Up till now, the COVID-19 has spread through 216 countries, affecting more than 48.1 million individuals around the world.
By Abeer Fatima and Safana Khurram
With the rise of the pandemic across the entire world we’ve all experienced lockdown or more famously known as ‘quarantine’. The cause of this is what commonly is known as the Coronavirus disease or COVID-19 and in biological terms as SARS-CoV-2 virus. The COVID-19 cases started to decrease but now WHO warns the world with the threat of second upcoming wave of Coronavirus. Is there a cure? What are scientists doing, when will a vaccine be created? When will Corona be over? These are questions that have crossed the mind of everyone at least once. Recently, Scripps Research Chemist Matthew Disney and his colleagues have found a small molecule that can reportedly stop the spread of SARS-CoV-2 virus. To understand the research conducted by them, let us first know what SARS-CoV-2 virus actually is?
Viruses are microscopic infection causing agents, which cannot reproduce on their own so they have to take over the system of another living cell. For their division, viruses possess an instruction material known as genome or genetic material (DNA or RNA).
SARS-CoV-2 virus uses RNA as its genetic material. When this virus enters the human body, it releases its RNA into human cells, and this RNA takes over the cell. It starts the production of its own proteins with the help of human protein-producing organelles known as ribosomes.
A phenomenon called Ribosomal Frameshifting enables a virus to generate multiple types of proteins using the same piece of RNA again and again and generate copies of itself. This frameshifting is a highly controlled, programmed strategy used by the SARS-CoV-2 virus to produce proteins essential for its survival. A specific region on its viral RNA called the Frameshifting Element (FSE), contains a hairpin-shaped and other structures that help the virus to translate its genetic material into proteins. These unique shapes can potentially be targeted by drugs.
Demonstration of a hairpin-shaped structure formed by RNA.
Researchers studied a collection of RNA-focused small molecular drugs. They identified three molecules that have the ability to bind to the hairpin structure of SARS-CoV-2 viral RNA. Out of these three, the C5 molecule was most effective in a dose-dependent manner, i.e. its effect changes when the dose of the drug is changed. Attachment of C5 with FSE decreased the RNA hairpin’s efficiency by about 25% in cell culture experiments. This eventually leads to reduction in the ability of SARS-CoV-2 to make essential proteins.
To enhance the potency of C5, the researchers’ team attached a molecule called RIBOTAC (Ribonuclease-Targeting Chimera) that restores a human enzyme which breaks down the viral RNA. It was observed that RIBOTAC increased the effectiveness of C5 molecules by about 10-fold. C5-RIBOTAC complex is also specific in its function, i.e. it only affects viral RNA and cannot harm host (human) RNA.
C5-RIBOTAC complex inhibits protein formation from SARS-CoV-2 RNA more effectively than the C5 molecule alone.
Collectively, these studies demonstrate that the SARS-CoV-2 RNA should be considered druggable. C5-RIBOTAC complex can prove to be a potential drug against this deadly virus. Researchers are now working on techniques to put forward it in the form of a medicinal drug. This drug can attack the virus when introduced in the human body and be able to administer a cure. Much research is still required and further study will eventually lead to more information on how to combat the virus.
Reference:
“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. https://doi.org/10.1021/acscentsci.0c00984
Authors: Abeer Fatima and Safana Khurram (2020)-Students of Kinnaird College for Women University, Lahore. BS Biotechnology (Semester 3)