GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses

Lo, Michael K.; Jordan, Robert; Arvey, Aaron; Sudhamsu, Jawahar; Shrivastava-Ranjan, Punya; Hotard, Anne L.; Flint, Mike; McMullan, Laura K.; Siegel, Dustin S.; Clarke, Michael O.; Mackman, Richard L.; Hui, Hon; Perron, Michel; Ray, Adrian S.; Cihlář, Tomáš; Nichol, Stuart T.; Spiropoulou, Christina F.

doi:10.1038/srep43395

Cited by 415 publications

(413 citation statements)

References 32 publications

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“…By the end of the West‐Africa EBOV outbreak, GS‐5734 clearly indicated 100% protection of rhesus monkeys following lethal EBOV challenge and an improved highly potent in vitro efficacy against Mayinga and Makona strains as compared to favipiravir . Moreover, GS‐5734 has been recently administered for the first time to a newborn baby .…”

Section: Introductionmentioning

confidence: 99%

Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

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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.

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Section: Introductionmentioning

confidence: 99%

Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

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“…When available, viral genomes modified with reporter genes can be used for cell-based luminescent or fluorescent screening of viral inhibitors (Beadle et al, 2016;Edwards et al, 2015;Fenaux et al, 2016;Feng et al, 2014;Lo et al, 2017;Madhvi et al, 2017;Wang et al, 2015c). This approach can be extended to screen inhibitors of other enzymes.…”

Section: Polymerasesmentioning

confidence: 99%

In vitro methods for testing antiviral drugs

Rumlová

Ruml

2018

Biotechnology Advances

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Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses.

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“…During the outbreak, her team screened a range of licensed therapeutic agents with the goal of repurposing them for treating Ebola, and also tested a large number of potential new antivirals. In a particularly successful effort, her group collaborated with researchers at Gilead Sciences to initially characterize and eventually demonstrate the effectiveness of the novel antiviral compound GS-5734 against Ebola virus (Lo et al, 2017) and they have since gone on to test it against lethal Nipah virus infection in nonhuman primates, in collaboration with Emmie de Wit and Heinz Feldmann at the NIH Rocky Mountain Laboratories. She closed her talk by referencing the recent development by the VSPB of high-throughput screening assays for antivirals against hemorrhagic fever viruses and other BSL-4 agents, and invited future collaborations with researchers who would like to test novel compounds, with the ultimate objective of finding clinical antiviral candidates.…”

Section: Emerging Virusesmentioning

confidence: 99%

Highlights of the 30th International Conference on Antiviral Research

et al. 2017

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The 30th International Conference on Antiviral Research (ICAR) was held in Atlanta, GA, USA from May 18 to 21, 2017. This report provides an account of award lectures, invited keynote addresses and oral presentations during the meeting. The 2017 Gertrude Elion Memorial Lecture Award by Michael Sofia highlighted one of the most important accomplishments in recent drug discovery in antiviral research, the identification of the hepatitis C virus direct-acting antiviral sofosbuvir and new alternatives to combat hepatitis B virus (HBV) infection. The Antonín Holý Lecture Award by David Chu on medicinal chemistry provided an overview of early developments of nucleoside analogs for the treatment of HIV and varicella zoster virus infection and how this knowledge serves to develop new drugs targeting HBV. Priscilla Yang gave the first ISAR Women in Science lecture. She reported on pharmacological validation of new antiviral targets for dengue, Zika and other flaviviruses. The William Prusoff Young Investigator Lecture Award by Maaike Everts described the Alabama Drug Discovery Alliance and the Antiviral Drug Discovery and Development Consortium, and how they are helping to accelerate the development of new antivirals. The 30th ICAR was a success in promoting new discoveries in antiviral drug development and research. The 31st ICAR will be held in Porto, Portugal, June 11-15, 2018.

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GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses

Cited by 415 publications

References 32 publications

Perspectives towards antiviral drug discovery against Ebola virus

Perspectives towards antiviral drug discovery against Ebola virus

In vitro methods for testing antiviral drugs

Highlights of the 30th International Conference on Antiviral Research

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