|IUPAC Name:||2-ethylbutyl (2S)-2-[[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate|
Remdesivir(cas 1809249-37-3), also known as GS-5734, is an antiviral drug, a novel nucleotide analog prodrug. It was developed by Gilead Sciences as a treatment for filovirus infections such as Ebola virus disease and Marburg virus, though it has subsequently also been found to show reasonable antiviral activity against more distantly related viruses such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-coronavirus. GS-5734 was rapidly pushed through clinical trials due to the 2013–2016 West African Ebola virus epidemic crisis, eventually being used in at least one human patient despite its early development stage at the time. Preliminary results have been promising, and further clinical trials are planned.
Based on success against other coronavirus infections, Gilead provided remdesivir to physicians who treated an American patient in Snohomish County, Washington in 2020, infected with SARS-CoV-2 and is providing the compound to China to conduct a pair of trials in infected individuals with and without severe symptoms.
Originator: Gilead Sciences
Developer:China-Japan Friendship Hospital; Dr Reddys Laboratories; Gilead Sciences; INSERM; National Institute of Allergy and Infectious Diseases; NeuroActiva; Quantum Leap Healthcare Collaborative; Roche
Class:Adenine nucleotides; Amines; Antivirals; Esters; Furans; Nitriles; Phosphorus compounds; Pyridazines; Pyrroles; Small molecules; Triazines
Mechanism of ActionRNA: replicase inhibitors
Orphan Drug Status:No
New Molecular Entity: Yes
1. West J Emerg Med. 2020 May 20;21(4):737-741. doi: 10.5811/westjem.2020.5.47658.
Remdesivir for the Treatment of COVID-19: A Systematic Review of the Literature.
Musa A(1)(2), Pendi K(3), Hashemi A(4), Warbasse E(1), Kouyoumjian S(5), Yousif
J(1), Blodget E(6), Stevens S(1), Aly B(1), Baron DA(7).
(1)Wayne State University School of Medicine, Detroit, Michigan.
(2)Musa Biomedical Consulting, Anaheim, California.
(3)Southern California University of Health Sciences, School of Professional
Studies, Whittier, California.
(4)William Carey University, College of Osteopathic Medicine, Hattiesburg,
(5)Wayne State University School of Medicine, Department of Emergency Medicine,
(6)University of Southern California Keck School of Medicine, Division of
Infectious Diseases, Department of Medicine, Los Angeles, California.
(7)Western University of Health Sciences, Office of the Provost, Pomona,
In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a
global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over
200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given
that there is neither a vaccine nor proven treatment for COVID-19, there is
currently an urgent need for effective pharmacotherapy. To address the need for
an effective treatment of SARS-CoV-2 during the worldwide pandemic, this
systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an
anti-viral prodrug originally developed to treat Ebola virus disease, has shown
broad spectrum activity against the Coronavirus family. A recent case report
reported improvement of clinical symptoms with remdesivir in a patient with
COVID-19. After conducting a systematic search of 18 clinical trial registries
and three large scientific databases, we identified 86 potentially eligible
items. Following removal of duplicates (n = 21), eligible studies were reviewed
independently by two authors. After the first round of screening, inter-rater
agreement was 98.5% (κ = 0.925). After the second round of full-text screening,
inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical
trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We
identified the following primary outcomes: patients discharged (n = 2); time to
clinical status improvement (n = 2); improved O2 saturation (n = 2); body
temperature normalization (n = 2); and clinical status (n = 1). Secondary
outcomes in all identified studies included documentation of adverse events.
Phase 3 trials are expected to be completed between April 2020-2023. Therefore,
despite supportive data from in vitro and in vivo studies, the clinical
effectiveness of IV remdesivir for treatment of COVID-19 and potential side
effects remain incompletely defined in the human population.
2. Ann Intern Med. 2020 Oct 5. doi: 10.7326/M20-5752. Online ahead of print.
Remdesivir for Adults With COVID-19 : A Living Systematic Review for an American
College of Physicians Practice Points.
Wilt TJ(1), Kaka AS(2), MacDonald R(3), Greer N(3), Obley A(4), Duan-Porter
(1)Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and
Outcomes Research, and University of Minnesota School of Medicine, Minneapolis,
(2)Minneapolis VA Section of Infectious Diseases and University of Minnesota
School of Medicine, Minneapolis, Minnesota (A.S.K.).
