Existing FDA-approved medications can help fight COVID-19 disease. COVID-19 medications, previously approved by the US Food and Drug Administration.
USA (FDA), may promise to fight respiratory diseases caused by the SARS-CoV-2 coronavirus, according to a new modeling study by Northwestern Medical University of Texas. Center.
This scanning electron microscope image shows SARS-COV-2 (round gold objects) protruding from the surface of cells grown in the laboratory. The virus shown was isolated from an American patient.
“It can take months, even rapid approval, to develop new pharmaceutical agents that work against this virus,” said Professor Hashem Sadek, lead author of the study.
“That is why we see drugs that are already FDA approved, a strategy that has become increasingly popular in disease research.”
Most drugs exert their effects by binding to specific targets in the body or on disease-causing bacteria or viruses, connecting them to proteins, receptors, or channels to alter their function.
However, almost all drugs cause side effects due to off-target effects, which are associated with unexplained areas.
Professor Sadek and his colleagues argued that some FDA-approved medications may inadvertently target vulnerable parts of SARS-CoV-2.
To test this idea, they conducted a computer-based study to extensively investigate what drugs might be useful against this coronavirus.
They focused on the main protease (SARS-CoV-2 Mpro) of SARS-CoV-2, an enzyme used to bind long chains of viral proteins to host cells to self-replicate viruses. Direct and cut them into small pieces.
3D structure of the SARS-CoV-2 Mpro, in two different views. One protometer for the dimer is shown in light blue, the other in orange. Roman numerals are inscribed in the domain.
The amino acid residues of the catalytic site are indicated as yellow and blue spheres for Cys145 and His41, respectively. The asterisk marks a residue of protomer B (orange).
The black regions indicate the position of Ala 285 of each of the two III domains. The terms in the chain are labeled N and C for molecule A (light blue) and N * and C * for molecule B (orange).
“Scientists elsewhere have recently clarified the structure of this enzyme, including its binding pocket,” said Professor Sadek.
“A drug that binds tightly to this binding pocket can block its function, making the virus unable to multiply and spread the infection.”
To identify drug candidates, the researchers used a computer program to structurally unite all FDA drugs with binding pockets.
They then manually examined which drugs, which are structurally adjusted, could ever form strong chemical bonds with pockets inside.
Two-dimensional presentation of the coupling poses for the 11 main drug candidates. The blue arrows are hydrogen trunk bonds and the green arrows are side chain hydrogen bonds. Image courtesy of: Farag et al, doi: 10.26434 / chemrxiv.12003930.v1.
Unexpectedly, her main successes included several antiviral drugs, including darunavir, nalinavir, and saquinavir, which work by attacking proteases.
However, scientists have identified several candidates that are far from the use of antivirals. These included the ACE inhibitor Moexipril; The chemotherapeutic agents Daunorubicin and Mitoxantrone; Metamizole, a pain reliever; Bepotastine antihistamine; And antimalarial atovaquone.
One of the most promising candidates was rosuvastatin, a statin that is sold under the Crestor brand and is already being taken by millions of patients worldwide to lower cholesterol.
“Although many candidates are unlikely to be able to deliver critically ill patients, such as chemotherapeutic agents, rosuvastatin already exhibits a strong safety profile, is inexpensive, and is readily available,” said Professor Sadek.
“Because this study was conducted entirely by computer, it is unknown if any of these candidates would be truly active against SARS-CoV-2, and additional validation studies are required before any clinical application.”
But the study provides a starting point for other researchers to evaluate these drugs, both in the laboratory and in patients. Reassembling these FDA-approved drugs can be a quick method of treating patients who would otherwise have no choice.
The study is published on the prepress server ChemRxiv.org. Identification of FDA-approved drugs targeting the COVID-19 virus through structure-based drug repositioning.
Researchers Will Examine Library of Antiviral Drugs to Counter COVID-19. Scripps Research has announced that it will examine more than 14,000 compounds to see if there is any significant activity against COVID-19 for use in a therapy.
Scripps Research, USA The US has announced that its teams are investigating possible antiviral medications that may be administered to patients already exposed to the COVID-19 coronavirus. The institute’s goal is to quickly detect compounds in the clinic.
According to the research institute, a priority is to test drugs already approved or with significant safety data available in humans for activity against the virus, since these drugs are available for the treatment of patients with coronavirus. Can be done.
Scripps Research’s Division of Drug Development is using the Calibrate Collection, ReFRAME Drug Reurposing. The department has compiled ReFRAME.
A collection of known drugs that contain more than 14,000 compounds that have been approved for other diseases by the United States Food and Drug Administration (FDA) or extensively tested for human safety.
Caliber has also developed an open source database containing preclinical and clinical data on these compounds.
When the COVID-19 outbreak began, the department mobilized ReFRAME to begin the search for existing drugs and other compounds.
Previous studies have shown that some of these molecules appear effective against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Now, teams are testing all of the compounds against the new SARS-CoV-2 virus.
They are also investigating compounds that prevent the virus from initially infected cells. In a separate project, calibrate scientist Drs. Dennis is collaborating with Burton’s Scripps Research Laboratory to detect molecules that prevent SARS-CoV-2 from replicating after entering cells.
They hope that such a compound can serve as the basis for antiviral therapy. Another project being carried out by Calbride scientists is the detection of drugs that may increase the effectiveness of Gileadvir drug remedies that are currently being tested in five clinical trials of COVID-19.
The previous stages have partnered with pharmaceutical companies to detect antiviral drugs. COVID-19 treatment may already exist. This is how researchers can find these coronavirus medications.
