Researchers identify small molecules that target and destroy RNA sequence of SARS-CoV-2
Since the time SARS-CoV-2 was first uncovered in China, various approaches like repurposing old medications, development of vaccine and plasma therapy have been proposed and attempted to prevent this viral infection. Lately, researchers from the Scripps Research Institute, Florida, United States have actually discovered a new method to target as well as destroy the RNA sequence of the SARS-CoV-2 virus that causes COVID-19.
Targeting the hairpin
RNA is a molecule similar to DNA present in human cells. However, RNA has a single strand, unlike DNA. The genetic material of coronavirus is RNA.
The researchers discovered that the RNA of SARS-CoV-2 folds up into various forms, which can quickly be targeted by medicines. Frameshifting element (FSE) – a region of the RNA, has a hairpin-like structure that, together with other structures, assists the virus to translate its genes into proteins, hence causing the spread of the disease.
Researchers thought that if they discover a small-molecule drug that can attach to the hairpin structure and deactivate it, the viral replication will be inhibited.
Dr. Matthew Disney and Dr. Hafeez Haniff with their co-workers started microarray analyses (examining thousands of genes simultaneously) to discover small molecules (a medicine) that can attach to a certain region of the SARS-CoV-2 FSE hairpin structure.
Further, the researchers tested if they could improve the effectiveness of the drug by joining another molecule by which the activity of RNA-destroying cellular enzyme would be enhanced.
Result of the study
The outcomes of the study are released in the journal ACS Central Science.
Researchers discovered a small drug-like molecule called substance 5 (C5), on exploring different molecules. The molecule preferably attaches to the hairpin structure of coronavirus with a Kd of 11 nm. Kd is the device used to identify the binding ability of a molecule. C5 impaired FSE in the cells reduces the hairpin’s gene-translating effectiveness by nearly 25%.
Hence, it minimized the capability of COVID-19 causing coronavirus to form necessary proteins for viral spread.
Researchers attached one more molecule, named ribonuclease-targeting chimera (RIBOTAC), to it for further enhancing the strength of C5. The ribonuclease-targeting chimera obtains a cellular ribonuclease to damage the C5-RIBOTAC (genome of the virus), and transform it into C5-Chem-CLIP, which can immediately target the RNA of the virus.
The study revealed that RIBOTAC enhanced the performance of C5 by nearly 10-fold.
The team inferred that though additional studies are required on this, scientists can develop a medication, utilizing RIBOTAC-containing compounds, to interrupt the function of the coronavirus genome.
Researchers identify small molecules that target and destroy RNA sequence of SARS-CoV-2
Author: Sruthi S
