DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for rubella — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRubella maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for rubella is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
SET and MYND domain containing 3 (SMYD3) — SMYD3 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet samdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6P7Z · 1.19 Å · ligand S-ADENOSYLMETHIONINE (SAM). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 study tested a compound called chalcone (4-ethoxy-2-hydroxy-4,6-dimethoxy-chalcone) against rubella virus in tissue and organ culture. The compound was relatively non-toxic to cells at 8 µg/ml or less. A concentration of 0.03 µg/ml or more inhibited 100 TCID50 of rubella virus. The therapeutic index, defined as the ratio of the maximum tolerated dose to the minimum effective dose, was greater than 70. The authors state that if used in man this compound would have no side effect. No human data exist.
A 2009 study of 714 healthy children who received two age-appropriate doses of rubella-containing vaccine found that polymorphisms in the vitamin A receptor, retinoic acid-inducible gene I (RIG-I), and tripartite motif 5 and 22 (TRIM5 and TRIM22) genes were significantly associated with rubella vaccine antibody response. The minor allele of rs4416353 in the vitamin A receptor gene was associated with an allele dose-related decrease in rubella antibody response (P = .019). The minor variant of nonsynonymous SNP rs10813831 (Arg7Cys) in the RIG-I gene was associated with an allele dose-related decrease in rubella antibody level from 37.4 to 28.0 IU/mL (P = .035). Increased representation of the minor allele of the 5'UTR SNP rs3824949 in the TRIM5 gene was associated with an allele dose-related increase in rubella antibody (P = .015). These findings expand immunogenetic understanding of vaccine-induced immunity but do not address treatment of infection.
A 2022 study developed an improved multiplex RT-qPCR for detecting rubella viral RNA by targeting the 5' terminus of the genome, which is more conserved than the commonly used E1 protein coding region. The new method had a limit of detection of four copies of rubella RNA per reaction with high specificity. Concordance between the new method and the current method, based on testing 251 clinical specimens from a rubella outbreak, was 99.4%. When 62 rubella IgM positive serum samples from an outbreak were tested, eleven tested positive using the multiplex method while none were positive using the method targeting E1. This assay improves detection for molecular surveillance and case confirmation but is a diagnostic tool, not a treatment.
A 2022 study examined the roles of rubella virus nonstructural proteins P150 and P90 in replication complex assembly and fiber formation. The precursor P200 was required for initial targeting to cytoplasmic foci. P150 was the determinant of fiber formation, and an alpha-helix at the N-terminus of P150 was important for correct targeting of P200. The membrane binding domain was within the N-terminal ~450 amino acids of P150. Fiber formation relied on an intact microtubule network, but microtubules were not necessary for rubella virus replication. P150 fibers were not required for replication but appeared important for formation of cytoplasmic extensions through which cell-to-cell transport of viral RNA in the absence of virus particles occurs. This work clarifies basic virology but does not identify a therapeutic target.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Infectious Diseases · 2009 · 63 citations · open access
Polymorphisms in the Vitamin A Receptor and Innate Immunity Genes Influence the Antibody Response to Rubella Vaccination
AbstractBACKGROUND: Genetic polymorphisms play an important role in rubella vaccine-induced immunity. METHODS: We genotyped 714 healthy children after 2 age-appropriate doses of rubella-containing vaccine for 142 potential single-nucleotide polymorphisms (SNPs). RESULTS: Specific polymorphisms in the vitamin A receptor, retinoic acid-inducible gene I (RIG-I), and tripartite motif 5 and 22 (TRIM5 and TRIM22) genes were significantly associated with rubella vaccine humoral immunity. The minor allele of the rs4416353 in the vitamin A receptor gene was associated with an allele dose-related decrease (P = .019) in rubella antibody response. The minor allele of rs6793694, in the vitamin A receptor gene, was associated with an allele dose-related antibody decrease (p = .039). The minor variant of nonsynonymous SNP rs10813831 (Arg7Cys) in the RIG-I gene was associated with an allele dose-related decrease in rubella antibody level from 37.4 to 28.0 IU/mL (P = .035), whereas increased representation of the minor allele of the 5'UTR SNP (rs3824949, P = .015) in the antiretroviral TRIM5 gene was associated with an allele dose-related increase in rubella antibody. It is of particular interest that the nonsynonymous SNP rs3740996 (His43Tyr) in the TRIM5 gene was associated with variations in rubella antibody response (P = .016) after having been previously found to play a significant functional role. CONCLUSIONS: These findings further expand our immunogenetic understanding of mechanisms of rubella vaccine-induced immunity.
