Research rockstar Matthew Disney, PhD, and team from Scripps Florida have created drug-like compounds that based on results thus far in human cell studies, actually bind and destroy the “frameshifting element” associated with SARS-CoV-2, the virus behind COVID-19, hence inhibiting the virus from replication. The Scripps team in Jupiter, Florida, managed to engineer RNA-targeting compounds that disable this replication engine, a sort of “clutch-like device” that SARS-CoV-2 requires to produce replicates of itself once it enters cells. As Professor Disney emphasized in a recent Scripps press release, their compound stops the SARS-CoV-2 pathogen from actually shifting gears and thereby stops the disease in its tracks. The Scripps Research team in Jupiter means real business for this part of Florida—producing $3 billion worth of economic activity for the region in just the last 15 years.
Scripps explained in their recent press release that viruses such as COVID-19 enter the human cell and use that cell’s protein-production machinery to generate replicates of the virus. Of course, these are infectious and only serve to make the virus spread and the individual potentially very sick. The genetic material used to make it inside the cells must be incredibly compact and efficient, reports Scripps. It does this by “…[H]aving one string of genetic material encode multiple proteins needed to assemble new viruses. A clutch-like frameshifting element forces the cells’ protein-building engines, called ribosomes, to pause, slip to a different gear, or reading frame, and then restart protein assemble anew, thus producing different protein from the same sequence.”
Not Simple to Intervene
Scripps emphasizes the difficulty in intervening in this process. Because SARS-CoV-2 encodes its genetic sequence in RNA, and it’s been challenging to bind RNA with orally administered medicines expressed in Scripps in the press release.
The Scripps Breakthrough Built on 10+ Years of Research
However, the Scripps team, led by Disney, have been working to develop the tools to enable an intervention for over a decade. Titled “Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders,” the study surfaced online in the journal ACS Central Science.
A Big Step but a Ways to Go
However, there is a way to go, reports Disney, emphasizing a process of refinement of these tools must now occur. Hence, this new approach won’t support clinical trials tomorrow. However, the fact that the results are in demonstrate the feasibility of directly targeting viral RNA with small-molecule drugs opens heretofore not feasible possibilities. Disney believes RNA viral diseases can potentially be treated with this approach.
Emphasizing that this latest work represents a “proof-of-concept” study, Disney emphasized, “We put the frameshifting element into cells and showed that our compound binds the element and degrades it. The next step will be to do this with the whole COVID-19 virus, and optimize the compound.”
Disney and team collaborated with Walter Moss, PhD, Iowa State University Assistant Professor, in the process to analyze and predict the structure of molecules encoded by the viral genome, in search of its weaknesses.
Emphasizing the value of working together, Moss emphasized, “By coupling our predictive modeling approaches to the tools and technologies developed in the Disney lab, we can rapidly discover druggable elements in RNA.” Moss continued “We’re using these tools not only to accelerate progress toward treatments for COVID-19, but a host of other diseases as well.”
Disney and team’s work is, of course, supported by Scripps (their employer) and NH grants.
Scripps Research Florida
Scripps Research Florida is based in the scenic area of Jupiter, Florida. The campus encompasses three buildings on 30 lush acres within Palm Beach County’s innovation corridor. At this campus, dozens of principal investigators collaborate with laboratory members to understand disease and develop effective treatments. This group is regularly honored by the National Institutes of Health as well as numerous foundations for their discoveries. An elite team, they continue to pioneer innovations in translational research. The lead scientists are complimented by 500-member group of executives, staff scientists and graduate students as well as administrative assistants.
Last year, a study showcased the impact of Scripps Research in Florida: over the past decade and a half, Scripps Research, Florida, generated $3 billion in economic activity according to IMPLAN analysis, factoring in direct, indirect and induced impacts.
For list of other study authors see the source.