DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for endocarditis — screening already-approved drugs against its 20-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEndocarditis maps to a 20-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 endocarditis 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
protein tyrosine phosphatase receptor type D (PTPRD) — PTPRD 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 flcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2YD6 · 1.35 Å · ligand CITRATE ANION (FLC). Experimental structure, not a prediction.
What the evidence adds up to
Twenty-nine patients with penicillin-resistant viridans group streptococci endocarditis were identified at the Mayo Clinic over 38.5 years. Nineteen of 19 native valve patients were cured; nine received a 2.3-week regimen of penicillin plus an aminoglycoside, and eight received 5.1-week courses of either a penicillin or ceftriaxone combined with an aminoglycoside, or ceftriaxone alone. Nine of 10 prosthetic valve patients were cured with 4.1-week regimens of vancomycin or ceftriaxone, alone or in combination. Mean follow-up was 9.1 years. The authors concluded that existing treatment guidelines should work for most patients.
A case series of 12 endocarditis patients treated with ceftobiprole reported a cure rate of 83% (10 of 12). Eleven of the 12 received ceftobiprole in combination with daptomycin; one received ceftobiprole alone. In 9 of 12 cases, ceftobiprole was started after a previous antibiotic regimen had failed. In three patients with persistently positive blood cultures, bacteraemia cleared rapidly after ceftobiprole was given. All 12 patients had Gram-positive infections; three were polymicrobial. The authors called ceftobiprole a promising alternative, especially in combination.
A study of 76 patients with definite infective endocarditis (mean age 26 years) measured soluble adhesion molecules. Thirteen patients (17.1%) had embolic events. Vegetations were larger in patients with emboli (1.4 cm vs 1.0 cm, p=0.03), but the presence of vegetations did not differ significantly between groups. Mean plasma P-selectin was 58.69 ng/ml in patients with emboli versus 29.65 ng/ml in those without and 25.82 ng/ml in controls (p<0.001 for both comparisons). Mean E-selectin was 73.15 ng/ml in the emboli group versus 42.84 ng/ml in the non-emboli group and 34.23 ng/ml in controls (p<0.001). The authors suggested these molecules might identify patients at high thromboembolic risk.
A 1997 surgical paper on the Ross operation for aortic valve endocarditis argued that prospective randomised trials are virtually impossible in this setting because of small patient numbers and many variables, and that the surgical challenge is often extreme. No patient data or outcomes were reported in that abstract.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Infective Endocarditis Due to Penicillin-Resistant Viridans Group Streptococci
AbstractBACKGROUND: The emergence of viridans group streptococci that are relatively or fully resistant to penicillin is increasingly being recognized worldwide, but only a scant number of penicillin-resistant isolates have been described as a cause of infective endocarditis. Because of the paucity of data, it has been difficult to define optimal treatment regimens for this syndrome. Thus, recommendations for therapy have largely been made on the basis of consensus opinion. METHODS: We retrospectively identified a cohort of patients with infective endocarditis due to penicillin-resistant viridans group streptococci who were seen at the Mayo Clinic (Rochester, MN) between January 1967 and April 2006. Demographic characteristics, clinical features, treatment regimens, and outcomes were analyzed. Mean values are shown with standard deviations. RESULTS: Twenty-nine patients were identified over the 38.5-year study period. Nineteen patients with native valve endocarditis were cured; 9 of these 19 patients received a 2.3+/-0.4-week antibiotic regimen consisting of penicillin and an aminoglycoside, and 8 of these 19 patients received treatment courses of 5.1+/-1.4 weeks' duration that consisted of either a bimodal combination regimen with a penicillin or ceftriaxone and an aminoglycoside or ceftriaxone monotherapy. Nine of 10 patients with prosthetic valve infection were cured with 4.1+/-0.6-week regimens that consisted of either a combination regimen or monotherapy with vancomycin or ceftriaxone. Mean duration of follow-up after hospital discharge was 9.1 years. CONCLUSIONS: Outcomes of this relatively large population of patients with endocarditis with a prolonged duration of follow-up indicate that the application of current treatment guidelines should be successful in most patients.
Journal of Global Antimicrobial Resistance · 2019 · 37 citations · open access
Ceftobiprole for the treatment of infective endocarditis: A case series
AbstractOBJECTIVES: Ceftobiprole is a relatively new cephalosporin with broad-spectrum activity and good tolerability. Despite its promising characteristics, to our knowledge, only two case reports, previously published also by some of us, is available concerning its administration for the treatment of infective endocarditis. Hereby we report our experience in this field. METHODS: All the patients with infective endocarditis treated with ceftobiprole were enrolled. RESULTS: 12 cases of endocarditis were treated with ceftobiprole, 11/12 in combination with daptomycin and 1/12 as monotherapy. Gram-positive bacteria were isolated in 12/12 patients; 3 cases were polymicrobial. Cure rate was 83% (10/12 patients). In 9/12 (75%) cases, patients were switched to ceftobiprole following failure of previous antimicrobial regimen. In 3/3 patients in which ceftobiprole was administered because of persistently positive blood culture, bacteraemia clearance was rapidly achieved. CONCLUSIONS: Ceftobiprole, especially in combination, could be a promising alternative treatment for infective endocarditis.
Increased levels of soluble adhesion molecules, E-selectin and P-selectin, in patients with infective endocarditis and embolic events
AbstractAIMS: Inflammation-induced procoagulant changes and endothelial cell activation appear to play an important role in thromboembolic complications of infective endocarditis. Hence, the aim of this study was to compare the plasma levels of soluble adhesion molecules E- and P-selectin in infective endocarditis patients with and without embolic events, and healthy subjects. METHODS AND RESULTS: The study group consisted of 76 consecutive patients (mean age=26 years old, range from 8 to 64 years) with definite infective endocarditis according to the Duke criteria. Thirteen of the patients (17.1%) had embolic events. Transoesophageal echocardiographic examinations were performed on all patients within 3 days of initiation of antimicrobial therapy. Although there was a trend towards a higher rate of vegetations detected in those with embolic events than in those without, this did not reach statistical significance (84.6% vs 80.9%, P>0.05). Significantly larger vegetations were observed in patients with embolic events as compared to those without embolic events (1.4 cm vs 1.0 cm, P=0.03). The mean plasma concentrations of P-selectin were elevated in patients with embolic events as compared to both patients without embolic events and control subjects (58.69+/-7.49 ng x ml(-1)vs 29.65+/-5.69 ng x ml(-1), P=<0.001 and 58.69+/- 7.49 ng x ml(-1) vs 25.82+/-5.38 ng x ml(-1), P<0.001). Similarly, the patients with embolic events had increased plasma levels of E-selectin compared to those without embolic events and the control group (73.15+/-11.47 ng x ml(-1) vs 42.84+/-8.77 ng x ml(-1), P<0.001 and 73.15+/- 11.47 ng x ml(-1) vs 34.23+/-5.92 ng x ml(-1), P<0.001). CONCLUSION: Determination of these membrane activation molecules may provide useful markers with which to identify patients at high thromboembolic risk from infective endocarditis.
Treatment of aortic valve endocarditis with the Ross operation
AbstractEradication of advanced endocarditis requires complete debridement of all infected and non-viable tissue and successful reconstruction of the heart. Many treatment strategies have been proposed, but because of the relatively small number of patients in each series and the large number of variables, it is virtually impossible to make a strict scientific evaluation of the alternatives, nor can help be expected from prospective, randomized trials in the future. Deciding on a treatment strategy can, in and of itself, be difficult, but thought must be followed by action, and the surgical challenge in these patients is often extreme.
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.
