Why don’t we have more COVID-19 drugs?

Even when the vaccines are out, the holy grail of the epidemic – Covid-19 – continues to successfully cure the disease.

On Monday, a World Health Organization panel asked scientists to stop researching poster child for drugs that failed to work against hydroxychloroquine, a carotenoid virus. Meanwhile, more than 40,000 people across the country are still hospitalized with COVID-19, and only a few simple treatments can help treat them. And with new types of vaccines threatening to fail, finding drugs to fight SARS-Co-2 is even more urgent.

“What we need to look forward to, and the obvious need for this is the development of powerful antivirals that work directly on SARS-CAV-2,” Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, said in a White House briefing last week . Antivirals will revolutionize the fight against SARS-CoV-2, as they prevent the virus from copying and can prevent people from getting too sick or dying.

But efforts to develop such drugs have failed due to a lack of funding and coordination: while the pace of operation and speeds has almost failed to develop vaccines. While allocating. 18.75 billion, it set aside only 3 6.34 billion for drugs. Instead, scientists tried to reintroduce older diseases, including antivirals for other diseases, to see if they worked against COVID-19.

“Everyone was looking for a quick fix,” Fawcett told BuzzFeed News. The FDA has so far authorized only one drug for the treatment of Comido-19, a remedial, initially developed against Ebola. But it’s far from a complete drug: the results of how it affects the length of hospital stay have been mixed, and it has not been shown to reduce mortality.

“There’s nothing wrong with finding quick fixes, but you also have to work for a long-term investment,” Fauci said, adding that the search for effective new drugs would take anywhere from months to a year. He said the goal would be to develop clearly designed and targeted drugs, such as SARS-CoV-2, a “spectacular success” against HIV and hepatitis C, that would make it suitable for the treatment of life-threatening diseases. Said.

But that hasn’t happened yet. After evaluating hundreds of older drugs, national health organizations have no new antivirals for COVID-19 in public-private partnerships of clinical trials called Accelerating COVID-19 Therapeutic Interventions and Vaccinations (ACTIV). There are no newly designed antivirals listed in the 160 NIH-supported clinical trials reported by the National Library of Medicine. The “Medical Countermeasures” effort to speed up Operation Operation also does not include any new antivirals.

The only new treatment on the active list is monoclonal antibodies – such as those taken by former President Donald Trump – that are difficult to give to patients because they require a long period of hours near the onset of the disease.

Scientists have tried to recreate older drugs to help treat COVID-19 – without much success.

The most successful reprogrammed drug in the epidemic is dexamethasone, a steroid discovered in 1957 – not so long ago, Fawcett said he prescribed it in graduate school. Instead of attacking the coronavirus, dexamethasone will suppress the immune system, which can turn the body against itself and attack vital organs in the later stages of Covid-19. This inexpensive and safe drug has reduced mortality in COVID-19 patients on a ventilator by almost a third, an inescapable argument for finding a second needle in the grass of older drugs that could work directly against the virus.

“There are many reasons to use FDA-approved drugs because they already have known properties in human patients,” said Texas A&M biochemist Wenshe Ray Liu, who is researching both new and regenerative drugs to fight coronavirus. . And testing it is relatively easy: companies only have to dose infected cells in a test tube with their existing drug library and find out that SARS-CoV-2 is blocked. Because they have already been examined, the winner can go straight to clinical trials without having to do extensive studies to show they are safe.

Clinical trials are expensive, Liu added, and pharmaceutical companies prefer to test drugs that have already cost money to develop. For both of those reasons, drug companies have largely advanced small clinical trials with large numbers of patients showing that their own drugs work, hitting the home run. It gives little incentive for patients to sign up to be tested for experimental drugs in the early stages of the disease when they are not very ill.

An antiviral, Molnupiravir, designed to fight the flu, is an example of the challenges facing clinical trials to test promising drugs. Safety trials seemed promising for the drug this summer, and drug company Merck began a large clinical trial of 1,300 patients in October to see if it would lower virus levels. It is expected to end in December 2021, taking three to four times as long as vaccine testing in which thousands of people were registered. On top of other challenges, the study move reduced viral loads rather than improving patients ’symptoms, which may not convince the FDA of its benefits.

