ArticleFrontiers in microbiology2022
RK-33, a small molecule inhibitor of host RNA helicase DDX3, suppresses multiple variants of SARS-CoV-2.
Article in Frontiers in microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Spatially Constrained Monte Carlo Permutation Test Reveals Diffusion Changes Near Stress Granules.bioRxiv : the preprint server for biology · 2026Article
- A pan-viral map of host dependency factors from multi-omics integration and machine learning across influenza A, SARS-CoV-2, Zika, and dengue viruses.Journal of translational medicine · 2026Article
- RK-33 inhibits the OC43 coronavirus and induces stress granules via DDX3X-independent mechanisms.RNA (New York, N.Y.) · 2026Article
- RNA helicase DDX3X promotes NK cell survival by supporting MCL1 expression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- DDX3X/MAVS alleviates doxorubicin‑induced cardiotoxicity by regulating stress granules.Molecular medicine reports · 2025Article
- DEAD-Box Helicase 3 Modulates the Non-Coding RNA Pool in Ribonucleoprotein Condensates During Stress Granule Formation.Non-coding RNA · 2025Article
- Repurposing Biomolecules fromInternational journal of molecular sciences · 2025Article
- Current perspectives in drug targeting intrinsically disordered proteins and biomolecular condensates.BMC biology · 2025Review
- DDX3X and virus interactions: functional diversity and antiviral strategies.Frontiers in microbiology · 2025Review
- Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity.Immunological reviews · 2025Review
- DDX3X Promotes Rotavirus Infection and Serves as an Antiviral Target.Transboundary and emerging diseases · 2025Article
- The DEAD-box RNA helicase 27 negatively regulates the replication of porcine reproductive and respiratory syndrome virus by mediating GP2a autophagy degradation and inducing interferon-β production.Frontiers in immunology · 2025Article
- SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA.PLoS pathogens · 2024Article
- Prokaryotic Expression and Affinity Purification of DDX3 Protein.Protein and peptide letters · 2024Article
- Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA.International journal of molecular sciences · 2023Article
- In Silico Binding of 2-Aminocyclobutanones to SARS-CoV-2 Nsp13 Helicase and Demonstration of Antiviral Activity.International journal of molecular sciences · 2023Article
- Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells.iScience · 2023Article
- Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19.International journal of molecular sciences · 2022Review
- The multifaceted roles of NLRP3-modulating proteins in virus infection.Frontiers in immunology · 2022Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
SARS-CoV-2, the virus behind the deadly COVID-19 pandemic, continues to spread globally even as vaccine strategies are proving effective in preventing hospitalizations and deaths. However, evolving variants of the virus appear to be more transmissive and vaccine efficacy toward them is waning. As a result, SARS-CoV-2 will continue to have a deadly impact on public health into the foreseeable future. One strategy to bypass the continuing problem of newer variants is to target host proteins required for viral replication. We have used this host-targeted antiviral (HTA) strategy that targets DDX3X (DDX3), a host DEAD-box RNA helicase that is usurped by SARS-CoV-2 for virus production. We demonstrated that targeting DDX3 with RK-33, a small molecule inhibitor, reduced the viral load in four isolates of SARS-CoV-2 (Lineage A, and Lineage B Alpha, Beta, and Delta variants) by one to three log orders in Calu-3 cells. Furthermore, proteomics and RNA-seq analyses indicated that most SARS-CoV-2 genes were downregulated by RK-33 treatment. Also, we show that the use of RK-33 decreases TMPRSS2 expression, which may be due to DDX3s ability to unwind G-quadraplex structures present in the TMPRSS2 promoter. The data presented support the use of RK-33 as an HTA strategy to control SARS-CoV-2 infection, irrespective of its mutational status, in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.