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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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June 9, 2021
NDTV.com
The Union Health Ministry has issued clinical guidelines for the treatment of Covid-positive children amid concerns that a possible third wave of the coronavirus infection may target those aged below 18.
June 9, 2021
NDTV.com
The Union Health Ministry has issued clinical guidelines for the treatment of Covid-positive children amid concerns that a possible third wave of the coronavirus infection may target those aged below 18.
Livemint
June 7, 2021
mint
Remdesivir should be provided by the hospitals and should not be procured from open retail markets, the advisory said.Every hospital needs to set up a special drug committee (SDC) to review the use of Remdesivir at the facility periodically
May 31, 2021
Deccan Chronicle
Top doctors and experts explain the reality
May 29, 2021
NDTV.com
India has ramped up the production of anti-viral drug Remdesivir - used in the treatment of Covid patients - from 33,000 vials per day on April 11 to 3.5 lakh vials a day, the government has said.
Staff Writer
May 24, 2021
mint
A total of 3,02,544 were discharged across the country in the same duration, taking the total number of recoveries to 2,37,28,011
BS Web Team
May 19, 2021
@bsindia
Remdesivir may soon be dropped from ICMRs Covid treatment protocol, as experts have questioned its effectiveness in Covid treatment.
May 19, 2021
@TIMESNOW
Ganga Ram hospital chairperson Dr DS Rana said that there is no evidence of anti-viral drug's effectiveness in treating COVID-19 patients.
Staff Writer
May 17, 2021
mint
The Union Health Secretary apprised in the meeting that the CoWIN platform is being made available in Hindi and 14 regional languages by next week
Special Correspondent
May 16, 2021
The Hindu
Hospitals will have to send representatives to collect. The Chief Minister also cautioned hospitals to procure the drug to use it only on eligible patients.
Ritika Handoo
May 14, 2021
Zee News
Once again the internet has come to the rescue of people, giving some breather amid tough times. On a lighter note, a video has gone viral on social media where a man, who s being interviewed, does a faux pas and calls Remdesivir - a broad-spectrum antiviral medication that is widely being used to
May 12, 2021
Moneycontrol
To help India battle COVID-19, foreign aid is pouring in. As the second wave of the pandemic continues to extract a hefty toll and leads to a crippling shortage of medical supplies, we track the assistance from the world over, and what more is soon expected to reach.
May 11, 2021
The Times of India
Nagpur: Anti-viral drugs like Remdesivir and Tocilizumab may have grabbed attention in the recent past, but leading physicians strongly recommend a co.
May 11, 2021
The Times of India
Nagpur: The anti-viral Remdesivir injection, that had been in short supply for the last few weeks, suddenly seems to have lost all demand with number .
May 7, 2021
Moneycontrol
To help India battle COVID-19, foreign aid is pouring in. As the second wave of the pandemic continues to extract a hefty toll and there is a crippling shortage of medical supplies, we track the assistance from the world over, and what more is soon expected.
Press Trust of India
May 7, 2021
@bsindia
Read more about Covid-19: Allocation of remdesivir made up to May 16, says Sadananda Gowda on Business Standard. To ensure smooth supply of remdesivir used in the treatment of COVID-19 across the country, the allocation of the antiviral drug to the states and union territories has been made up to May 16, Union Chemicals and Fertilisers Minister Sadananda Gowda
May 7, 2021
@TIMESNOW
The incident took place around 8.30 PM at Gwalior's Maharajpura airport during landing and the plane skidded off the runway a little, the SP said.
ANI
May 7, 2021
@bsindia
The Centre has decided to increase production of anti-viral drug Remdesivir and it will be provided to people at governments price, said Union Minister Nitin Gadkari on Thursday
May 5, 2021
The Times of India
India News: NEW DELHI: The Centre on Wednesday issued revised guidelines for home isolation of asymptomatic Covid-19 patients and those with mild symptoms.
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