Connect with us

Health

Why is it so difficult to treat viral infections and how antiviral drugs such as the COVID-19 drug remdesivir work?

Published

on

 


Australian doctor Recently added another drug to their repertoire COVID-19 Treatment Example — A treatment that stimulates the body’s immune system to intercept and destroy the virus.

This drug, called sotrobimab, is an addition to several green-illuminated treatments, most of which help reduce inflammation caused by an overreaction of the immune system to the virus.

However, the only approved drug, remdesivir, stops the virus from rampaging in our cells. There, millions of copies of the virus are made and sent out to infect more cells and people.

So why is it so difficult to break the life cycle of viruses such as SARS-CoV-2 that cause COVID-19 disease?

Space to play or pause, M to mute, left and right arrows to seek, up and down arrows for volume.

Play audio.Time: 25 minutes 43 seconds

Can you learn from the past to treat this coronavirus? Listen to the friction of science.
download 35.3 MB

In a sense, COVID-19 is a two-stage disease, says Raymond Synagi, who develops antiviral drugs at Emory University.

In the first stages of the disease, the virus makes a copy of itself in the body, but often there are no symptoms.

Second, your body’s immune system works. For some people, when the immune system attacks an organ and causes inflammation, it progresses to a serious illness.

The idea of ​​treating the early stages of infection with antivirals is to prevent people from progressing to the point where a serious illness begins.

However, Remdesivir, the only direct-acting antiviral drug approved for use with COVID-19 in Australia, is not spectacular, says Sharon, an infectious disease researcher and director of the Doherty Institute. Lewin says.

“It gives you a little time, which may reduce your hospital stay and potentially bring a slight mortality benefit, but it’s not dramatic.”

Virology 101

A virus is, most basically, a series of genetic commands wrapped in a protein shell.

There are variations. Some have extra layers, such as the membrane around the shell. There are also several types of genetic code they can use. Some people have DNA like us, while others use a similar molecule called RNA.

But unlike bacteria that can survive and reproduce outside our bodies, viruses require hosts — they are not free-living organisms, says Gregory Moseley, a molecular virologist at Monash University. say.

This means that the virus cannot make or duplicate a copy of itself. To do this, you need to infect the host cell and order it.

Think of cells as a miniature factory. Different biological machines produce different cellular components.

When a virus invades it, it takes over, hijacks the biological mechanisms of the cell, reads the virus’s genetic instructions, and instead releases the virus’s components.

Four yellow circles with spikes and red center on blue background.
Electron micrograph of SARS-CoV-2 virus. It shows the peplomer that the virus uses to access the host cell.(((

Getty Images: narvikk

).

The virus bit is assembled into a new virus, leaving the cell and destroying it.

The fact that viruses use our cells for replication states that “in many cases it is actually very difficult to make a drug that targets the virus without simultaneously affecting the normal biology of our cells. Can be difficult, “says Dr. Moseley.

And until 70 years ago, few thought it was possible.

It starts with herpes …

The first antiviral drug was introduced by American pharmacologist William Prusoff in the 1950s, who was looking for a way to disrupt the life cycle of the herpes simplex virus.

An important aspect of the viral replication cycle is to make a copy of a unique genetic material from a genetic component and package it in a protective protein shell.

So Professor Prusov synthesized a drug that mimics one of these genetic components, but with a slightly different structure.

Older woman with short perm hair and white lab coat
Gertrude Elion shared the 1988 Nobel Prize in Physiology or Medicine for the use of innovative methods for developing new drugs.(((

Courtesy: GlaxoSmithKline plc GSK Heritage Archives

).

When a fake building block was incorporated into the viral genome building process, it prevented another building block from participating in it and stopped the operation (and viral replication).

It turned out to be an effective treatment for herpes keratitis, or herpes in the eye, laying the foundation for another American pharmacologist, Gertrude Elion, to develop the first successful antiviral drug, acyclovir. I did.

It is the active ingredient of herpes cream that can be purchased at pharmacies.

