Why don’t you have more COVID-19 medications?

Even with the launch of the vaccine, the Pandemic Holy Grail, a drug that successfully treats COVID-19, continues to miss the drug.

World Health Organization panel to scientists on Monday Stop research Hydroxychloroquine, poster child of drugs that failed to counteract Coronavirus.. in the meantime, Over 40,000 He is still hospitalized nationwide with COVID-19 and only a handful of mediocre treatments can help treat them. And with new variants that can block vaccines, finding drugs to fight SARS-CoV-2 is becoming more and more urgent.

“The point we are looking forward to, and the clear need for this, is the development of a potent antiviral drug that acts directly on SARS-CoV-2,” said the director of the National Institute of Allergy and Infectious Diseases. Anthony Forch says. I said at a White House briefing last week. Antivirals will revolutionize the fight against SARS-CoV-2 because they can block the replication of the virus and prevent people from becoming very ill or dying.

However, efforts to develop such drugs have declined due to lack of funding and coordination: while Operation Warp Speed ​​is devoted. Almost $ 18.75 billion To develop the vaccine, it set aside only $ 6.34 billion for the drug. Instead, scientists sought to reuse old drugs, including antiviral drugs for other illnesses, to see if they could counter COVID-19.

“Everyone was looking for a quick solution,” Fauci told BuzzFeed News. To date, the FDA has approved only one drug to treat remdesivir, the first COVID-19 developed for Ebola.But it’s far from the perfect drug: results on how it affects hospital stay Mixed, And it has not been shown to reduce death.

“Finding a quick solution is fine, but it also requires a long-term investment,” Forch said, finding an effective new drug can take months or a year. The goal is to explicitly design and target SARS-CoV-2, like the “superbly successful” drugs made for HIV and hepatitis C that have made it possible to treat fatal illnesses. He said it was to develop a drug.

But that hasn’t happened yet.After evaluating hundreds of old drugs, the National Institutes of Health does not have a new antiviral drug for COVID-19 in it Public-private partnership Accelerated COVID-19 of a clinical trial called intervention and vaccine (ACTIV).There is No newly designed antivirals Listed in Clinical trials supported by 160NIH It is registered by the National Library of Medicine. Operation Warp Speed ​​”Medical measuresThe efforts do not include new antivirals.

The only new treatment on the ACTIV list is monoclonal antibodies. Taken by former President Donald Trump -is this Difficult to give to patients Because they need an hour of blood transfusion near the onset of the disease.

Scientists have tried to reuse old drugs to help treat COVID-19, but with little success.

The most successful reused drug in the pandemic was dexamethasone, a steroid invented in 1957 — long ago Forch said he prescribed it in graduate school. Instead of attacking the coronavirus, dexamethasone suppresses the immune system. The immune system can turn its body toward itself and attack important organs in the later stages of COVID-19.This cheap and safe drug reduced the mortality rate of COVID-19 patients using ventilators About one-thirdA compelling argument to look for another needle in a pile of old drug hay that may act directly on the virus.

“There are many reasons to use these FDA-approved drugs because they already know the characteristics of human patients,” said Wenshe Ray Liu, a Texas A & M biochemist who studies both. New and reusable drugs To fight the coronavirus. And those tests are relatively easy. Companies simply administer a library of existing drugs to infected cells in vitro to elicit what appears to be blocking SARS-CoV-2. Since they have already been scrutinized, winners can enter clinical trials directly without extensive research to show that they are safe.

Clinical trials are expensive, Liu adds, and pharmaceutical companies prefer to test drugs that they have already spent money on developing.For both of these reasons, pharmaceutical companies have primarily pursued small-scale clinical trials. Too few patients Hoping to hit a home run, to show that their own medicine worked. Those patients have little incentive to sign up to test drugs in the early stages of their illness when they are not severely ill.

Molnupiravir, an antiviral drug designed to combat influenza, is an example of the challenges faced by clinical trials to test promising drugs.This summer’s safety trials seem promising for the drug, started by pharmaceutical company Merck Larger clinical trials Of 1,300 patients in October to see if it lowers virus levels. Scheduled to end in December 2021, it will take three to four times longer than a vaccine trial involving tens of thousands of people. In addition to other challenges, this study measures reducing viral load rather than improving a patient’s symptoms. May not convince the FDA Of its advantages.

