Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea

Sissoko, Daouda; Laouénan, Cédric; Folkesson, Elin; M’Lebing, Abdoul-Bing; Beavogui, Abdoul-Habib; Baize, Sylvain; Camara, Alseny-Modet; Maes, Piet; Shepherd, Susan; Danel, Christine; Carazo, Sara; Conde, Mamoudou N.; Gala, Jean‐Luc; Colin, Géraldine; Savini, Hélène; Boré, Joseph Akoi; Marcis, Fréderic Le; Koundouno, Fara Raymond; Petitjean, F.; Lamah, Marie-Claire; Diederich, Sandra; Tounkara, Alexis; Poelart, Geertrui; Berbain, Emmanuel; Dindart, Jean-Michel; Duraffour, Sophie; Lefevre, Annabelle; Leno, Tamba; Peyrouset, Olivier; Irenge, Léonid M.; Bangoura, N’Famara; Palich, Romain; Hinzmann, Julia; Kraus, Annette; Barry, Thierno Sadou; Berette, Sakoba; Bongono, André; Camara, Mohamed Seto; Munoz, Valérie Chanfreau; Doumbouya, Lanciné; Harouna, Souley; Kighoma, Patient Mumbere; Koundouno, Fara Roger; Lolamou, Réné; Loua, Cécé Moriba; Massala, Vincent; Kinda, Moumouni; Provost, Célia; Samake, Nenefing; Sekou, Conde; Soumah, Abdoulaye; Arnould, Isabelle; Komano, Michel Saa; Gustin, Lina; Berutto, Carlotta; Camara, Diarra; Camara, Fodé Saydou; Colpaert, Joliene; Delamou, Léontine; Jansson, Lennart; Kourouma, Etienne; Loua, Maurice; Malme, Kristian Nødtvedt; Manfrin, Emma; Maomou, André; Milinouno, Adele; Ombelet, Sien; Sidiboun, Aboubacar Youla; Verreckt, Isabelle; Yombouno, Pauline; Bocquin, Anne; Carbonnelle, Caroline; Carmoi, T.; Frange, Pierre; Mély, Stéphane; Nguyen, Vinh-Kim; Pannetier, Delphine; Taburet, Anne‐Marie; Tréluyer, Jean‐Marc; Kolié, Jacques Seraphin; Moh, Raoul; Gonzalez, Minerva Cervantes; Kuisma, Eeva; Liedigk, Britta; Ngabo, Didier; Rudolf, Martin; Thom, Ruth; Kerber, Romy; Gabriel, Marcin; Di, Antonino; Wölfel, Roman; Badir, Jamal; Bentahir, Mostafa; Deccache, Yann; Dumont, Catherine; Durant, Jean-François; Bakkouri, Karim El; Uwamahoro, Marie Gasasira; Smits, Benjamin; Toufik, Nora; Cauwenberghe, Stéphane Van; Ezzedine, Khaled; D’Ortenzio, Éric; Pizarro, Louis; Etienne, Aurélie; Guedj, Jérémie; Fizet, Alexandra; Fare, Eric Barte de Sainte; Murgue, Bernadette; Tran-Minh, Tuan; Rapp, C.; Piguet, Pascal; Poncin, Marc; Draguez, Bertrand; Duverger, Thierry Allaford; Barbe, Solenne; Baret, Guillaume; Defourny, Isabelle; Carroll, Miles W.; Raoul, Hervé; Augier, Augustin; Eholié, Serge; Yazdanpanah, Yazdan; Lévy-Marchal, Claire; Antierrens, Annick; Herp, Michel Van; Günther, Stephan; Lamballerie, Xavier de; Keïta, Sakoba; Mentré, France; Anglaret, Xavier; Malvy, Denis

doi:10.1371/journal.pmed.1002009

Cited by 17 publications

(11 citation statements)

References 1 publication

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“…No EBOV therapy has been approved yet even though some displayed good potential in the animal study (18,29,30). A clinical trial of small interfering RNA (siRNA)-based therapy (TKM-Ebola) was suspended because the results of interim analysis were not encouraging (31).…”

Section: Discussionmentioning

confidence: 99%

Novel Stable Ebola Virus Minigenome Replicon Reveals Remarkable Stability of the Viral Genome

