Posted on 08/03/2021 7:48:08 AM PDT by Red Badger
Remdesivir is an antiviral drug originally discovered as part of a program to develop antiviral agents with activity against novel emerging viruses. In the first months of the COVID-19 pandemic, it was tested as a potential therapeutic and found to measurably reduce recovery time for hospitalized COVID-19 patients. The Food and Drug Administration approved its use in October 2020 and it remains the only FDA-approved antiviral for treatment of SARS-CoV-2 infection.
Currently, Remdesivir must be administered intravenously, a process that restricts its use to patients hospitalized with relatively severe or advanced cases of COVID-19. The FDA has approved the use of Remdesivir only for adults and children age 12 and older.
In a new paper, published in the July 26, 2021 online issue of Antimicrobial Agents and Chemotherapy , researchers at University of California San Diego School of Medicine describe cell and animal studies that demonstrate how lipid modifications of Remdesivir nucleoside can improve drug delivery, effectiveness and toxicity compared to Remdesivir.
"Although vaccine development has had a major impact on the epidemic, COVID-19 has continued to spread and cause disease—especially among the unvaccinated," said co-first author Robert T. Schooley, MD, professor of medicine at UC San Diego School of Medicine. "With the evolution of more transmissible viral variants, breakthrough cases of COVID are being seen, some of which can be severe in those with underlying conditions. The need for effective, well-tolerated antiviral drugs that can be given to patents at high risk for severe disease at early stages of the illness remains high."
Senior author Karl Hostetler, MD, professor of medicine at UC San Diego School of Medicine, and colleagues synthesized three new lipid prodrugs, which combine a therapeutic agent (in this case, Remdesivir nucleoside) with one of several types of lipid-phosphates. The resulting conjugated molecule uses new pathways to enter cells: the lipid phosphate portion carrying along the drug.
The lipid phosphate prodrugs of the Remdesivir nucleoside can be taken orally, remaining intact and bioactive in the body following absorption from the digestive system.
"COVID-19 is a two-stage disease," said Schooley. "Rapid viral growth occurs shortly after infection and can trigger a misdirected immune response that results in an 'inflammatory' pneumonia in those who don't do well. In order to be maximally effective, antiviral therapy must be given early in the illness before the inflammatory phase of the illness results in hospitalization. These compounds are designed to be taken orally, rapidly absorbed from the gastrointestinal tract and to largely bypass the liver where most of Remdesivir's toxicity is seen."
To become active, Remdesivir requires modification by multiple enzymes. This complicated metabolism likely contributes to variable antiviral activity and toxicity in different cell types. For example, Remdesivir works well in lung cells, but is less effective in other organs and is relatively more toxic in hepatocytes (liver cells), which limits the amount of drug that can be administered to patients. In comparison, the lipid prodrugs described in the new paper are activated by a simple single enzymatic reaction and show a consistently potent antiviral activity and minimal toxicity across many cell types.
"An optimal antiviral for the treatment of SARS-CoV-2, and potentially other emerging viral infections, would be equally effective in any cell type that could be infected," said co-first author Aaron F. Carlin, MD, assistant professor of medicine and an infectious disease specialist at UC San Diego Health. "The metabolism of Remdesivir is complex, which may lead to variable antiviral activity in different cell types. In contrast, these lipid-modified compounds are designed to be activated in a simple uniform manner leading to consistent antiviral activity across many cell types."
The researchers assessed the lipid prodrugs in a variety of animal and human cell types and found that the lipid prodrugs uniformly inhibited SARS-CoV-2 RNA replication across cell types. They were well tolerated by hamsters, with levels of the drug remaining stable and persistent—a problem with current Remdesivir treatments.
"We believe that lipid prodrugs of this type after further development may reduce the severity of COVID-19 infections and reduce hospitalizations," said Hostetler.
Explore further
Neither remdesivir nor HCQ affect viral clearance in hospitalized patients with COVID-19
More information: Robert T. Schooley et al, Rethinking Remdesivir: Synthesis, Antiviral Activity and Pharmacokinetics of Oral Lipid Prodrugs, Antimicrobial Agents and Chemotherapy (2021).
DOI: 10.1128/AAC.01155-21
Journal information: Antimicrobial Agents and Chemotherapy
Money!!!
Not a surprise. The monoclonal are what changed game for my pts.
Remdesivir did not help my 94 yo MIL...but she was ripe for problems. Covid was only ONE of her health issues.
Ivermectin and Hydroxychloroquine have arguably more studies under their belt compared to Remdesivir, yet, it was Remdesivir that was approved ( very expensive treatment too ).
Remdesivir is a liver killer…I was worried when they gave it to Trump
“COVID-19 is a two-stage disease,” said Schooley. “Rapid viral growth occurs shortly after infection and can trigger a misdirected immune response that results in an ‘inflammatory’ pneumonia in those who don’t do well. In order to be maximally effective, antiviral therapy must be given early in the illness before the inflammatory phase of the illness results in hospitalization.”
About time the phrase “must be given early in the illness” starting showing up in discussions about treatments for COVID.
The drugs are used in conjunction with other substances to be effective. Just using the drug itself is not proper protocol.
I may be mistaken, but I think Trump received Regeneron, not Remdesivir.
In any case, people are different.
What works well for most patients might not work well for all.
Better docs have a lot of choices available to them rather than just a very few.
A good friend ended up in the local ICU in late February of last year/2020. He was in the hospital’s new super isolated ICU unit.
He was in the hospital for about 10 days. He was discharged in early March. The local ID knew about A and collected serum and other samples. Later all the tests failed to show any Covid. He had both gram positive and gram negative pneumonia in the collected specimens. This was before most of us knew anything about Covid 19.
Then again in the spring of this year, 2021, he was admitted to the same hospital and tested positive for Covid.
The local ID put him on Remdesivir and discharged him to home care 5 days later.
Since then my friend has been put on Eliquis, an oral blood thinner and had a Medtronic pacemaker installed.
He is still recovering and his energy is slowly coming back.
All of his blood tests show no active return of the Covid. He is self vaccinated with having the crud.
He is a widower and is living in an in law home on the property of a daughter. She is an RN and monitors him 24/7 with the eyes of a good RN and good questions. She was his home care RN re ivs and his meds.
Last week he played bridge with 3 of us old guys. My wife was there, and she did her RN scanning. She broke up the bridge group after about 3 hours and told him, as the RN, it was time to stop the bridge and to go home.
Which we did!:)
Condolences. Same situation with my 84yo father. By the time he was tested for COVID, he had probably had it for at least a week - pretty late to start any treatment.
Exactly
“Although vaccine development has had a major impact on the epidemic, COVID-19 has continued to spread and cause disease—especially among the unvaccinated,...”
nonsense. not proven assertion. stopped reading right there. doesn’t know what he’s taking about.
Asked my PCP yesterday about his protocol if I were to get sick. He said antibiotics and steroids to prevent pneumonia was number one. Remdesivir isn’t working as good as first thought. Ivermectin has its own issues. He said he wishes they would let them do more with the hydrochloriquin as that has the most studies conducted with the best results. He stressed a few times the pneumonia prevention as key.
“He stressed a few times the pneumonia prevention as key.” He is very right on that. Now here is a catch re current protocols. Being on a ventilator puts a person at risk for ventilator associated pneumonia and other infections. So it it very possible that the treatment ends up contributing to long term COVID based hospital stays if not death from COVID.
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