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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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Zee News
September 16, 2021
Zee News
The Goods and Service Tax (GST) Council is meeting on Friday (September 17) in Lucknow, Uttar Pradesh.
August 25, 2021
Hindustan Times
The effect of the coronavirus disease among children had been mostly mild and the severity much less than that in the adult population, said World Health Organization (WHO) chief scientist Dr Soumya Swaminthan, even as she stressed the importance of having a well-developed paediatric infrastructure. | Latest News India
August 24, 2021
Moneycontrol
'We may be entering some kind of stage of endemicity where there is low level transmission or moderate level transmission going on but we are not seeing the kinds of exponential growth and peaks that we saw a few months ago,' Swaminathan said.
Aman Sharma
August 11, 2021
News18
A top source said the government presently has 50 lakh vials of Remdesivir in stock and has plans for domestic production of Tocilizumab as well.
Sridhar Vivan
July 18, 2021
Bangalore Mirror
"No one expected that covid could hit us so hard. While many died at hospitals, there were hundreds who died on their way to hospital, a few hundreds died without beds, many at home waiting for ambul
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