Journal of Virological Methods · 2022 · 6 citations · open access
Improved diagnostic and multiplex RT-qPCR for detecting rubella viral RNA
AbstractAn examination of the nucleic acid sequence alignment of 48 full-length rubella virus genomes revealed that the 5' terminus of the genome is more conserved than the commonly used detection windows for rubella virus RNA located in the E1 protein coding region, suggesting that the 5' terminus could be a target for improving detection of all rubella virus genotypes. Two candidate primer sets were tested and the window between nucleotides (nts) 98 and 251 was found to have the greatest analytical sensitivity for detection of different genotypes. The new method had a limit of detection of four copies of rubella RNA per reaction with high specificity. The average coefficient variation of Ct was 2.2%. Concordance between the new method and currently used method, based on testing 251 clinical specimens collected from a rubella outbreak, was 99.4%. The assay was further improved upon by the incorporation of detection of both rubella virus RNA and mRNA from a cellular reference gene in a multiplex format. The multiplex format did not reduce the sensitivity or the reproducibility of rubella RNA detection and, of 60 specimens tested, the concordance between the single target and multiplex assays was 85.0%. To assess the utility of the multiplex assay for molecular surveillance, 62 rubella IgM positive serum samples from a rubella outbreak were tested, and eleven tested positive using the multiplex method while none were positive using the method targeting E1. These results show that the assay based on the new detection window near the 5' terminus of the genome can improve the detection of rubella virus for the purpose of molecular surveillance and case confirmation, with the added benefit of improved efficiency due to multiplexing.
The antiviral activity of the compound chalcone (4-ethoxy-2-hydroxy-4, 6-dimethoxy-chalcone) against rubella virus in vitro
AbstractThe studies on the antiviral compound chalcone in vitro in both tissue and organ culture systems against rubella virus glass that this compound relatively non toxic to the cell culture and organ culture of the concentration of 8 ug/ml or less, chalcone have significantly antiviral activity against rubella virus in tissue culture and organ culture. We find that a concentration of 0.03ug/ml or more inhibit the IOOTCID50 of rubella virus. The therapeutic index (TI) used in this study to evaluate the drug, the (TI) which is the ratio of the dose of drug which is just toxic (Maximum tolerated dose) to the dose which is just effective (Minimum effective dose). If this index is one or less it not possible to use the drug under the conditions outlined without causing side effect, if the index is larger than the margin of safety is accordingly great, the TI of chalcone against rubella virus more than 70, therefore this compound if used in man have no side effect .
Annals of the New York Academy of Sciences · 2022 · 0 citations · open access
Defining the Role of Rubella Virus Nonstructural Proteins in Replication Complex Assembly and Fiber Formation
AbstractRubella virus (RUBV) is a positive-strand RNA virus and the causative agent of rubella and congenital rubella syndrome in humans. To replicate its RNA, RUBV forms membrane-associated spherules, called replication complexes (RCs), the induction of which requires the two virus nonstructural proteins (NSPs), P150 and P90. Interestingly, late in infection the NSPs form a unique cytoplasmic fiber network, similar in appearance to microtubules, the function of which is unknown. Little is known about the roles of the RUBV NSPs in forming these structures and, to this end, we scrutinized the behavior and biochemical properties of the NSPs, both after expression from plasmids and during RUBV infection, using mutagenic, biochemical and pharmacological approaches. The following findings were made: First, the precursor from which P150 and P90 are produced via an embedded protease at the C-terminus of P150, called P200, was required for initial targeting to cytoplasmic foci. P150 was the determinant of fiber formation and while P90 had no specific targeting sequences on its own, P90 sequences within P200 were required for correct targeting of P200. An alpha-helix at the N-terminus of P150 was also important for correct targeting of P200, putatively by mediating the interaction between P150 and P90 within the precursor. Second, the membrane binding domain within the NSPs was within the N-terminal ~450 amino acids of P150. P150 is in an exceptionally tight association with membranes. Third, both the N- and C-terminal regions of P150, and specifically long alpha-helices within these regions, are necessary for fiber formation. Fiber formation relied on an intact microtubule network, but neither microtubule repositioning nor dynamic movement along microtubules was required. Additionally, it was shown that microtubules were not necessary in RUBV replication. Finally, P150 fibers were not required for RUBV replication; however, it was shown that the fibers are likely important in formation of cytoplasmic extensions through which a novel system of cell-to-cell transport of viral RNA in the absence of virus particles appears to occur.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
