DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for fungal infectious disease — screening already-approved drugs against its 32-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFungal infectious disease maps to a 32-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 fungal infectious disease 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
dihydrofolate reductase (DHFR) — DHFR 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4M6J · 1.201 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
Fungal infections have become more severe over the past three decades, killing more than 1.6 million people each year. Candida species are a common cause of invasive fungal infections, and widespread use of antifungals has led to drug resistance, creating a need for cost-effective alternatives. Drug repurposing has been studied as a way to identify new antimycotic treatments more quickly and on a lower budget. A 2024 review compiled literature on repurposed drugs tested against clinical isolates of Candida and other fungal pathogens, aiming to illustrate the role of repurposing in treating candidiasis.
In solid organ transplant patients, opportunistic fungal infections are a frequent life-threatening complication. The incidence ranges from 2% to 50% depending on the organ transplanted, with kidney recipients having the lowest rate and liver recipients the highest. New antifungal medications and immunosuppressants have changed the spectrum of treatment and prevention, but prompt recognition and treatment remain imperative. The review noted that further advances in early detection and less toxic medications are needed.
A 2001 review explained that few fungi are professional pathogens, and their pathogenic mechanisms are highly complex, arising from adaptations of pre-existing traits from nonparasitic lifestyles. Genetic approaches had elucidated many fungal virulence factors, and knowledge of host reactions had also clarified much about fungal disease. That review was aimed at fungal geneticists, molecular biologists, and physicians, and did not attempt comprehensive coverage of fungal disease.
What is still missing are large-scale clinical trials of specific repurposed drugs against defined Candida or other fungal isolates, funding to move candidate drugs beyond in vitro and preclinical work, and better patient stratification in transplant and immunocompromised populations to identify who might benefit from repurposed agents.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Ophthalmology · 2008 · 263 citations
Voriconazole in the treatment of fungal eye infections: a review of current literature
AbstractAtherosclerotic renovascular disease (ARVD) is associated with heart disease. There has been no systematic study of cardiac structure and function in patients with this condition. In this study, the epidemiology of cardiac changes and their relationship to renal function, renovascular anatomy, and BP are delineated. With the use of a cross-sectional design, 79 patients with ARVD and 50 control patients without ARVD underwent echocardiography and 24-h ambulatory BP monitoring. Clinical and biochemical data were collected. Results were analyzed according to renal function, residual renal artery patency, and unilateral or bilateral ARVD. Only 4 (5.1%) patients with ARVD had normal cardiac structure and function. Patients with ARVD (age 70.7 ± 7.5 yr; estimated GFR 36 ± 19 ml/min) had significantly more cardiovascular comorbidity (77.2 <i>versus</i> 42.0%; <i>P</i> < 0.001), greater prevalence of left ventricular (LV) hypertrophy (78.5 <i>versus</i> 46.0%; <i>P</i> < 0.001) and LV diastolic dysfunction (74.6 <i>versus</i> 40.0%; <i>P</i> < 0.001), and greater LV mass index (183 ± 74 <i>versus</i> 116 ± 33 g/m<sup>2</sup>; <i>P</i> < 0.001) and LV end-diastolic volume index (82 ± 35 <i>versus</i> 34 ± 16 ml/m<sup>2</sup>; <i>P</i> < 0.001) than control subjects. BP was similar for both patient groups. For patients with ARVD, neither renal function nor renal artery patency predicted a difference in echocardiographic or ambulatory BP monitoring parameters. Patients with bilateral ARVD had greater LV mass index and LV dilation than patients with unilateral disease. Patients with ARVD exhibit a high prevalence of cardiac morphologic and functional abnormalities at early stages of renal dysfunction. Such patients must be identified early in their disease course to allow risk factor modification.
Annual Review of Microbiology · 2001 · 174 citations
Aspects of Fungal Pathogenesis in Humans
AbstractFungal diseases have become increasingly important in the past few years. Because few fungi are professional pathogens, fungal pathogenic mechanisms tend to be highly complex, arising in large part from adaptations of preexisting characteristics of the organisms' nonparasitic lifestyles. In the past few years, genetic approaches have elucidated many fungal virulence factors, and increasing knowledge of host reactions has also clarified much about fungal diseases. The literature on fungal pathogenesis has grown correspondingly; this review, therefore, will not attempt to provide comprehensive coverage of fungal disease but focuses on properties of the infecting fungus and interactions with the host. These topics have been chosen to make the review most useful to two kinds of readers: fungal geneticists and molecular biologists who are interested in learning about the biological problems posed by infectious diseases, and physicians who want to know the kinds of basic approaches available to study fungal virulence.
