(Press-News.org) June 3, 2021 - LA JOLLA, CA--Mining the world's most comprehensive drug repurposing collection for COVID-19 therapies, scientists have identified 90 existing drugs or drug candidates with antiviral activity against the coronavirus that's driving the ongoing global pandemic.
Among those compounds, the Scripps Research study identified four clinically approved drugs and nine compounds in other stages of development with strong potential to be repurposed as oral drugs for COVID-19, according to results published June 3 in the journal Nature Communications.
Of the drugs that prevented the coronavirus from replicating in human cells, 19 were found to work in concert with or boost the activity of remdesivir, an antiviral therapy approved for treatment of COVID-19.
"While we now have effective vaccines against COVID-19, we still lack highly effective antiviral drugs that can prevent COVID-19 infections or stop them from worsening," says Peter Schultz, PhD, president and CEO of Scripps Research.
"Our results raise the possibility of a number of promising avenues for repurposing existing oral medications with efficacy against SARS-CoV-2," he adds. "We have identified promising existing drugs and are also leveraging our findings to develop optimized antivirals that will be more effective against SARS-CoV-2, including variants and drug resistant strains, as well as against other coronaviruses that currently exist or might emerge in future."
In a collaboration between Calibr, the drug discovery division of Scripps Research, and a team of researchers in the institute's Department of Immunology and Microbiology, the study tested more than 12,000 drugs in two different types of human cells infected with SARS-CoV-2.
The drugs used in the study came from the ReFRAME drug repurposing library, which was established by Calibr in 2018 with support from the Bill & Melinda Gates Foundation to tackle areas of urgent unmet medical need, especially neglected tropical diseases. The collection contains FDA-approved drugs and other experimental compounds that have been tested for safety in humans.
"Early in the COVID-19 pandemic, we saw that ReFRAME could be leveraged to screen for hits against SARS-CoV-2," says Arnab Chatterjee, PhD, vice president of medicinal chemistry at Calibr. "In the months that followed, we launched many scientific collaborations to speed drug discovery, both internally at Scripps Research and with partners nationally and internationally."
In the Scripps Research study, the scientists treated two different types of laboratory-cultured SARS-CoV-2-infected human cells with each of the 12,000 drugs from ReFRAME. After 24 or 48 hours, they measured the level of viral infection in the cells to determine if the drugs prevented the virus from replicating. In some cases, they applied two drugs at a time to see if the compounds would work together against the virus.
"Some of the most effective antiviral strategies are 'cocktails' in which patients are given several different drugs to combat the infection, such as those used to treat HIV infections," says the study's corresponding author Thomas Rogers, MD, PhD, an adjunct assistant professor in the Department of Immunology and Microbiology at Scripps Research and assistant professor of Medicine at UC San Diego.
From the thousands of drugs screened, the researchers identified a total of 90 compounds that prevented SARS-CoV-2 from replicating in at least one of the human cell lines. Of those, 13 had the highest potential to be repurposed as COVID-19 therapies, based on their potency, cell line-independent activity or a likely mechanism of action, pharmacokinetic properties and human safety profiles.
Four of the drugs--halofantrine, nelfinavir, simeprevir and manidipine--are already FDA approved and nine others are in various stages of the drug development process.
From the drug combination screens, the researchers found 19 drugs that had an additive effect when administered with remdesivir, the antiviral produced by the pharmaceutical company Gilead that is FDA approved for use in patients diagnosed with COVID-19. An additive effect means that the drugs were both active against the virus when applied together.
"The potential advantage of a therapeutic strategy that uses a combination of drugs is that taking a lower dose of any one drug could reduce the risk of side effects of that drug," says Malina Bakowski, PhD, the lead author on the Nature Communications paper and principal investigator at Calibr.
Two additional drugs went a step further to have a synergistic effect on remdesivir, meaning the drugs heightened remdesivir's ability to suppress the virus. These two drugs were riboprine, a compound that's been tested as a preventative for nausea and surgical infection, and 10-deazaaminopterin, a derivative of the vitamin folic acid.
Based on the results of cell culture screens, the researchers tested the best-performing drug candidates in human tissue cells and an animal model to determine which are most likely to work in human patients. Building on their success in identifying potential COVID-19 therapies, the Scripps Research team is continuing to advance other promising candidates through their drug discovery pipeline.
"The results from the cellular assays and animal models are very promising and the need for medical remedies to address COVID-19 remains urgent," says Schultz. "It is critical we proceed with the utmost rigor to determine what is safe and effective, as diligence is the most expedient path to finding new therapies that will make a difference for patients."
Results from the screen of the ReFRAME library are available at the reframedb.org data portal.
INFORMATION:
"Drug repurposing screens identify chemical entities for the development of COVID-19 interventions" was coauthored by Malina Bakowski, Nathan Beutler, Karen Wolff, Melanie Kirkpatrick, Emily Chen, Tu-Trinh H. Nguyen, Laura Riva, Namir Shaabani, Mara Parren, James Ricketts, Anil Gupta, Kastin Pan, Peiting Kuo, MacKenzie?Fuller, Elijah Garcia, John Teijaro, Linlin Yang, Debashis Sahoo, Victor Chi, Edward Huang, Natalia Vargas, Amanda Roberts, Soumita Das, Pradipta Ghosh, Ashley Woods, ?Sean Joseph, Mitchell Hull, Peter Schultz, Dennis Burton, Arnab Chatterjee, Case McNamara and Thomas Rogers. Funding for the study was provided by the Bill & Melinda Gates Foundation, the National Institutes of Health and the Sanford Stem Cell Clinical Center at UC San Diego Health.