These nearly identical but incomplete gene building blocks, called nucleosides and nucleotide analogs, are behind many other antiviral drugs in use today, including remdesivir.

However, the development of antiviral agents actually began in the 1980s with the human immunodeficiency virus or HIV epidemic.

HIV’s “great success story”

HIV is a retrovirus — its genetic material is RNA, and when it infects a cell, it makes a DNA copy of its genome.

The DNA copy then slides into the host cell’s DNA, where it sleeps until activated, causing the cell to begin releasing the virus.

To make a copy of its DNA, HIV requires a biological machine called reverse transcriptase. Throwing a spanner with the help of reverse transcriptase can slow or stop the HIV virus in that pathway.

That’s what the first HIV drug treatment, azidotimidine or AZT, did. It was a nucleoside analog. A fake building block that works the same as those first herpes remedies.

However, it has side effects and the virus can quickly mutate and become resistant.

More classes of antiretroviral drugs followed. Some were small molecules that were literally incorporated into reverse transcriptase and stopped functioning, like a paper jam in a copier.

Two blue shabby shapes, one with yellow strands and the other with yellow pieces
Enzymes that help the HIV virus make a DNA copy of its genome are called reverse transcriptase (shown here in blue) and are shut down by drugs that mimic genetic components (left). , Pushed into the enzyme itself (right).(((

Getty Images: selvanegra

).

Others have prevented another enzyme, called a protease, from forming a shell of the virus.

Yet another target integrase, as the name implies, an enzyme that integrates a DNA copy of the viral genome into the DNA of a cell.

The real game changer was a combination therapy, says Professor Lewin.

And where HIV-infected people once had to take a handful of pills daily, today’s treatment consists of one pill taken daily to prevent infection if the virus wakes up from the incubation period. ..

“It was really a great success story of the last century,” says Professor Lewin.

Antiviral drugs can also prevent HIV infection. One of the two antivirals in the widely used pre-exposure prophylaxis Truvada was developed by Professor Schinazi’s team.

Two medicine bottles with Truvada on the label
Men who take the antiretroviral drug Tolvada daily significantly reduce their risk of becoming infected with HIV.(((

Getty Images: Justin Sullivan

).

Hit hard and hit quickly

For an antiviral agent to be effective, it must be very powerful, not only to leave healthy cells intact and target the virus, but also to quickly knock out almost the entire virus infection.

This is because viruses are replicated in huge numbers, and millions of new viruses can emerge in a matter of hours.

Some, such as RNA viruses, do not have a genetic “calibration.” That is, the genetic code can change or mutate very quickly, says Dr. Moseley.

Many viruses are also good at hiding from the body’s immune system.

Dr. Moseley’s lab investigates how the virus modifies the host cell to become an efficient virus factory and the tricks the virus uses to shut down the host cell’s immune defenses and improve replication and spread. I have.

Next, there are genome lurkers. Retroviruses such as HIV and herpes simplex virus that are hidden in our DNA.

The drug still can’t scrape HIV DNA from ourselves, but Professor Lewin’s lab at the Doherty Institute is looking for a cure to “wake up” the virus from the latent stage and remove it permanently.

That one big illness can Hepatitis C is cured by direct-acting antiviral agents.

Like HIV, it was discovered in the 1980s, but has no potential form.

Professor Schinazi and his fellow researchers have developed a treatment with a cure rate of almost 100 percent.

“There, we’re actually removing the virus from the liver and removing it completely,” said Professor Synagi.

“And basically … the virus is completely eradicated.”

So what does this mean for COVID-19?

SARS-CoV-2 also has no place to hide. It does not integrate that genetic code into ours.

However, for emergent viruses, the fastest way to find an effective treatment is to reuse drugs that have already been tried and tested for other illnesses.

This is not always a quick process, but it is faster than designing a drug from scratch.

“We can cut out a significant amount of R & D and proceed relatively quickly to efficacy and safety testing,” says Dr. Moseley.