(3)Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and
Outcomes Research, Minneapolis, Minnesota (R.M., N.G.).
(4)VA Portland Health Care System and Oregon Health & Science University School
of Medicine, Portland, Oregon (A.O.).
(5)Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and
Outcomes Research and University of Minnesota School of Medicine, Minneapolis,
BACKGROUND: Few treatments exist for coronavirus disease 2019 (COVID-19).
PURPOSE: To evaluate the effectiveness and harms of remdesivir for COVID-19.
DATA SOURCES: Several databases, tables of contents of journals, and U.S. Food
and Drug Administration and company websites were searched from 1 January
through 31 August 2020.
STUDY SELECTION: English-language, randomized trials of remdesivir treatments
for adults with suspected or confirmed COVID-19. New evidence will be
incorporated using living review methods.
DATA EXTRACTION: Single-reviewer abstraction and risk-of-bias assessment
verified by a second reviewer; GRADE (Grading of Recommendations Assessment,
Development and Evaluation) methods used for certainty-of-evidence assessments.
DATA SYNTHESIS: Four randomized trials were included. In adults with severe
COVID-19, remdesivir compared with placebo probably improves recovery by a large
amount (absolute risk difference [ARD] range, 7% to 10%) and may result in a
small reduction in mortality (ARD range, -4% to 1%) and a shorter time to
recovery or clinical improvement. Remdesivir may have little to no effect on
hospital length of stay. Remdesivir probably reduces serious adverse events by a
moderate amount (ARD range, -6% to -8%). Compared with a 10-day remdesivir
course, a 5-day course may reduce mortality, increase recovery or clinical
improvement by small to moderate amounts, reduce time to recovery, and reduce
serious adverse events among hospitalized patients not requiring mechanical
ventilation. Recovery due to remdesivir may not vary by age, sex, symptom
duration, or disease severity.
LIMITATIONS: Low-certainty evidence with few published trials, including 1
preliminary report and 2 open-label trials. Trials excluded pregnant women and
adults with severe kidney or liver disease.
CONCLUSION: In hospitalized adults with COVID-19, remdesivir probably improves
recovery and reduces serious adverse events and may reduce mortality and time to
clinical improvement. For adults not receiving mechanical ventilation or
extracorporeal membrane oxygenation, a 5-day course of remdesivir may provide
similar benefits to and fewer harms than a 10-day course.
PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health
Administration Office of Research and Development, Health Services Research and
Development Service, and Evidence Synthesis Program.
3. Clin Epidemiol Glob Health. 2020 Aug 7. doi: 10.1016/j.cegh.2020.07.011. Online
ahead of print.
Remdesivir and its antiviral activity against COVID-19: A systematic review.
Frediansyah A(1)(2), Nainu F(3), Dhama K(4), Mudatsir M(5)(6)(7), Harapan
(1)Research Division for Natural Product Technology (BPTBA), Indonesian
Institute of Sciences (LIPI), Wonosari, 55861, Indonesia.
(2)Department of Pharmaceutical Biology, Pharmaceutical Institute, University of
Tübingen, Tübingen, 72076, Germany.
(3)Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar, 90245,
(4)Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar,
Bareilly, 243122, Uttar Pradesh, India.
(5)Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda
Aceh, 23111, Indonesia.
(6)Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda
Aceh, 23111, Indonesia.
(7)Department of Microbiology, School of Medicine, Universitas Syiah Kuala,
Banda Aceh, 23111, Indonesia.
BACKGROUND: The aim of this study was to summarize the antiviral activities of
remdesivir against SARS-CoV-2, the causative agent of COVID-19.
METHODS: Available publications were systematically explored on some databases
and gray literature was examined. Publications were discussed narratively.
RESULTS: Remdesivir inhibits SARS-CoV-2 replication, reduces viral load, and
exerts protective effects in SARS-CoV-2 infected animals. Remdesivir also
reduces the pathological process, alleviates mild symptoms, and improves
pulmonary lesions in SARS-CoV-2-infecetd animals. Remdesivir has been used as a
compassionate drug for treating COVID-19 patients.
CONCLUSION: Although remdesivir has shown potent antiviral activities, more
efficacy assessments are urgently warranted in clinical trials.