- 1. Early History of the Remdesivir Antiviral Drug
- 2. Global COVID-19 Pandemic
Remdesivir (GS-5734), the investigational antiviral medication, was introduced by the Gilead Sciences, Inc. for the treatment of Marburg virus and Ebola viral infection. This nucleoside adenosine analog integrates into the nascent viral RNA chains and eventually causes premature cessation porn addiction .
About Remdesivir Drug
Remdesivir is one of the leading broad-spectrum antiviral drugs. It blocks the replication of viruses to slow down the spread of infection to healthy cells.
In other words, when the invading viral pathogens try to replicate within the cells, the drug acts as a barrier to block the replication process. It also prevents further spreading of the viruses to the healthy cells.
Since it imitates a ‘genetic building block’ with a tacked-on molecular group, the drug is also called nucleoside analog.
Early History of the Remdesivir Antiviral Drug
Remdesivir was discovered in the mid-2010s during research to find an antiviral drug to treat emerging viruses by a joint effort by the US government and Gilead Sciences.
Initially, Gilead’s goal was to monitor the impact of the drug on animals mainly infected with the Ebola virus. The compound was effective in inhibiting viruses in vitro preventing the spread of infections due to pneumo-viruses, filo-viruses, paramyxoviruses, and coronaviruses.
Subsequently, Gilead started the Phase 1 testing of the drug in 2015 after achieving success on animals and non-human primates (NHP).
Ebola Virus Treatment
Gilead conducted several clinical trials to test the effect of Remdesivir on Ebola viruses during the epidemic in West Africa during 2013-16.
During the initial screening regulated by the Centers forDisease Control and Prevention (CDC) scientists, the drug emerged as a strong antiviral agent for controlling Ebola virus infections.
The United States Army Medical Research Institute of Infectious Diseases (USAMRID) in October 2015 claimed that GS-5734 was successful in blocking Ebola infection in Rhesus Monkeys. Later, the drug was also given to people as part of the clinical trials to study the effect of the drug on viral infections on humans.
Although the drug seemed effective in treating ebola viral infections during the initial phase of the trials, the results during the subsequent phases were not satisfactory. The failure of the drug to prevent deaths in the Democratic Republic of Congo during the Phase 3 trials in 2017 was a major setback for the Gilead Sciences.
The poor success rate during the Phase 3 studies left Remdesivir with an uncertain future. Consequently, the drug did not receive approval by any standard authority for antiviral treatment.
However, the drug was also given to patients during the Ebola virus outbreak in Kivu in August 2018. However, due to the inefficiency of the drug to combat and stop the spread of the disease, the health officials in Congo opted for the monoclonal antibody treatment as a suitable alternative.
Nipah Virus Treatment
Discovered in Malaysia in 1999, the Nipah virus is generally carried by fruit bats. It is infectious disease causing encephalitis, brain inflammation, neurological complications, and disease in the respiratory system. The instance of Nipah viral infection in May 2018 in India resulted in the death of 90% of the affected patients.
GS-5734 was first tested on a group of 4 African green monkeys in Bangladesh by the team of scientists at Gilead and National Institute of Allergy and Infectious Diseases (NIAID). The US Centers for Disease Control and Prevention (CDC) provided pathology and laboratory serology support for the project.
In the test trial with two groups having 4 monkeys each, a lethal dose of Nipah virus was given to all the monkeys.
Thereafter, the scientists started an experiment with the broad-acting antiviral nucleoside prodrug after 24 hours of giving the Nipah virus inoculation.
One group received a single dose of intravenous IV Remdesivir every day for 12 days.
During 92 days, 14 samples were taken from the animals. 2 of the monkeys receiving Remdesivir suffered from mild respiratory disease and eventually recovered within 3 weeks. The other 2 monkeys were completely healthy without any symptoms of the ailment. All the 4 animals receiving GS-5734 stayed healthy during the entire research period.
The research reports suggested that the nucleoside prodrug Remdesivir is highly effective in treating Nipah virus infections in monkeys.
Global COVID-19 Pandemic
The reports of early confirmed cases of global pandemic COVID-19 came from Wuhan City, central China in December 2019. Infected by the then unidentified pathogen, the victims suffered from severe pneumonia.
