AI Article Synopsis
- The discovery of a guanine quadruplex in the TMPRSS2 mRNA could lead to innovative anticancer and antiviral treatments, as TMPRSS2 is linked to both cancer and respiratory viral infections like SARS-CoV-2.
- TMPRSS2 facilitates virus entry into cells by aiding membrane fusion through its proteolytic activity, making it a significant target for therapeutic strategies.
- An experimental-computational approach has resolved the first atomic-level structure of the guanine quadruplex in TMPRSS2 RNA, revealing a rigid core and flexible loop, crucial for developing targeted ligands.
Article Abstract
The presence of a guanine quadruplex in the opening reading frame of the messenger RNA coding for the transmembrane serine protease 2 (TMPRSS2) may pave the way to original anticancer and host-oriented antiviral strategy. Indeed, TMPRSS2 in addition to being overexpressed in different cancer types, is also related to the infection of respiratory viruses, including SARS-CoV-2, by promoting the cellular and viral membrane fusion through its proteolytic activity. The design of selective ligands targeting TMPRSS2 messenger RNA requires a detailed knowledge, at atomic level, of its structure. Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653239 | PMC |
| http://dx.doi.org/10.1002/chem.202403572 | DOI Listing |
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