Remdesivir

Remdesivir

An antiviral drug candidate also known as GS-5734 developed by Gilead Sciences to treat Ebola virus that shows potential to treat coronavirus 2019-nCoV.

Remdesivir, also known as GS-7734, is a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-441524). Remdesivir is a drug candidate developed in 2017 by Gilead Sciences, in collaboration with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), University of California – San Diego and the Centers for Disease Control and Prevention (CDC). The drug was originally developed for treatment of Ebola infection, but in clinical trials it was found to be less effective than other treatments. Remdesivir has potential to treat coronavirus 2019-nCoV. Novel coronavirus (2019-nCoV) is closely related to severe acute respiratory syndrome Coronavirus (SARS-CoV).

Mechanism of action

Remdesivir is a Nuc inhibitor. Nuc inhibitors are nucleotide or nucleoside analogs that are incorporated into viral RNA or DNA in place of the nucleoside that is supposed to be there. Nuc inhibitors inhibit viral replication. They function as chain terminators, preventing the elongation of the RNA or DNA by constraining the conformation or hindering linkage with an incoming nucleotide. Remdesivir is a monophosphoramidate prodrug, of the C-adenosine nucleoside analogue GS-441524. Remdesivir metabolizes to form an adenosine analog with potent activity against the Filoviridae, Paramyxoviridae, Pneumoviridae and Orthocoronavirinae RNA virus families. Remdesivir targets the viral RNA dependent RNA polymerase (RdRp).

Remdesivir (GS-5734) is a prodrug that is converted into the C-adenosine nucleoside analog GS-441524 (A).

Coronavirus
Novel coronovirus (2019-nCoV)/SARS-CoV-2 (COVID-19)

SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Previously SARS-CoV-2 was known as novel coronavirus (2019-nCoV), a previously unknown pathogen, causing pneumonia and related to SARS-CoV, that emerged in Wuhan, China in December, 2019. Chinese authorities reported 2835 cases in mainland China and 81 deaths and numerous other countries had confirmed cases of 2019-nCoV. Assessment of remdesivir by controlled trial is planned in partnership between Gilead Sciences and the Chinese health authorities. A placebo-controlled Phase II trial of remdesivir is planned at Friendship Hospital in Beijjing, China and has been set to enrol 270 patients with mild and moderate pneumonia caused by 2019-nCoV. In the absence of any approved treatment options, Gilead has offered remdesivir to a small number of patients with 2019-nCoV as emergency treatment. Remdesivir was given to the first American confirmed to be infected with 2019-nCoV. In 2020, Gilead announced partnerships with NIAID, the FDA, the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Department of Health and Human Services (HHS), the China CDC and National Medical Product Administration (NMPA), the World Health Organizatioin (WHO) and individual researchers and clinicians to help patients and communities fighting 2019-nCoV.

A February, 2020 report found that in human cultured cells infected with 2019-nCoV, remdesivir were found to be effective at controlling infection. Clinical trials for Remdesivir were initiated in partnership between Gilead Sciences and the China-Japan Friendship Hospital in Beijing and by the NIH in the U.S. Gilead has plans to begin two phase III clinical studies in Asian countries in March, 2020 to assess dosing for intravenous administration of remdesivir. The U.S. FDA accepted the investigational new drug (IND).

On April 29, 2020, NIAID released preliminary data from their study showing that patients that received remdesivir recovered faster (11 days) than patients that received placebo (15 days). Also on April 29, 2020, Gilead released data from their clinical study which showed that a five-day course and ten-day course of remdesivir showed similar rates of clinical improvement. The Gilead study did not include placebo controls. On the same day a study based in China was published in the Lancet which found that remdesivir did not significantly improve time to clinical improvement, mortality or time of clearance of virus compared with placebo. The China study enrolled more severe cases of COVID-19 than the NIAID study and had not been able to enroll as many patients as planned because of the decrease in cases in Wuhan.

Other types of coronovirus

Gilead reported that remdesivir showed in vitro and in vivo activity in animal models against MERS and SARS, which are coronaviruses with similar structure to 2019-nCoV. Remdesivir reduced virus titer in mice infected with Middle East Respiratory Syndrome Coronovirus (Mers)-CoV, improved lung tissue damage with effects better than in mice treated with Lopinavir/Ritonavir combined with interferon-beta. Remdesivir was shown to have antiviral activity against endemic human COVs, OC43 (HCoV-OC43) and 229E (HCoV-229E) with submicromolar EC50 values. The drug was also shown to be efficacious against porcine deltacoronavirus (PDCoV).

