SARS-CoV-2, the virus responsible for COVID-19, has actually damaged health care systems, economies, and everyday lives worldwide. Researchers are resisting with numerous strategies, including vaccines, repurposed drugs established for other diseases and brand-new therapies. Now, researchers reporting in A/C Central Science have actually determined small molecules that target a structure within the RNA genome of SARS-CoV-2, disrupting viral gene expression and targeting the RNA for destruction.
The SARS-CoV-2 RNA genome folds into distinct shapes that can possibly be targeted by drugs. One area of the RNA, called the frameshifting element (FSE), includes a hairpin and other structures that help the virus equate its genes into proteins.
The researchers started by carrying out microarray experiments to determine little particles that bind to a particular region of the SARS-CoV-2 FSE barrette. One particle, which they called substance 5 (C5), reduced the barrette’s effectiveness in assisting the infection equate its genes by about 25%in cell culture experiments, minimizing the capability of SARS-CoV-2 to make vital proteins. To enhance the effectiveness of C5, the group attached a molecule (called a ribonuclease-targeting chimera, or RIBOTAC) that recruits a human enzyme that breaks down the viral RNA. In cultured cells, RIBOTAC increased the strength of C5 by about 10- fold.
Although far more work is needed to establish the RIBOTAC-containing compound into a drug, these findings suggest that the SARS-CoV-2 genome can be targeted by small particles that disrupt its function, the researchers state.
For more on this discovery, read Breaking COVID-19’s “Clutch” to Stop Its Spread
Referral: “Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders” by Hafeez S. Haniff, Yuquan Tong, Xiaohui Liu, Jonathan L. Chen, Blessy M. Suresh, Ryan J. Andrews, Jake M. Peterson, Collin A. O’Leary, Raphael I. Benhamou, Walter N. Moss, and Matthew D. Disney, 30 September 2020, ACS Central Science
DOI: 10.1021/ acscentsci.0 c00984
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