This type of hurdle is one of the reasons why reused drugs have shown little benefit to patients. Also, whether NIH-funded scientists can fight SARS-CoV-2 by studying more than 12 older drugs for diseases such as arthritis, cancer, malaria, hepatitis, and gout. However, in clinical trials, the only antiviral drug other than remdesivir is a Japanese hepatitis drug developed in the 1980s. The results of the trial, which started in August last year, are predicted at the end of this year.

Results of small tests Victor Garcia Martinez, a virologist at the University of North Carolina, said Molnupiravir should come sooner. February study This drug has been shown to be very effective in mice with human lung tissue.Announced by Ridgeback Biotherapeutics, which is being developed in collaboration with Merck Some preliminary results From that exam in 202 inpatient adults at a science conference on Saturday morning. They showed a faster reduction in viral levels in nasal swabs in patients who took the drug compared to those who did not. The company hopes to present full results at future medical conferences to show whether the drug has eliminated the virus faster and more completely.

When finally proven to work, Garcia Martinez said: Especially if it happens in a nursing home, for example, it can be delivered to people immediately. “

Coronaviruses are characterized by the difficulty of finding effective drugs to combat them, but there are reasons for hope.

According to Martin Michaelis, a drug researcher at the University of Kent in the United Kingdom, many drugs regularly block in vitro viruses and even other coronaviruses. Scientists were initially optimistic that these drugs would act similarly on SARS-CoV-2, but the virus is so different that most of these drugs are effective. May not be.

To Recent research, Michaelis et al. Explained the difference between SARS-CoV-2 and its closest relative, the SARS virus, which infects humans. Killed 774 people After the outbreak in 2002. Although they are genetically similar by about 80%, the two viruses differ in the biological mechanisms they use to replicate intracellularly, Michaelis and his colleagues found. This is important because blocking this viral replication is the main task of antiviral drugs. If the virus cannot replicate, it cannot spread.

Although the outer spikes of the coronavirus are now violently mutated and produced More contagious variantsThe virus has less freedom to change its reproductive process, Michaelis said. This is because the same mechanism is essential for other basic viral functions and is a more reliable target for virus-targeting drugs.

“We can’t say that these conserved regions never mutate, but it’s a lower probability,” he said.

Examples of new antiviral drugs specifically designed for SARS-CoV-2 are now being revealed in animal studies.A February 18 report by a Chinese researcher in a scientific journal found that: Two medicines We have succeeded in reducing the viral load in the lungs of mice.

And there are other signs that we may find useful COVID-19 drugs. A year after the pandemic, scientists know more about how SARS-CoV-2 works and to find existing drugs that could attack SARS-CoV-2. May be ready, said Liu of Texas A & M. His team recently discovered a hypertensive drug that fits like the key to a coronavirus in computer simulations. This drug is a generic drug and may be overlooked because no corporate sponsor is willing to invest in clinical trials.

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

It takes more money to push the treatment as strongly as we did with the vaccine.

March 11, 2020, the day the pandemic was first declared by WHO, Fauci Testimony to Congress There were two ways to deal with the coronavirus: vaccines and drugs.

From a scientific point of view, there were many reasons to expect effective antivirals to appear sooner than vaccines, Fauci told BuzzFeed News. “You are generally [drug] I’m treating people who are already ill, so I’m not sure if the treatment will work, “he said.

Vaccines, on the other hand, need to give tens of thousands of people real injections and placebo and wait until a natural infection causes enough infection to show that it is effective.

“Fortunately, there were some vaccine candidates that turned out to be very hot and really good,” Fauci said. “And unfortunately for the country, but fortunately for the vaccine trial, we continued to have high levels of infection, so we were able to get an answer fairly quickly.”

Vaccines provoke a well-understood natural immune response, making their design and safety testing easier compared to new antiviral drugs, Michaelis added. However, US vaccine trials also had significantly more funding than those for treatment.

“There isn’t much money for antiviral drugs for acute illnesses that are only used for a week or so,” Michaelis said. The lack of a clear path means that new antivirals specifically designed for the coronavirus are likely to require significant public investment, Forch said. NIH recently launched an initiative to research new antiviral drugs.It is unlikely to offer a therapeutic drug in 2021NIH Chief Francis Collins told The New York Times.

In some respects, the lack of COVID-19 antivirals underscores how lucky humans are to have an effective vaccine, Michaelis said.

“People have tried so many compounds against SARS-CoV-2, COVID-19, but so far no big and successful candidates have been found,” he said. He made progress towards the development of new drugs, adding that “it will be more and more difficult.”