Ebola virus

Therapeutic efficacy of remdesivir was shown in non-human primates against Ebola virus. Remdesivir was one of the experimental Ebola treatments removed from the Pamoja Tulinde Maisha clinical trial. According to the NIH, Remdesivir and the other drug, ZMApp, were less effective at preventing death than the other two drugs studied which were mAb114 an REGN-EB3.

Timeline

May 4, 2020
Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment
April 29, 2020
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial (The Lancet)

"remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies"

February 25, 2020
NIH clinical trial of remdesivir to treat COVID-19 begins
January 31, 2020
Gilead Partnering with China on Trial of Remdesivir as Coronavirus Treatment
January 10, 2020
Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
February 14, 2017
Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses
March 2, 2016
Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys

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January 29, 2021
WebWire
In the treatment of SARS-CoV-2, the virus that causes COVID-19, antiviral drug remdesivir has emerged as a promising candidate. Remdesivir works by disrupting the virus's ability to replicate, but its exact mechanism has remained a mystery. Using advanced computational simulations, researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have revealed just how the drug works at the molecular level. They also found that two drugs that work in a similar...
December 16, 2020
clinicaltrials.gov
Remdesivir and Convalescent Plasma Therapy for Treatment of COVID-19 Infection in Nepal : A Registry Study - Full Text View.
December 1, 2020
clinicaltrials.gov
IFN-beta 1b and Remdesivir for COVID19 - Full Text View.
Alex Keown
November 20, 2020
BioSpace
The World Health Organization (WHO) recommends against using Gilead Sciences' remdesivir as a treatment for COVID-19.
Reuters and Erika Edwards
November 20, 2020
NBC News
What treatments work for coronavirus? The World Health Organization advised against using the antiviral remdesivir for hospitalized Covid-19 patients.
Alex Keown
November 19, 2020
BioSpace
The EUA for the combination of Olumiant and Remdesivir marks the first combination for COVID-19 greenlit in the U.S.
Sarah Boseley Health editor
November 20, 2020
the Guardian
Remdesivir is an intravenous antiviral made the US firm Gilead. Photograph: Zsolt Czeglédi/AP
Telegraph reporters
November 20, 2020
The Telegraph
After reviewing the evidence panel finds drug has no meaningful effect on death rates or other important outcomes for patients
Reuters
November 13, 2020
@bsindia
Debate continues to rage in the medical industry about which drugs are best to treat Covid-19 patients
October 22, 2020
clinicaltrials.gov
Antiviral Activity and Safety of Remdesivir in Bangladeshi Patients With Severe Coronavirus Disease (COVID-19) - Full Text View.
October 28, 2020
clinicaltrials.gov
Treat COVID-19 Patients With Regadenoson - Full Text View.
IANS
August 7, 2020
@bsindia
Goas Health Ministry received 1,008 vials of Remdesivir from pharma major Cipla
Prem Anand Murugan | The Wire
July 16, 2020
@bsindia
Remdesivir costs around Rs 5,000 per vial with a total treatment cost in the range of Rs 35,000-50,000
Press Trust of India
July 15, 2020
@bsindia
The drug needs to be administered intravenously in a hospital, critical care setting, under the supervision of a registered medical practitioner
Ankur Banerjee| Reuters
July 10, 2020
@bsindia
The company, which had initially released the data from the trial in April, said the finding requires confirmation in clinical trials
Press Trust of India
July 9, 2020
@bsindia
Rajesh Bhushan, the Officer on Special Duty, Union Health Ministry, told an online media briefing Thursday that it has been noticed that certain drugs are not available freely in the market
Reuters
July 8, 2020
@bsindia
The drug will be available through the government and hospitals only, the company said
Press Trust of India
June 26, 2020
@bsindia
The drugs are costly so the state has decided to buy them itself
Press Trust of India
June 24, 2020
@bsindia
One set would be immediately supplied to Hyderabad, Delhi, Gujarat, Tamil Nadu, Mumbai and other parts of Maharashtra
Press Trust of India
June 22, 2020
@bsindia
Glenmark Pharmaceuticals has launched the antiviral drug Favipiravir, while Cipla and Hetero have received approvals from the Drug Controller General of India to launch Remdesivir
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