Sanford Burnham Prebys Medical Discovery Institute’s Sumit Chanda, PhD led a powerful team of scientists that have identified at least 21 existing drugs that stop the replication of SARS-CoV-2, the virus behind COVID-19. By analyzing the world’s largest collections of known drugs via Scripps Research ReFRAME library, the team reported 100 molecules with confirmed antiviral activity in the laboratory environment. The independent scientists further identified 21 actual drugs that at effective concentrations could be safety administered to patients. Four of these compounds could actually work synergistically with remdesivir, the current standard-of-care in the United States and some other nations. The top candidates include Clofazimine, Hanfangchin A, Apilimod and ONO 5334.
The Drug Library: ReFRAME Courtesy of Scripps Research
The research team leveraged the robust ReFRAME drug repurposing collection, what they claim is the most comprehensive drug repurposing collection of compounds that have been approved by the U.S. Food and Drug Administration (FDA) for other diseases or that have been tested extensively for human safety.
Apparently, ReFRAME was initially set up to help researchers study existing drugs to possibly apply to urgent global need in the areas of tropical disease for example reports study co-author Arnab Chatterjee, PhD, vice president of medicinal chemistry at Calibr. Chatterjee suggests that ReFRAME has become “an invaluable resource for screening for drugs to repurpose against the novel coronavirus.”
The ReFRAME library was developed by Calibr, the drug discovery division of Scripps Research under the leadership of President Peter Shultz, PhD, with funding from the Bill & Melinda Gates Foundation. The library is used by nonprofit collaborators to identify drug repurposing opportunities for a range of diseases such as TB and a parasite called Cryptosporidium and fibrosis.
The Power of Scientific Collaboration
Bringing this all together isn’t easy and often takes worldwide scientific collaboration. In this case the rapid screening was augmented by a partnership with Kwok-Yung Yuen, MD, chair of Infectious Diseases at the University of Hong Kong and Shuofeng Yuan, PhD, assistant professor in the Department of Microbiology at the University of Hong Kong. Both had access to the SARS-CoV-2 virus back in February.
The research team accessed massive drug collection in ReFRAME and performed extensive testing and validation studies including evaluation the drugs on human lung biopsies that were actually infected with the virus. The team also evaluated if the drugs could work synergistically with Remdesivir while establishing dose-responsive relationships between the drugs and antiviral activity.
Co-author Chanda suggests, “This study significantly expands the possible therapeutic options for COVID-19 patients, especially since many of the molecules already have clinical safety data in humans,” says Chanda. “This report provides the scientific community with a larger arsenal of potential weapons that may help bring the ongoing global pandemic to heel.”
21 Drugs Found to have Promise
Of the 21 drugs that were effective at blocking the viral replication, the team uncovered:
- 13 have previously entered clinical trials for other indications and are effective at concentrations, or doses, that could potentially be safely achieved in COVID-19 patients.
- Two are already FDA approved: astemizole (allergies), clofazamine (leprosy), and remdesivir has received Emergency Use Authorization from the agency (COVID-19).
- Four worked synergistically with remdesivir, including the chloroquine derivative hanfangchin A (tetrandrine), an antimalarial drug that has reached Phase 3 clinical trials
The Best Targets
Based on the analysis to date the team shared what they believe to be the best targets. Chanda reported that “Based on our current analysis, clofazimine, hanfangchin A, apilimod and ONO 5334 represent the best near-term options for an effective COVID-19 treatment.” Chanda continued, “While some of these drugs are currently in clinical trials for COVID-19, we believe it’s important to purse additional drug candidates so we have multiple therapeutic options if SARS-CoV-2 becomes drug resistant.”
The researchers continue to investigate these 21 compounds in small animal models and “mini lungs” known as lung “organoids” that mimic human tissue. IF the study results turn out positive the team plans on approaching the U.S. Food and Drug Administration (FDA) to discuss a clinical trial(s) to evaluate the drugs as treatments for COVID-19.
The Top Drugs
Clofazimine is sold under the brand name Lamprene and is a medication used together with rifampicin and dapsone to treat leprosy. It was discovered in the 1950s at Trinity College, Dublin and approved for medicinal use in the United States in 1986. Information about Hanfangchin A (L-Tetrandrine), a chloroquine derivative, is listed here while Apilimod is drug that was initially identified as an inhibitor of production of the interleukins IL-12 and IL-23 and developed for the oral treatment of autoimmune conditions such as Crohn’s disease and rheumatoid arthritis though there were disappointing clinical trials. Finally ONO 5334 appears to be a discontinued compound from Japanese drug maker Ono Pharmaceuticals.
What is Sanford Burnham Prebys?
Sanford Burnham Prebys is a La Jolla, CA-based preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. The group has been in operation for over 40 years and has produced research breakthroughs in cancer, neuroscience, immunology and children’s diseases and is anchored in their NCI-designated Cancer Center and advanced drug discovery capabilities.
The Sanford Burnham Prebys Medical Discovery Institute is a 501(c)(3) non-profit medical research institute focusing on basic and translational research with major research programs, such as cancer, neurodegeneration, diabetes and infectious, inflammatory and childhood diseases. The institute employs over 700 scientists and staff at its La Jolla, California, campus.
Note a large team was involved in this endeavor and can be viewed at the source.
Call to Action: TrialSIte Network: This is big news. Focus research to vet and verify the Sanford Burnham Prebys findings including the top candidates against COVID-19 of clofazimine, hanfangchin A, apilimod and ONO 5334.