After being repeatedly “cue”, the not-so-new drug Remdesivir caught fire in early 2020. First into a number of medical experts, research institutions authoritatively issued the “potential to fight the new coronary pneumonia” drug candidate list, and then in the United States the first new coronary pneumonia patients appear in the “next day effect” of the bright performance, finally, Redsiewe officially entered the Wuhan anti-epidemic battlefield on February 5, jumped into the third phase of clinical trials.
It is said that it is a new drug, because Redcyway is not currently approved in any country in the world, it can be said that its safety and efficacy has not been scientifically conclusive.
It’s not new, too, because Redsiewe was tested as a new drug to fight the Ebola virus in 2018, and ended up being a disaster for two other competitors.
However, Redcieway’s remarkable broad-spectrum antiviral activity in a series of in vitro and animal experiments over the years still has good reason to be desired.
Gilead, the science firm behind Redsyway, said in an email to News beat on February 5 that Gilead had reached an agreement with the Chinese health authorities to provide drugs and support for two clinical trials, one of which assessed Redcieway for diagnosing an infection and had been hospitalized but showed significant clinical symptoms (e.g., The therapeutic effectiveness of patients who needed additional oxygen absorption, and another study assessed the efficacy of Redcivir for diagnosed patients with more severe clinical symptoms, such as the need for oxygen absorption.
Gilead has discovered the anti-flu virus “god drug” Tamiflu, this time, Redsiewe will be the next “Duffy”?
Gilead: Thirty years more
Gilead is not a household name for the pharmaceutical giant, but it has shown enough strength in the field of antivirals.
In 1987, the research and development biopharmaceutical company was founded in Foster, California. In order to avoid the forereach of large pharmaceutical companies, Gilead was soon after its creation was positioned to specialize in anti-viral new drugs to treat AIDS, viral hepatitis and other unsolved difficult diseases.
In 2001, Gilead’s first anti-AIDS drug, Viread, went on sale and remains one of the most widely used antiretroviral drugs. In 2013, Gilead launched solvadi, a hepatitis C drug that was hailed as the most heavily approved drug of the year.
In addition, Tamiflu, the anti-flu star drug, was first discovered by Gilead and was transferred to Roche at a later stage of the experiment.
In just 30 years, Gilead was one of the world’s top 10 pharmaceutical companies.
Redciewe’s own evolution reflects the long and tortuous nature of new drug research and development.
The breakthrough to Redsyway was a compound code-named GS-441524. This is a nucleoside analogue, a molecule that often appears pharmaceuticalally as a “competitive inhibitor”, i.e. “spoofing” the virus’s RNA polymerase binds to a “pretender” to disrupt the next replication of the virus.
As early as 2006, the Chung K Chu team at the University of Georgia in the United States reported the activity of a series of nucleoside analogues against the Severe Acute Respiratory Syndrome (SARS) virus, one of which is a compound 39 that is now a structural prototype of GS-441524. Although it can suppress the SARS virus, it is also toxic. Chung K Chu co-founder of Pharmasset was acquired by Gilead for $11 billion in 2011.
In a 2012 paper by Gilead researchers, GS-441524 was officially featured, demonstrating broad-spectrum antiviral capabilities, including hepatitis C, dengue fever, influenza, SARS, norovirus, and so on.
It is worth mentioning that The GS-441524 is currently being approved as a new cat infectious peritonitis drug, a once terminally ill feline disease that mutates from the cat coronavirus.
Incoming Ebola: Folding sand iron unsold
The development code-named GS-5734 was born with a further response from the GS-441524. It is worth noting that, since it is not currently available in any country in the world, Redciway is only the Chinese name of the compound and the unofficial drug name.
In March 2016, the U.S. Army Infectious Diseases Hospital and Gilead, as first and second units, published a paper in Nature, reporting on an experiment in the treatment of rhesus monkeys infected with ebola virus with Redciewe.
The paper says Redcivir is a small molecule antiviral drug, a precursor to adenine C-nucleoside nucleosomes. The so-called pre-drug, that is, a class of compounds obtained after chemical structural modification of the drug, in vitro inactive or less active, in the body by enzyme or non-enzyme conversion release of active drugs and play a efficacy.
In vitro studies have shown that Redcivir inhibits the replication of a variety of human RNA virus pathogens, including the Ebola virus (EBOV), respiratory syncytial virus (RSV), junining virus (JUNV), the salad fever virus (LASV), and the Middle East Respiratory Syndrome virus (MERS).
The results of the rhesus monkey experiment showed that treatment began three days after the virus was exposed (when 2 out of 6 monkeys had detected systemic viral RNA), a daily intravenous injection of 10 mg/kg of redsiewe, 12 consecutive days after the Ebola virus replication was significantly inhibited, the monkey survival rate was 100%, and clinical symptoms improved significantly.
However, Redsiewe failed to pass the clinical trial.
