Newswise — SARS-CoV-2, the virus responsible for COVID-19, has wreaked havoc on health care systems, economies and everyday lives worldwide. Scientists are fighting back with multiple strategies, including vaccines, repurposed drugs developed for other diseases and brand-new therapies. Now, researchers reporting in ACS Central Science have identified small molecules that target a structure within the RNA genome of SARS-CoV-2, interfering with viral gene expression and targeting the RNA for destruction.
The SARS-CoV-2 RNA genome folds into unique shapes that can potentially be targeted by drugs. One region of the RNA, called the frameshifting element (FSE), contains a hairpin and other structures that help the virus translate its genes into proteins. Matthew Disney, Hafeez Haniff, Yuquan Tong and colleagues wondered if they could identify a small-molecule drug that could bind to the hairpin and prevent it from doing its job. They also wanted to see if they could increase the drug’s potency by adding a component that would attract an RNA-chopping cellular enzyme to destroy the virus’ genome.
The researchers began by conducting microarray experiments to identify small molecules that bind to a specific region of the SARS-CoV-2 FSE hairpin. One molecule, which they named compound 5 (C5), decreased the hairpin’s efficiency in helping the virus translate its genes by about 25% in cell culture experiments, reducing the ability of SARS-CoV-2 to make essential proteins. To enhance the potency of C5, the team attached a molecule (called a ribonuclease-targeting chimera, or RIBOTAC) that recruits a human enzyme that degrades the viral RNA. In cultured cells, RIBOTAC increased the potency of C5 by about 10-fold. Although much more work is needed to develop the RIBOTAC-containing compound into a drug, these findings suggest that the SARS-CoV-2 genome can be targeted by small molecules that disrupt its function, the researchers say.
The authors acknowledge funding from the National Institutes of Health.
The paper’s abstract will be available on September 30 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acscentsci.0c00984
The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and its people. The Society is a global leader in providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a specialist in scientific information solutions (including SciFinder® and STN®), its CAS division powers global research, discovery and innovation. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.
To automatically receive news releases from the American Chemical Society, contact [email protected].
MEDIA CONTACTRegister for reporter access to contact details
ACS Central Science