“”[To repurpose an antiviral] It can take at least a few years.

“Therefore, it’s not quick, but it’s quick compared to the complete drug development pipeline.”

For example, remdesivir was originally developed for hepatitis C and later used for Ebola.

However, it has major drawbacks. Remdesivir courses usually include daily intravenous injections for a week or more, says Professor Schinazi.

The ideal COVID-19 antiviral drug is cheap and easy to manufacture and is given as a tablet to anyone as soon as the test result is positive or symptomatic, so the virus before initiating an immune hyperreactivity Can be crushed.

Professor Schinazi’s lab at Emory University is still looking for new and better antivirals to treat diseases such as HIV, but is also looking at COVID-19.

“We are moving forward, but not as fast as we want,” he says.

“I hope that antiviral drugs will be released soon next year or less.

..

Sources

1/ https://Google.com/

2/ https://www.abc.net.au/news/science/2021-09-12/covid-19-cure-drug-antiviral-hiv-treatment-remdesivir/100444818

The mention sources can contact us to remove/changing this article

What Are The Main Benefits Of Comparing Car Insurance Quotes Online

LOS ANGELES, CA / ACCESSWIRE / June 24, 2020, / Compare-autoinsurance.Org has launched a new blog post that presents the main benefits of comparing multiple car insurance quotes. For more info and free online quotes, please visit https://compare-autoinsurance.Org/the-advantages-of-comparing-prices-with-car-insurance-quotes-online/ The modern society has numerous technological advantages. One important advantage is the speed at which information is sent and received. With the help of the internet, the shopping habits of many persons have drastically changed. The car insurance industry hasn't remained untouched by these changes. On the internet, drivers can compare insurance prices and find out which sellers have the best offers. View photos The advantages of comparing online car insurance quotes are the following: Online quotes can be obtained from anywhere and at any time. Unlike physical insurance agencies, websites don't have a specific schedule and they are available at any time. Drivers that have busy working schedules, can compare quotes from anywhere and at any time, even at midnight. Multiple choices. Almost all insurance providers, no matter if they are well-known brands or just local insurers, have an online presence. Online quotes will allow policyholders the chance to discover multiple insurance companies and check their prices. Drivers are no longer required to get quotes from just a few known insurance companies. Also, local and regional insurers can provide lower insurance rates for the same services. Accurate insurance estimates. Online quotes can only be accurate if the customers provide accurate and real info about their car models and driving history. Lying about past driving incidents can make the price estimates to be lower, but when dealing with an insurance company lying to them is useless. Usually, insurance companies will do research about a potential customer before granting him coverage. Online quotes can be sorted easily. Although drivers are recommended to not choose a policy just based on its price, drivers can easily sort quotes by insurance price. Using brokerage websites will allow drivers to get quotes from multiple insurers, thus making the comparison faster and easier. For additional info, money-saving tips, and free car insurance quotes, visit https://compare-autoinsurance.Org/ Compare-autoinsurance.Org is an online provider of life, home, health, and auto insurance quotes. This website is unique because it does not simply stick to one kind of insurance provider, but brings the clients the best deals from many different online insurance carriers. In this way, clients have access to offers from multiple carriers all in one place: this website. On this site, customers have access to quotes for insurance plans from various agencies, such as local or nationwide agencies, brand names insurance companies, etc. "Online quotes can easily help drivers obtain better car insurance deals. All they have to do is to complete an online form with accurate and real info, then compare prices", said Russell Rabichev, Marketing Director of Internet Marketing Company. CONTACT: Company Name: Internet Marketing CompanyPerson for contact Name: Gurgu CPhone Number: (818) 359-3898Email: [email protected]: https://compare-autoinsurance.Org/ SOURCE: Compare-autoinsurance.Org View source version on accesswire.Com:https://www.Accesswire.Com/595055/What-Are-The-Main-Benefits-Of-Comparing-Car-Insurance-Quotes-Online View photos

ExBUlletin

to request, modification Contact us at Here or [email protected]