One of the reasons for this type of obstruction is that re-established medications do not show much benefit in patients. And while scientists funded by the NIH are studying more than a dozen older drugs for diseases such as arthritis, cancer, malaria, hepatitis or arthritis to see if they can fight SARS-CV-2, in clinical trials It is the only antiviral in addition to rimadesivir. Japanese pancreatic medicine developed in the 1980s. The results of the trial, which began last August, are projected for the end of this year.

The results of small tests for melanpiravir may be similar to those of Manny, said Victor Garcia-Martinez, a virologist at the University of North Carolina, who led a February study that showed the drug was more effective in mice equipped with lung tissue. If it ultimately proves effective, Garcia-Martinez said, “It will be easier to produce and distribute. Especially if an epidemic has spread, say, in a nursing home, you can spread it to people right away. “

There are characteristics of coronavirus that make it difficult to find an effective drug to fight it – but there is reason to be optimistic.

Martin Michaelis, a drug researcher at the University of Kent in the United Kingdom, said many drugs routinely block the virus in test tubes, as do other coronaviruses. Scientists were initially optimistic that the drugs would work similarly against SARS-Covy-2, but the virus is so different that most of these drugs may not be effective.

In a recent study, Michaelis and colleagues reported differences between SARS-COV-2 and its immediate human-infected, SARS virus, which killed 774 people since the 2002 outbreak. Michaelis and his colleagues found that they were genetically about 0% identical, and that the two viruses differed in the biological machinery used to replicate within cells. This is important because interfering with this viral replication is the main function of antiviral drugs. If viruses cannot replicate, they cannot spread.

Now that the spikes outside of the coronavirus are mutating wildly to produce more infectious forms, the virus has less freedom to alter its reproductive process, Michaelis said. That’s why the same machinery is important in other basic viral functions as well, making it a more reliable target for drugs targeting the virus.

“You can’t say that these protected areas will never change,” he said, “but that’s unlikely.” “

Examples of new antivirals designed against SARS-Covy-2 are now advancing in animal studies. A February 18 report by Chinese researchers in the journal Science found that two drugs successfully reduced the viral load in rat lungs.

And there are other signs that we may find helpful COVID-19 drugs. One year after the epidemic, scientists know more about how SARS-CoV-2 works and may be better equipped to find existing drugs that can attack it, said Liu of Texas A&M Was. His team recently found a high blood pressure medication that sits like a key to a coronavirus lock in a computer simulation. The drug can be ignored because it is common and does not have a clinical sponsor willing to invest in a clinical trial.

“If we can’t find a corporate sponsor, we will try to start our own clinical trial.”

The more we treat the vaccine, the more money is needed for the hard pressure.

When the epidemic was first declared by the WHO on March 11, 2020, Fawcett testified before Congress that there were two ways to address the coronavirus: vaccines or drugs.

From a scientific point of view, there were many reasons to expect an antiviral drug to be started sooner than a single vaccine, Fawcett told BuzzFeed News. “You usually know relatively quickly [drug] Whether the treatment works or not because you are already treating someone who is sick, ”he said.

One vaccine, meanwhile, has to give thousands of people real shots and placebos and then wait until the natural infection is effective enough to cause an infection.

“We were lucky that we had a couple of vaccine candidates who were red-hot and turned out to be really good,” Fawcett said. “And unfortunately for the country, but fortunately for vaccine tests, we continued to get high levels of infection, which allowed us to get the answer quickly.”

Michaelis added that vaccines stimulate a better-understood natural immune response than newer anticoagulants, making their design and safety testing more straightforward. But U.S. vaccine testing also had more funding than treatment.

“Antiviral drugs for acute diseases do not have enough money to be used for only a week or more,” Michaelis said. The lack of a clear path is that new antivirals clearly designed against coronaviruses will require large public investment, Fath said. Francis Collins, head of the NIH, told the New York Times that the NIH recently launched an initiative to research new antivirals, which “may not be curable in 2021”.

In some ways, the lack of COVID-19 antivirals indicates how lucky humanity is to have effective vaccines, Michaelis said.

“People have tried a lot of combinations against SARS-Covi-2, Covid-19, but they don’t have a big, big, successful candidate yet.” Continuing to create new drugs, he added, “harder and harder.”