Why do we not have medicines to treat COVID-19 and how long will it take to develop them?
SARS-CoV-2, the coronavirus that causes COVID-19 disease, is completely new and attacks cells in a novel way. Every virus is different, and therefore medications are used to treat them. That is why there was no medication ready to treat the new coronavirus that had been revealed a few months earlier.
As a systems biologist who describes how cells are affected by viruses during infection, I am particularly interested in the second question. It usually takes years to discover vulnerability points and develop medications to treat an illness.
But the new coronavirus is not giving the world that kind of time. With most of the world at risk of confinement and the risk of millions of deaths, researchers need to find an effective drug.
This situation has presented my colleagues and me with the challenge and opportunity of our lives: helping to resolve this enormous public and economic health crisis posed by the global SARS-CoV-2 pandemic.
In the face of this crisis, we assembled a team at the Institute for Quantitative Biosciences (QBI) at the University of California, San Francisco to discover how the virus attacks cells.
But instead of trying to make a new medicine based on this information, we first want to see if there is any medicine available today that can disrupt these pathways and fight coronaviruses.
The team of 22 laboratories, which we have called QCRG, works at breakneck speeds, literally 24 hours a day and in shifts, seven days a week. I imagine this was done during World War II in war efforts, like the Enigma code-breaking group, and our team hopes to destroy our enemy by understanding their inner workings.
A bitter opponent
Compared to human cells, viruses are small and cannot reproduce on their own. The coronavirus contains around 30 proteins, while a human cell contains more than 20,000.
To circumvent this limited set of devices, the virus skillfully pit the human body against itself. The pathways in a human cell are normally closed to external invaders, but coronaviruses use their own proteins like these to open “blockages” and enter a person’s cells.
Once inside, the virus binds to proteins, which the cell typically uses for its own function, essentially hijacking the cell and turning it into a coronavirus factory. As the resources and mechanics of infected cells are withdrawn to produce thousands upon thousands of viruses, the cells begin to die.
Lung cells are particularly vulnerable to this because they express high amounts of using the “blocked” protein SARS-CoV-2 for entry. The respiratory symptoms related to COVID-19 are caused by the large number of dying lung cells.
There are two ways to fight back. First, drugs can attack the virus’s own proteins, preventing them from entering the cell or acting as if they were mimicking its genetic material when inside it. This is how remdesivir, a drug currently in clinical trials for COVID-19, works.
One problem with this approach is that viruses change and change over time. In the future, coronavirus may develop so that a medicine like Remedisvir is useless. This is an arms race between drugs and viruses, so you need a new flu shot every year.
Alternatively, a drug can work by inhibiting viral proteins from interactions with a human protein that needs it. This approach, which essentially protects the machinery of the host, has a great advantage over the deactivation of the virus, since the human cell does not change rapidly.
Once you get a good medicine, it should continue to work. This is the approach our team is taking. And it can also work against other emerging viruses.
Learn the enemy plans
The first thing our group needed to do was identify each part of the cell factory that relies on the reproduction of the coronavirus. We need to find out what protein the virus hijacked.
To do this, a team from my laboratory conducted a molecular fishing expedition into human cells. Instead of hooking onto the hook, they used viral proteins with small chemical labels known as “bait.”
We put these forages into human cells grown in the lab and then took them out to see what we saw. All that was stuck was a human protein that the virus sequestered during infection.
As of March 2, we had a partial list of human proteins that coronaviruses need to thrive. These were the first tracks we were able to use. A team member texted our group, “First iteration, only 3 baits … The next 5 baits are coming.” The fight was on.
Once we have this list of molecular targets that the virus needs to survive, team members are quick to identify known compounds that can bind to these targets and use them to replicate the virus. You can stop doing it.
If a compound can prevent the virus from copying into a person’s body, the infection stops. But it cannot interfere with cellular processes without harming the body. Our team needed to make sure that the compounds we identified were safe and non-toxic to people.
The traditional way of doing it would involve years of preclinical studies and clinical trials costing millions of dollars. But there is a quick and basically free way.
And find 20,000 FDA approved drugs that have already been tested for safety. Perhaps there is a drug on this great list that can fight coronavirus.
Our chemists used a vast database to link approved drugs and proteins, which interact with the proteins on our list. He received 10 candidate drugs last week. For example, one of the successes was an anticancer drug called JQ1.
While we can’t predict how this drug can affect the virus, it has a good chance of doing something. Through testing, we find out if that helps some patients.
Faced with the threat of the closure of world borders, we immediately sent these 10 boxes of medicines to two of the few laboratories in the world that work with samples of live coronaviruses.
The Pasteur Institute in Paris and Mount Sinai in New York. By March 13, the drugs were being tested in the cells to see if they prevent the virus from reproducing.
Our team will soon learn from our colleagues in the bush. Sinai and the Pasteur Institute none of these top 10 medications work against SARS-CoV-2 infection. Meanwhile.
The team continued to fish with viral baits, finding hundreds of additional human proteins that are cooperatives of coronaviruses. We will soon post the results in the Biorexiv online repository.
The good news is that so far, our team has found 50 existing drugs that recognize human proteins. This large number makes me hope that we can find a medicine to treat COVID-19.
If we find an approved drug that slows the progression of the virus, doctors should be able to start it quickly and save lives for patients.
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This article was originally published in Conversation. The post contributed to a Live Science’s Expert Voices article: Op-Ed & Insights. This article is based on text provided by Southwestern Medical Center at the University of Texas.