Coronavirus: 30 drugs promise to fight the disease



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The team came up with promising compounds after
The team came up with promising compounds after analyzing a library of more than 12,000 substances – a bank created to help fight deadly diseases (photo: Rob Engellar / AFP – 3/4/20)

Thirty medicines and safe for human use hold promise to combat Covid-19, found a team of North American and Hong Kong researchers. The scientists launched a study on the bioRxiv open platform in which they describe three dozen substances that prevent the replication of Sars-Cov-2, of which only three of them are already being tested for this purpose. According to them, until now, no other group had identified the other remedies as promising, increasing the number of candidates to face the coronavirus, without having a vaccine.

The drugs were identified by detecting more than 12,000 substances from the ReFRAME Drug Redirection Collection, a library of molecules that has been approved by the United States Food and Drug Administration (FDA) for other diseases or that have been Thoroughly tested to ensure your safety. for use in humans.

ReFRAME was created by the Scripps Research institute in California to accelerate efforts to combat deadly diseases. All compounds were tested against live Sars-Cov-2, isolated from patients in Washington state and China. Of these, 30 drugs were selected based on their ability to stop viral replication.

“We believe this is one of the first comprehensive investigations for drugs using the live Sars-Cov-2 virus, and we hope that one or more of these drugs will save lives while we wait for a vaccine for Covid-19,” says Sumit Chanda, director. from the Sanford Burnham Prebys Immunity and Pathogenesis Program at the University of California, Los Angeles, and lead author of the study. “Many drugs identified in this study, many of which are new to the Covid-19 research community, can be used in clinical trials immediately or within a few months after further testing.”

“For us, the starting point for finding any new antiviral medication is to measure its ability to block viral replication in the laboratory,” says Chanda. “Since the drugs we identified in this study have already been tested in humans and shown to be safe, we can skip over half a decade of studies that are normally needed to obtain approval for human use.”

Chanda’s team partnered with the scientist who discovered the first SARS virus, Kwok-Yung Yuen, director of infectious diseases at the University of Hong Kong; and with Shuofeng Yuan, assistant research professor in the Department of Microbiology at the same institution, who had access to Sars-Cov-2 alive in February. Together, the labs recreated Chanda’s high-tech automated technology and reviewed the drugs in Yuen’s lab. There, they identified 300 drugs from the ReFRAME library that could keep cells alive, despite Sars-Cov-2 infection.

Tolerable doses
These 300 drugs advanced to a second round of testing at Chanda’s laboratory in La Jolla, California. There, the researchers used molecular tools, such as polymerase chain reaction (PCR) and immunofluorescence microscopy, to identify 30 compounds that were most effective in stopping viral replication.

Of the 30, 27 medications currently not being evaluated for Covid-19 were effective in stopping viral replication. Of these, 17 have an extensive human safety history in clinical studies in non-Covid-19 related diseases, including four that were previously approved by the FDA for other indications.

So far, six of the 17 have been shown to be effective in concentrations, or doses, that are likely to be effective and tolerable in humans. Four of these have been clinically tested to detect diseases such as rheumatoid arthritis, Crohn’s disease, osteoporosis, and cancer.

In addition to the 27 candidate drugs, three currently in clinical trials for Covid-19, including remdesivir and chloroquine derivatives, have been shown to be effective in stopping the replication of Sars-Cov-2. According to Chanda, “the results reaffirm their promise as possible treatments for Covid-19 and support the continuation of ongoing clinical trials to demonstrate their effectiveness in patients.”

Clinical trials
Depending on regulatory guidance, newly identified drug candidates may proceed directly to Covid-19 clinical trials or undergo additional tests of effectiveness in animal models. “Based on the extensive data in this study, we believe that four described medications represent the most promising new approaches to short-term treatment of Covid-19,” says Chanda. “However, we believe that all 30 candidates should be fully explored, as they were clearly active and effective in our testing.”

Chanda’s team was able to work with the live virus because his laboratory is certified as Biosafety Level 3, or BSL-3, which means that he is equipped with safeguards to protect laboratory personnel, as well as the environment and the surrounding community. . pathogens that can cause serious or life-threatening illness. The facility was created in 2016 to support research on broad-spectrum antivirals, drugs that work against many viruses, for HIV, the flu, dengue, and West Nile virus.

“We have chosen to disclose these findings to the scientific and medical community now to help resolve the current global health emergency,” says Chanda. “The data from this drug test is a treasure, and we will continue to extract information from this analysis to find additional candidates, alone or in combination, as they are identified.”

“A priority for our team to test approved drugs, or drugs with significant available human safety data, for activity against Sars-Cov-2,” says researcher Dennis Burton, head of the laboratory at Scripps where the compounds are being identified . “These drugs may be available to treat coronavirus patients on a much faster time scale than new therapies,” he says.

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