Jahnavi Sarma
... Read More
By clicking “Accept All Cookies”, you agree to the storing of cookies on your device to enhance site navigation, analyze site usage, and assist in our marketing efforts. Cookie Policy.
Written By: Jahnavi Sarma | Updated : August 10, 2021 10:01 AM IST
Image credits by: Remdesivir stops viruses from replicating themselves and imitates the actions of the building blocks of a virus' genetic material.
It's official. The third wave of the COVID-19 pandemic has hit the world and is likely to affect India too. Till date, to fight the COVID-19 virus, many existing drugs have been repurposed. The antiviral Remdesivir is one such drug that is currently used in the treatment of the viral disease that has taken the entire world hostage. Used in the treatment of Ebola and hepatitis C, this drug is also approved by the US Food and Drug Administration (FDA) for the treatment of adult and adolescent COVID-19 patients. In fact, this is the only FDA-approved antiviral for treatment of SARS-CoV-2 infection. Remdesivir stops viruses from replicating themselves and imitates the actions of the building blocks of a virus' genetic material. It is administered intravenously, a process that restricts its use to patients hospitalized with relatively severe or advanced cases of COVID-19. Now, researchers have strived to modify the current drug and create an oral version that can be taken earlier in COVID-19 diagnoses.
This was published in the online issue of Antimicrobial Agents and Chemotherapy recently where researchers from the 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.
According to the researchers, although vaccine development has had a major positive impact on the pandemic, the COVID-19 virus has continued to spread and cause disease -- especially among the unvaccinated. Now, with the evolution of more transmissible viral variants, breakthrough cases of COVID are being seen in different parts of the world. Researchers say that some of these variants can cause very severe disease in people with underlying conditions. Hence, there is an immediate need for an effective, well-tolerated antiviral drug that can be given to patents at high risk for severe disease at early stages of the illness.
For this to happen, researchers 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.
Researchers say that COVID-19 is a two-stage disease. According to them, 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 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. Researchers suspect that this complicated metabolism 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.
The researchers tested 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. They are confident that lipid prodrugs of this type, after further development, may reduce the severity of COVID-19 infections and reduce hospitalizations.
(With inputs from Agencies)
Disclaimer: The content on TheHealthSite.com is only for informational purposes. It is not at all professional medical advice. Always consult your doctor or a healthcare specialist for any questions regarding your health or a medical condition.