In November 2018, in response to the Ebola outbreak, congo (DRC) launched a clinical control trial at the initiative of WHO to test the efficacy of four new drugs, Remdesivir, MAb114, REGN-EB3 and Zmapp.
It took only nine months for the contest to be decided. Due to the clear lead of REGN-EB3 and mAb-114, the Committee decided in August 2019 to close the trial early and extend the two drugs on a wide scale.
Both drugs are “antibody cocktails”, a mixture of different antibodies.
mAb-114 is derived from a mixture of antibodies obtained from survivors of the 1995 Ebola outbreak, which were isolated years later by the U.S. National Institute of Allergy and Infectious Diseases. REGN-EB3, developed by Regeneron in New York, USA, is an antibody produced by the Ebola virus in mice with an “anthropomorphic” immune system.
Overall trial results for 499 patients showed that patients treated with mAb-114 and REGN-EB3 had mortality rates of 34% and 29%, respectively, while those treated with Redciwe and Zmapp had mortality rates of 53% and 49%, respectively.
For those who received treatment soon after infection and had low viral levels, the difference in efficacy of the new drug was more pronounced. Their mortality rates after treatment with mAb-114 and REGN-EB3 were as low as 11% and 6%, respectively, compared with 33% and 24% for Redsywe and Zmapp.
Ridsiwe withdrew from the fight against Ebola early. Clinical trial registration information shows that the Redsey wee trial was originally expected to end in 2023, the actual end date is September 2019.
Wuhan anti-epidemic: willow dark flowers and another village?
In the meantime, however, Gilead did not stop studying Redcie’s role in other areas, including coronaviruses, setting the stage for the comeback.
In 2018, Gilead published early results of Redcywe’s use of anti-coronavirus infection, showing that it can suppress SARS and MERS viruses in vitro.
Some researchers have thought of Redsiewe after the outbreak of the new coronavirus 2019-nCov outbreak.
The Ralph Baric team at the University of North Carolina recently published a mouse experiment on MERS, and Redsiewe was among those tested. The team believes Redciway’s effectiveness against MERS may be re-emerging on the coronavirus, Science reported on January 27. “For all the coronaviruses we tested, Redcivir is active, and I’m not surprised if it’s also active against emerging coronaviruses. Mark Denison, a coronavirus expert at Vanderbilt University, said.
On January 24, Lu Hongzhou, party secretary of the Shanghai Public Health Clinical Center, mentioned a number of potential drugs, including Redsiewe, and believed that from the current research data, Redsiewe is probably the most promising anti-new crown drug.
On January 25, the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences and the Institute of Immunochemistry of the Shanghai University of Science and Technology, a joint emergency response team against 2019-nCoV virus infection, screened 30 drugs with therapeutic potential, the sixth of which was Ridsywe.
On January 28, the Wuhan Institute of Viruses of the Chinese Academy of Sciences and the Institute of Toxic and Pharmaceutical Medicine of the Academy of Military Medical Sciences jointly announced the discovery of three existing drugs that have a better cell-level inhibition effect on new coronaviruses, including Ridsiewe.
But despite the frequent rosters of experts, it was a January 31 paper in the New England Journal of Medicine that documented the treatment of the first new coronavirus pneumonia patient in the United States. The patient received the Redsie vein on the 7th day of his stay, and the next day he had a fever and no longer needed oxygen absorption, leaving only dry cough and runny nose.
Gilead immediately issued a statement saying that Ridsiewe had not yet been approved for listing anywhere in the world and that its safety and effectiveness had not been proven. Weighing the pros and cons of using the experimental new drug at the request of the attending physician and with the support of local regulators, Gilead provided Redcie vir for a small number of patients with the new coronavirus pneumonia, which was used for critical care without any choice, which is what the clinic calls the “sympathetic drug” principle.
At the same time, Gilead announced that it had partnered with China for clinical trials. The latest news is that the drug arrived in China on February 4th and went directly into Phase III clinical trials.
The Redsiewe stock, originally produced in response to the Ebola outbreak, has finally come into use on the new crown battlefield.
In an emailed note to News beaten on February 5, Gilead said it was using part of Redciway’s inventory to meet the demand for “sympathetic medications” and the need for two clinical trials currently planned for China.
Gilead also said that while it has not yet been determined whether the drug can safely and effectively treat the new coronavirus infection, but in view of the urgency of the current situation, a variety of measures are being taken to speed up production progress and increase supply.
In the history of drug research and development, it is not uncommon for this disease to be developed and eventually used for each other’s cases. Redsey, of West Africa, is “back-light” or “bath-and-fire rebirth” in Wuhan this time, still waiting for scientific testing.
Yan Ning, a prominent structural biologist and professor at Princeton University in the United States, retweeted a “counter-tone” on Twitter on February 5th: “From several cases of survival or tragic death, there seems to be a particularly critical ‘deterioration’ … The case of cure in the United States is also given in the event of a sudden deterioration. Whether it’s a drug effect or a turning point, the only case at the moment, is not statistically significant, and it’s too early to say that Remdesivir is effective for the new crown. “