Tao

Gan

Guo

et al. 2017

J Virol

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Ebola virus (EBOV) causes severe hemorrhagic fever in humans and other primates with a high case fatality rate. No approved drug or vaccine of EBOV is available, which necessitates better understanding of the virus life cycle. Studies on EBOV have been hampered because experimentations involving live virus are restricted to biosafety level 4 (BSL4) laboratories. The EBOV minigenome system has provided researchers with the opportunity to study EBOV under BSL2 conditions. Here, we developed a novel EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe the EBOV minigenome. The minigenomic RNA harboring a Gaussia luciferase and hygromycinresistant marker can replicate for months in a helper cell stably expressing viral nucleoprotein (NP), viral protein 35 (VP35), VP30, and L proteins. Quantification of viral RNA (vRNA), cRNA, and mRNA levels of the EBOV minigenome demonstrated that the stable EBOV replicon had much-more-active minigenome replication than previously developed transient-transfection-based EBOV minigenome systems, which recapitulate viral primary transcription more than genome replication. Interestingly, minigenome replication in the stable EBOV replicon cells was insensitive to interferon treatment or RNA interference. Moreover, RNase digestion of the replicon cell lysates revealed the remarkably stable nature of the EBOV minigenomic vRNA ribonucleoprotein complex, which may help improve understanding of EBOV persistence in convalescent patients. IMPORTANCEThe scope and severity of the recent Ebola outbreak in Western Africa justified a more comprehensive investigation of the causative risk group 4 agent Ebola virus (EBOV). Study of EBOV replication and antiviral development can be facilitated by developing a cell culture system that allows experimentation under biosafety level 2 conditions. Here, we developed a novel stable EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe the EBOV minigenome. The replicon system had more-active genome replication than previously developed transient-transfection-based EBOV minigenome systems, providing a convenient surrogate system to study EBOV replication. Furthermore, self-replicating minigenomic vRNA in the replicon cells displayed strong stability in response to interferon treatment, RNA silencing, and RNase digestion, which may provide an explanation for the persistence of EBOV in survivors.

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Section: Discussionmentioning

confidence: 99%

Novel Stable Ebola Virus Minigenome Replicon Reveals Remarkable Stability of the Viral Genome

Tao

Gan

Guo

et al. 2017

J Virol

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“…Moreover, it has been reported to be effective in animal studies of severe fever with thrombocytopenia syndrome virus, Bunyaviridae [78], West Nile virus [79], and Chikungunya virus [80]. Although it was used in the 2014 Western African epidemic of Ebola virus infection, the effects were inconsistent [81,82]. Regarding SARS-CoV-2, it was reported to inhibit viral infections at a relatively high half maximal effective concentration (EC 50 = 61.88 μM, selectivity index >6.46) [36].…”

Section: • Favipiravirmentioning

confidence: 99%

Interim Guidelines on Antiviral Therapy for COVID-19

et al. 2020

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cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.

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“…Favipiravir also showed an antiviral activity in experimental animals against other RNA viruses, including arenaviruses, alphaviruses, bunyaviruses, and flaviviruses [ 71 ]. Furthermore, preliminary results also indicated that favipiravir potentially possesses a moderate activity against Ebola [ 72 ]. Importantly, a recent nonrandomized, open-label study in patients ( n = 80) with non-severe COVID-19 showed that favipiravir (1600 mg orally twice daily on the first day, then 600 mg orally twice daily for thirteen days) with INF-α had significantly better therapeutic effects on SARS-CoV-2 infection, in terms of disease progression and viral clearance, than lopinavir/ritonavir with INF-α [ 73 ].…”

Section: Viral Polymerase Inhibitorsmentioning

confidence: 99%

Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

Al‐Horani

Kar

2020

Viruses

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The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.

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Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea

Cited by 17 publications

References 1 publication

Novel Stable Ebola Virus Minigenome Replicon Reveals Remarkable Stability of the Viral Genome

Novel Stable Ebola Virus Minigenome Replicon Reveals Remarkable Stability of the Viral Genome

Interim Guidelines on Antiviral Therapy for COVID-19

Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

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