An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).
Pasquale Pagliano,Carmine Sellitto,Giuliana Scarpati,Tiziana Ascione,Valeria Conti,Gianluigi Franci,Ornella Piazza,Amelia Filippelli +7 more
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In this article, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction.Abstract:
Introduction Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment. Areas covered In this review, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction. Expert opinion RDV is the most widely investigated antiviral drug for the treatment of COVID-19. This attention on RDV activity against SARS-CoV-2 is justified by promising in vitro studies, which demonstrated that RDV was able to suppress viral replication without significant toxicity. Such activity was confirmed by an investigation in an animal model and by the results of preliminary clinical investigations. Nevertheless, the efficacy of RDV in reducing mortality has not been clearly demonstrated.read more
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Structural insights into ribonucleoprotein dissociation by nucleocapsid protein interacting with non-structural protein 3 in SARS-CoV-2
TL;DR: In this article , a 2.6 Å crystal structure of the N-terminal domain (NTD) of the coronavirus nucleocapsid (N) protein in complex with the ubiquitin-like domain 1 (Ubl1) of Nsp3 was reported.
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Insight into designing of 2-pyridone derivatives for COVID-19 drug discovery - A computational study
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References
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Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.
Manli Wang,Ruiyuan Cao,Leike Zhang,Xing-Lou Yang,Jia Liu,Mingyue Xu,Zhengli Shi,Zhihong Hu,Wu Zhong,Gengfu Xiao +9 more
TL;DR: This study evaluated the antiviral efficiency of five FAD-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two well-known broad-spectrum antiviral drugs remdesivir and favipiravir against a clinical isolate of 2019-nCoV in vitro.
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Remdesivir for the Treatment of Covid-19 - Final Report.
John H. Beigel,Kay M. Tomashek,Lori E. Dodd,Aneesh K. Mehta,Barry S. Zingman,Andre C. Kalil,Elizabeth L. Hohmann,Helen Y. Chu,Annie Luetkemeyer,Susan Kline,Diego Lopez de Castilla,Robert W. Finberg,Kerry Dierberg,Victor F. Tapson,Lanny Hsieh,Thomas F. Patterson,Roger Paredes,Daniel A. Sweeney,William R. Short,Giota Touloumi,David Chien Lye,Norio Ohmagari,Myoung-don Oh,Guillermo M. Ruiz-Palacios,Thomas Benfield,Gerd Fätkenheuer,Mark G. Kortepeter,Robert L. Atmar,C. Buddy Creech,JD Lundgren,Abdel G. Babiker,Sarah Pett,James D. Neaton,Timothy Burgess,Tyler Bonnett,Michelle Green,Mat Makowski,Anu Osinusi,Seema U Nayak,H. Clifford Lane +39 more
TL;DR: The data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.
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First Case of 2019 Novel Coronavirus in the United States.
Michelle Holshue,Chas DeBolt,Scott Lindquist,Kathy H Lofy,John Wiesman,Hollianne Bruce,Christopher Spitters,Keith M. Marzilli Ericson,Sara Wilkerson,Ahmet Tural,George Diaz,Amanda C. Cohn,LeAnne Fox,Anita Patel,Susan I. Gerber,Lindsay Kim,Suxiang Tong,Xiaoyan Lu,Steve Lindstrom,Mark A. Pallansch,William C. Weldon,Holly M. Biggs,Timothy M. Uyeki,Satish K. Pillai +23 more
TL;DR: This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
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Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy.
TL;DR: Since then, the number of cases identified in Italy has rapidly increased, mainly in northern Italy, but all regions of the country have reported having patients with COVID-19, and Italy now has the second largest number of CO VID-19 cases and also has a very high case-fatality rate.
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Compassionate Use of Remdesivir for Patients with Severe Covid-19.
Jonathan Grein,Norio Ohmagari,Daniel Shin,George Diaz,Erika Asperges,Antonella Castagna,Torsten Feldt,Gary M. Green,Margaret L. Green,François-Xavier Lescure,Emanuele Nicastri,Rentaro Oda,Kikuo Yo,Eugenia Quiros-Roldan,Alex Studemeister,John Redinski,Seema Ahmed,Jorge Bernett,Daniel Chelliah,Danny Chen,Shingo Chihara,Stuart H. Cohen,Jennifer Cunningham,Antonella D’Arminio Monforte,Saad Ismail,Hideaki Kato,Giuseppe Lapadula,Erwan L’Her,Toshitaka Maeno,Sumit Majumder,Marco Massari,Marta Mora-Rillo,Yoshikazu Mutoh,Duc Nguyen,Ewa Verweij,Alexander Zoufaly,Anu Osinusi,Adam DeZure,Yang Zhao,Lijie Zhong,Anand Chokkalingam,Emon Elboudwarej,Laura Telep,Leighann Timbs,Ilana Henne,Scott Sellers,Huyen Cao,Susanna K. Tan,Lucinda Winterbourne,Polly Desai,Robertino Mera,Anuj Gaggar,Robert P. Myers,Diana M. Brainard,Richard Childs,Timothy Flanigan +55 more
TL;DR: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients, and Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesavir therapy.