Studies revealed that the pathogen causing the 2019-20 Coronavirus pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belonging to the Betacoronavirus Genus.
Scientists are yet to find the actual source of infection but linked the cases to the consumption of seafood. By the end of March 2020, the pandemic spread across the UK, Italy, Spain, France, the US, India, and several other countries.
Since COVID-19 is a new and unknown pathogen, there was an urgent need for antiviral agents to combat the crisis and provide immediate aid to infected patients.
Considering the urgency, medical teams worldwide decided to conduct clinical trials with existing antiviral drugs. Scientists imparted different antiviral medicines to batches of patients to monitor the efficiency of each in curing the 2019-nCoV infection.
Medical teams worldwide are conducting trials to cope with the disease and provide effective and faster relief to the patients suffering due to acute respiratory syndrome.
Remdesivir is yet to receive approval as a safe drug for coronavirus treatment in humans and animals. At present, various medical research institutes are recommending this nucleoside prodrug for 2019-nCoV treatment considering the positive impact of the drug in resisting the infection.
Remdesivir Inhibits COVID-19 RNA Inducing Premature Termination
A research report published at the International Journal of Research in Pharmaceutical Sciences revealed that Remdesivir effectively inhibits the SARS-CoV and MERS-CoV in the Human Airway Epithelial (HAE) cells at the early stages of replication.
However, 99% of the protease inhibitors in GS-5734 coalesce with the proteins molecules in the human body. The remaining 1% of the synthetic drug inhibits the RNA synthesis of viral pathogens inducing premature termination faster. This report also stated that Remdesivir is a broad-spectrum drug competent in inhibiting the CoV infections both in vitro and in vivo models.
The scientists also recommend conducting more clinical trials to study the effect of the Remdesivir antiviral agents CoV pathogens.
Remdesivir Inhibits 2019-nCoV Human Cell Line
The scientists at the Wuhan Institute of Virology and the National Virus Resource Center executed an experiment with five FDA approved drugs- Chloroquine, Ribavirin, Nitazoxanide, Penciclovir, and Nafamostat including two prominent broad-spectrum antiviral drugs- Remdesivir and Favipiravir.
The scientists observed that Remdesivir being an adenosine analog integrates the virus RNA chains causing premature termination. Since this drug is capable of functioning during the post virus entry stage, revealing its agreement with the nucleoside analog anti-viral mechanism.
The research data also revealed that the EC90 value of Remdesivir in Vero E6 Cells infected with COVID-19 was 1.76 µM. It shows that this broad-spectrum antiviral drug can give positive results in NHP.
The research team also conducted studies to see the effect of this drug on human cells. When tested on humans, the drug successfully inhibited the 2019-nCoV in human liver Huh-7 cell lines. The outcome of the research suggested that the Remdesivir compound is highly effective in controlling novel coronavirus infection in vitro.
During the entire period of the trial on human patients, scientists found Remdesivir effective in treating multiple diseases including SARS-CoV 2 with a satisfactory safety track record.
COVID-19 Patients Respond to Remdesivir Treatment
During the Phase-3 clinical trials, 113 patients with severe Coronavirus symptoms received Remdesivir infusions daily at the Chicago hospital. Most of the patients responded quickly to the nucleoside analogs and recovered within less than a week. However, there are reports of 2 deaths during the trial period.
Remdesivir nucleoside analog prodrug has not yet received FDA approval as medicine for coronavirus treatment. Despite this, the drug is now undergoing clinical trials for treating COVID-19 patients in the US, the UK, and China.
Remdesivir is a broad-acting antiviral prodrug with nucleoside analogs. During different clinical trials and experiments on animals, NHPs, and humans, the drug has been found effective in combating and resisting viral infection in vitro.
However, this antiviral medicine failed to prevent deaths during the Ebola virus epidemic in the Democratic Republic of Congo.
The slow rate of successful recovery during the Ebola infection outbreak in North Kivu also posed a challenge for the drug to receive approval as a standard antiviral drug.
Despite being highly effective in curing 2019-nCoV patients during a clinical trial, GS-5734 is yet to receive FDA approval. The scientists also recommended conducting more clinical trials to study the impact of this broad-spectrum drug on patients with varying ailments. This is necessary to find how well people with severe viral infections respond to the treatment under different health conditions.
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