Small molecule inhibitor found to be effective against SARS-CoV-2 variants HopkinsMedicine SARSCoV2 COVID19 Coronavirus Variant Variants SmallMoleculeInhibitor
By Pooja Toshniwal PahariaSep 12 2022Reviewed by Aimee Molineux In a recent study published in Frontiers in Microbiology, researchers developed RK-33, a small molecule inhibitor of DDX3, and evaluated its efficacy against severe acute respiratory syndrome coronavirus 2 variants of concern .
Plaque assays were performed to assess viral titers, and the median effective concentration values were determined. SARS-CoV-2 RNA extracted from SARS-CoV-2-containing cell lysates was subjected to ribonucleic acid sequencing analysis. In addition, SARS-CoV-2 RNA-dependent RNA polymerase and envelope genes were amplified from RNA by quantitative reverse transcription-polymerase chain reaction analysis to evaluate copy numbers, and proteomic analysis was performed.
Further, proteomic and RNA-seq analyses indicated that RK-33 downregulated most of the SARS-CoV-2 genes [S, E, membrane , nucleocapsid , open reading frames 1ab, 3a,7a, 7b, 8, and 10]. Furthermore, RK-33 reduced transmembrane serine protease 2 expression by 50% within two days, possibly due to DDX3’s ability to unwind G-quadruplex structures that are present in TMPRSS2.
The top five significantly enriched mechanisms post-SARS-CoV-2 infections are interferon-alpha/beta IFN-stimulated gene 15 antiviral mechanisms, SARS-CoV-2 mRNA translation, signal recognition particle -dependent targeting of co-translational proteins to membranes, and elongation of peptide chains.
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Read more »