Development of experimental and early investigational drugs for the treatment of Ebola virus infections

Wong, Gary; Qiu, Xiangguo

doi:10.1517/13543784.2015.1052403

Cited by 7 publications

(5 citation statements)

References 95 publications

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“…In the first category is a product called TKM-100802, a small interfering ribonucleic acid that silences RNA replication by enzymatic cleavage of mRNA. TKM-100802 targets the L polymerase, viral protein VP24 and VP35 (26). In both guinea pig and non human primate challenge studies, this agent was found to offer protection (27 , 28).…”

Section: Role Of Experimental Therapeuticsmentioning

confidence: 99%

Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us

Varkey

Ribner

2016

Emerging Infections 10

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Section: Role Of Experimental Therapeuticsmentioning

confidence: 99%

Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us

Varkey

Ribner

2016

Emerging Infections 10

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Section: Role Of Experimental Therapeuticsmentioning

confidence: 99%

“…However, a post hoc analysis did suggest that favipiravir might be of benefit in patients presenting early in disease with lower viral loads (30). Other agents that have shown promise in in vitro or animal studies include GS-5734, BCX4430 and AVI7537 (18, 26). As these agents have not been evaluated in randomized human trials, their efficacy in humans is yet to be determined.…”

Section: Role Of Experimental Therapeuticsmentioning

confidence: 99%

Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us

Varkey

Ribner

2016

Microbiol Spectr

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Ending the West Africa Ebola virus disease (EVD) outbreak required an unprecedented international response. For the United States, participation in the international response to the West Africa EVD outbreak provided an opportunity to learn important lessons in four key domains critical to preparing for future outbreaks of EVD and other serious communicable diseases: (i) safe and effective patient care, (ii) the role of experimental therapeutics and vaccines, (iii) infection control, and (iv) hospital and community preparedness.

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“…EBOV-specific antibody levels are known to correlate statistically with survival from EVD (7). Monoclonal antibody (MAb)-based candidates, such as ZMAb (8, 9), ZMapp (10), and MIL-77 (11), are promising treatments (12–14), due to successes in the treatment and reversion of advanced EVD in humans and nonhuman primates (NHPs). In addition, ZMapp appears to have a beneficial effect on survival rates in clinical trials (15).…”

Section: Introductionmentioning

confidence: 99%

Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease

Wang

Wong

Zhu

et al. 2019

J Virol

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Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly and quantities are limited; therefore, MAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal F(ab′)2 fragments from horses hyperimmunized with an EBOV vaccine. The F(ab′)2 was found to potently neutralize West African and Central African EBOV in vitro. Treatment of nonhuman primates (NHPs) with seven doses of 100 mg/kg F(ab′)2 beginning 3 or 5 days postinfection (dpi) resulted in a 100% survival rate. Notably, NHPs for which treatment was initiated at 5 dpi were already highly viremic, with observable signs of EBOV disease, which demonstrated that F(ab′)2 was still effective as a therapeutic agent even in symptomatic subjects. These results show that F(ab′)2 should be advanced for clinical testing in preparation for future EBOV outbreaks and epidemics. IMPORTANCE EBOV is one of the deadliest viruses to humans. It has been over 40 years since EBOV was first reported, but no cure is available. Research breakthroughs over the past 5 years have shown that MAbs constitute an effective therapy for EBOV infections. However, MAbs are expensive and difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since EBOV is endemic in several third world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antiserum F(ab′)2 fragments from horses vaccinated with an EBOV vaccine, and we tested the protectiveness in monkeys. We showed that F(ab′)2 was effective in 100% of monkeys even after the animals were visibly ill with EBOV disease. Thus, F(ab′)2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.

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Development of experimental and early investigational drugs for the treatment of Ebola virus infections

Cited by 7 publications

References 95 publications

Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us

Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us

Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us

Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease

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