MIT researchers have created the first fiber with digital capabilities, able to sense, store, analyze, and infer activity after being sewn into a shirt.
Yoel Fink, who is a professor of material sciences and electrical engineering, a Research Laboratory of Electronics principal investigator, and the senior author on the study, says digital fibers expand the possibilities for fabrics to uncover the context of hidden patterns in the human body that could be used for physical performance monitoring, medical inference, and early disease detection.
Or, you might someday store your wedding music in the gown you wore on the big day -- more on that later.
Fink and his colleagues describe the features of the digital fiber in Nature Communications. Until now, electronic fibers ...
The number of people engaging with life-enhancing cardiac rehabilitation clinics has declined during the pandemic, according to a BMJ clinical update which makes the case for more home-based and virtual alternatives.
Before the covid-19 pandemic, 100?000 people were admitted to hospital with heart attacks and approximately 200?000 were diagnosed with heart failure annually in the UK. There was a 40% decline in the number of patients admitted with heart attacks (acute coronary syndromes ) in 2020.
Cardiac rehabilitation is crucial to helping people who have encountered a heart attack or heart failure have a better quality of life. Now, a new review, undertaken by cardiac rehabilitation experts based at the ...
WASHINGTON, DC - JUNE 3, 2021 -- A new West Health/Gallup survey finds nearly all Democrats (97%) and the majority of Republicans (61%) support empowering the federal government to negotiate lower prices of brand-name prescription drugs covered by Medicare. Overall, 8 in 10 Americans prefer major government action to control prices over concerns about it hurting innovation and competition from the pharmaceutical industry. The results come from a nationally representative poll of more than 3,700 American adults.
While President Joe Biden, Democrats in Congress and former President Donald Trump have called for such negotiation, ...
If you have ever tried to chip a mussel off a seawall or a barnacle off the bottom of a boat, you will understand that we could learn a great deal from nature about how to make powerful adhesives. Engineers at Tufts University have taken note, and today report a new type of glue inspired by those stubbornly adherent crustaceans in the journal Advanced Science.
Starting with the fibrous silk protein harvested from silkworms, they were able to replicate key features of barnacle and mussel glue, including protein filaments, chemical crosslinking and iron bonding. The result is a powerful non-toxic glue that sets and works as well underwater as it does in dry conditions and is stronger than most synthetic glue products now on the ...
People who use methamphetamine are more likely to have health conditions, mental illness, and substance use disorders than people who do not use the drug, according to a new study by researchers at the Center for Drug Use and HIV/HCV Research (CDUHR) at NYU School of Global Public Health. The findings are published in the Journal of General Internal Medicine.
The use of methamphetamine--a highly addictive and illegal stimulant drug--has increased in recent years, as have overdose deaths. Methamphetamine can be toxic for multiple organs including the heart, lungs, liver, and neurological system, and injecting the drug can increase one's risk for infectious diseases.
"Methamphetamine can complicate the management of existing chronic ...
A new study in the journal Sleep finds that increased evening screen time during the Covid-19 lockdown negatively affects sleep quality.
During the lockdown period in Italy, daily internet traffic volume almost doubled compared to the same time in the previous year. Researchers here conducted a web-based survey of 2,123 Italian residents during the third and seventh week of Italy's first national lockdown. The survey ran in the third week of lockdown (March 25th - 28th, 2020) and evaluated sleep quality and insomnia symptoms, using the Pittsburgh Sleep ...
A study published in the journal Pediatrics shows the combination of two early reading programs had positive effects on preschool students entering kindergarten in Cincinnati Public Schools over a three-year period.
The two early reading programs are: Reach Out and Read, through which children receive a new book and guidance about reading at home during well-visits from newborn through age 5; and Dolly Parton's Imagination Library, which mails new books to the child's home once a month from birth through age 5. Each of these is well-established at Cincinnati Children's Hospital Medical Center and across the nation.
"With this early study, we suggest that when combined and sustained, ...
CHAMPAIGN, Ill. -- Many species of ground-dwelling beetles, ladybugs, hoverflies, damsel bugs, spiders and parasitic wasps kill and eat pest species that routinely plague farmers, including aphids and corn rootworm larvae and adults. But the beneficial arthropods that live in or near cropped lands also are susceptible to insecticides and other farming practices that erase biodiversity on the landscape.
A new study reveals that beneficial arthropods are nearly twice as abundant and diverse in uncultivated field edges in the spring as they are in areas that ...
A University of Birmingham-led study of over a thousand dental professionals has shown their increased occupational risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK.
The observational cohort study, published today (3 June 2021), in the Journal of Dental Research, involved 1,507 Midland dental care practitioners. Blood samples were taken from the cohort at the start of the study in June 2020 to measure their levels of antibodies against SARS-CoV-2, the virus that causes COVID-19.
The team found 16.3% of study participants - which included dentists, dental nurses and dental hygienists - had SARS-CoV-2 antibodies, compared to just 6% of the general population at the time. Meanwhile, the percentage of dental ...
Scientific papers suggesting that smokers are less likely to fall ill with covid-19 are being discredited as links to the tobacco industry, reveals an investigation by The BMJ today.
Journalists Stéphane Horel and Ties Keyzer report on undisclosed financial links between certain scientific authors and the tobacco and e-cigarette industry in a number of covid research papers.
In April 2020, two French studies (shared as preprints before formal peer review) suggested that nicotine might have a protective effect against covid-19 - dubbed the "nicotine hypothesis."
The stories made headlines worldwide ...
