Vaccine

Phase 1 /2


Ongoing

Geneva, Switzerland

10

cAd3-EBOZ Vaccine

Phase 1/2


Recruiting

Switzerland

11

Heterologous Prime-Boost Ebola Vaccine (Ad26. ZEBOV)

Phase 1


Recruiting

United Kingdom

12

Convalescent Plasma

A Phase 1/2

Antigen Antibody reaction

Recruiting

Liberia

13

EBOV convalescent plasma containing antibodies to EBOV

Phase 1

Antigen Antibody reaction

Recruiting

United States, Georgia


with compromised immunity. However, the exact figures regarding safety and risk factors on humans are not provided yet [92].

Infectious Disorders – Drug Targets, 2015, Vol. 15, No. 1 [13] [14]

8. CONCLUSION The hemorrhagic fever associated with ebola virus is the major health risk factor of the current destructive outbreak in African continent which resulted in 80-90% mortality. The present outbreak started in the last year in West Africa and now it is spreading to Europe and America. The incidence of this disease is being increased continuously. Pathogenesis of ebola viral infection is still not cleared. So, no approved therapy is available for the treatment. However, FDA has approved three drugs for its treatment under the expanded access program. Presently, many promising molecules are under preclinical and clinical phase. Hopefully they will successfully pass all these phases and reach to public as early as possible, are suffering from this disease.

[15]

[16]

[17]

[18] [19]

CONFLICT OF INTEREST

[20]

The author(s) confirm that this article content has no conflict of interest.

[21] [22]

ACKNOWLEDGEMENTS Authors gratefully acknowledge the financial support provided by the UGC and DST under RGNF and INSPIRE of the fellowships.

[23]

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Received: October 04, 2014

Revised: February 05, 2015

Accepted: February 08, 2015

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