Clinical Evaluation of Ebola Virus Disease Therapeutics

Liu, Guodong; Wong, Gary; Su, Shuo; Bi, Yang; Plummer, Frank; Gao, George F.; Kobinger, Gary P.; Qiu, Xiangguo

doi:10.1016/j.molmed.2017.07.002

Cited by 16 publications

(11 citation statements)

References 83 publications

(121 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the 2014‐2016 outbreak highlighted several therapeutic compounds that successfully crossed Phase I clinical trials, some of them indicated safety concerns . The clinical trials conducted during the outbreak lacked proper controls and statistical power due to the severity and urgency of the disease .…”

Section: Introductionmentioning

confidence: 99%

Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

View full text Add to dashboard Cite

Ebola virus disease (EVD), caused by Ebola viruses, resulted in more than 11 500 deaths according to a recent 2018 WHO report. With mortality rates up to 90%, it is nowadays one of the most deadly infectious diseases. However, no Food and Drug Administration‐approved Ebola drugs or vaccines are available yet with the mainstay of therapy being supportive care. The high fatality rate and absence of effective treatment or vaccination make Ebola virus a category‐A biothreat pathogen. Fortunately, a series of investigational countermeasures have been developed to control and prevent this global threat. This review summarizes the recent therapeutic advances and ongoing research progress from research and development to clinical trials in the development of small‐molecule antiviral drugs, small‐interference RNA molecules, phosphorodiamidate morpholino oligomers, full‐length monoclonal antibodies, and vaccines. Moreover, difficulties are highlighted in the search for effective countermeasures against EVD with additional focus on the interplay between available in silico prediction methods and their evidenced potential in antiviral drug discovery.

show abstract

Section: Introductionmentioning

confidence: 99%

Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…This is worsened by the high level of biocontainment (BSL-4) necessary for the manipulation of this virus that considerably hampers the development of antiviral drugs and vaccines. In this context, DR studies were prompted by the last outbreak (extensively reviewed in [30][31][32]). EBOV provides a unique example of a DR approach applied directly in clinical trials, as during the last outbreak several drugs were evaluated in infected patients (under both clinical trials and compassionate use) to test their ability to protect from lethal EBOV infection.…”

Section: Drug Repurposing For Rna Virus Infectionsmentioning

confidence: 99%

“…EBOV provides a unique example of a DR approach applied directly in clinical trials, as during the last outbreak several drugs were evaluated in infected patients (under both clinical trials and compassionate use) to test their ability to protect from lethal EBOV infection. These included the viral RNA polymerase inhibitors favipiravir (approved in Japan for the treatment of influenza A virus) [31,33], GS-5734 (an adenosine analog active against highly pathogenic coronaviruses) [34,35], and amodiaquine (an antimalarial drug widely used in Africa). Treatment of EBOV-infected patients with these drugs has been associated with a decrease in fatality rate compared to control patients [30]; however, their efficacy remains to be confirmed in randomized clinical studies.…”

Section: Drug Repurposing For Rna Virus Infectionsmentioning

confidence: 99%

Drug Repurposing for Viral Infectious Diseases: How Far Are We?

Mercorelli

Palù

Loregian

2018

Trends in Microbiology

213

188

View full text Add to dashboard Cite

Despite the recent advances in controlling some viral pathogens, most viral infections still lack specific treatment. Indeed, the need for effective therapeutic strategies to combat 'old', emergent, and re-emergent viruses is not paralleled by the approval of new antivirals. In the past years, drug repurposing combined with innovative approaches for drug validation, and with appropriate animal models, significantly contributed to the identification of new antiviral molecules and targets for therapeutic intervention. In this review, we describe the main strategies of drug repurposing in antiviral discovery, discuss the most promising candidates that could be repurposed to treat viral infections, and analyze the possible caveats of this trendy strategy of drug discovery.

show abstract

“…Furthermore, recent and ongoing EBOV outbreaks in the Democratic Republic of Congo (DRC) at the time of this writing, including the EBOV Ituri outbreak affecting over 3,000 individuals (CFR = 66%), emphasize the need for continued developments of therapeutics and vaccines [ 30 ]. The rVSV-EBOV-GP vaccine, which demonstrated great efficacy in nonhuman primates (NHPs) and humans [ 31 , 32 , 33 , 34 , 35 , 36 ], was approved in December 2019 after several phase III clinical and ring-vaccination trials demonstrated 100% protection in the absence of severe adverse events in over 10,000 individuals [ 37 , 38 , 39 , 40 , 41 , 42 ]. Additionally, over 200,000 doses were administered as part of compassionate use prior to FDA approval due to high efficacy and the 2018 outbreak in the DRC and Uganda ( Table 1 ) [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

To B or Not to B: Mechanisms of Protection Conferred by rVSV-EBOV-GP and the Roles of Innate and Adaptive Immunity

Pinski

Messaoudi

2020

Microorganisms

View full text Add to dashboard Cite

Zaire Ebola virus (EBOV) is a member of the Filoviridae family of negative sense, single-stranded RNA viruses. EBOV infection causes Ebola virus disease (EVD), characterized by coagulopathy, lymphopenia, and multi-organ failure, which can culminate in death. In 2019, the FDA approved the first vaccine against EBOV, a recombinant live-attenuated viral vector wherein the G protein of vesicular stomatitis virus is replaced with the glycoprotein (GP) of EBOV (rVSV-EBOV-GP, Ervebo® by Merck). This vaccine demonstrates high efficacy in nonhuman primates by providing prophylactic, rapid, and post-exposure protection. In humans, rVSV-EBOV-GP demonstrated 100% protection in several phase III clinical trials in over 10,000 individuals during the 2013–2016 West Africa epidemic. As of 2020, over 218,000 doses of rVSV-EBOV-GP have been administered to individuals with high risk of EBOV exposure. Despite licensure and robust preclinical studies, the mechanisms of rVSV-EBOV-GP-mediated protection are not fully understood. Such knowledge is crucial for understanding vaccine-mediated correlates of protection from EVD and to aid the further design and development of therapeutics against filoviruses. Here, we summarize the current literature regarding the host response to vaccination and EBOV exposure, and evidence regarding innate and adaptive immune mechanisms involved in rVSV-EBOV-GP-mediated protection, with a focus on the host transcriptional response. Current data strongly suggest a protective synergy between rapid innate and humoral immunity.

show abstract

Clinical Evaluation of Ebola Virus Disease Therapeutics

Cited by 16 publications

References 83 publications

Perspectives towards antiviral drug discovery against Ebola virus

Perspectives towards antiviral drug discovery against Ebola virus

Drug Repurposing for Viral Infectious Diseases: How Far Are We?

To B or Not to B: Mechanisms of Protection Conferred by rVSV-EBOV-GP and the Roles of Innate and Adaptive Immunity

Contact Info

Product

Resources

About