Fungal Infections in Solid Organ Transplant Patients
AbstractBACKGROUND: Solid organ transplantation is becoming increasingly more common in the treatment of end-stage organ failure. Opportunistic fungal infections are a frequent life-threatening complication of transplantation. MATERIALS AND METHODS: In this article, a review of the infections in the different organ transplant recipients is presented. RESULTS: The incidence of fungal infections in organ transplant patients ranges from 2% to 50% depending on the type of organ transplanted, kidney recipients being the least frequent and liver recipients having the highest rate of infection. New antifungal medications and immunosuppressants have changed the spectrum of fungal treatment and prevention. CONCLUSION: Prompt recognition and treatment of infection is imperative for successful therapy. Further advancements in early detection and the development of less toxic medications will lead to refinements in the treatment of fungal infections.
Journal of Paediatrics and Child Health · 2003 · 32 citations · open access
SEVERE VINCRISTINE NEUROTOXICITY WITH CONCOMITANT USE OF ITRACONAZOLE
Abstract30 June 2003 Dear Editor, SEVERE VINCRISTINE NEUROTOXICITY WITH CONCOMITANT USE OF ITRACONAZOLE We would like to share our experience of severe itraconazole− vincristine interaction which emphasizes the need to use this particular antifungal agent with caution when co-administering vincristine to patients. Itraconazole, with its broad-spectrum of antifungal activity, is often prescribed for childhood cancer patients for both treatment and prophylaxis of fungal infections. However, many of the chemotherapy protocols that these children are treated with, especially for lymphoid malignancies, also include the vinca alkaloid, vincristine. Our first patient was an 8-year-old boy with T-cell acute lymphoblastic leukemia (ALL) who was receiving induction therapy with oral dexamethasone and weekly intravenous vincristine (1.5 mg/m2). Concomitantly, he received prophylactic itraconazole (5 mg/kg per day) as there had been a recent rise in the incidence of fungal infections in our unit. This was believed to be related to major building and earth works being carried out in the vicinity of the hospital. Four days after the third dose of vincristine, he presented with bilateral ptosis and paralytic ileus. Twenty-four hours after the onset of the initial symptoms, he developed generalized tonic-clonic seizures with progression to status epilepticus. Examination of the cerebrospinal fluid (CSF) and computerized tomography of the brain were normal. Serum sodium at this time was 120 mmol/L and serum osmolarity was 205 mosm/L, suggesting a syndrome of inappropriate antidiuretic hormone secretion (SIADH) as the cause of severe hyponatremia. He required assisted ventilation for 72 h and the seizures were controlled with phenytoin. The combination of neuro-toxicity and SIADH pointed to vincristine toxicity, which was likely to have been aggravated by co-administration of itraconazole. Following cessation of itraconazole and reduction in the subsequent doses of vincristine, the SIADH resolved after 2 weeks while the bilateral ptosis resolved 3 weeks thereafter. The second patient was a 2-year-old boy with precursor B-cell ALL who was also started on prophylactic itraconazole with the commencement of induction chemotherapy. After the second weekly dose of vincristine (1.5 mg/m2), he presented with severe abdominal pain associated with abdominal distension and absent bowel sounds. He was diagnosed as having vincristine-induced ileus. This improved after 8 days with conservative measures. He was then deemed well enough to receive the third dose of vincristine. The itraconazole was not stopped. Unfortunately, 2 days after receiving the vincristine, he returned with inability to walk and to pass urine. Clinical examination revealed bilateral lower limb weakness grade 2/5, areflexia, a palpable bladder and reduced anal tone. An urgent magnetic resonance imaging (MRI) scan ruled out a spinal cord lesion. However, the MRI scan of the brain showed bilateral symmetrical demyelinating changes in the parietal and occipital areas. This was thought to be consistent with vincristine neurotoxicity and this diagnosis was further supported by the electromyography findings, which showed electrophysiological evidence of sensorimotor peripheral neuropathy. Examination of the CSF was normal. Itraconazole was stopped and the remaining two doses of vincristine were omitted. The paraparesis and bladder control improved over the following 4 weeks. Although vincristine neurotoxicity is not an unknown entity1, such side effects are unusual with the cumulative doses administered to both these patients (5 mg in patient 1 and 2.7 mg in patient 2). The most likely explanation is the co-administration of itraconazole, which blocks the CYP3A subfamily of hepatic cytochrome P450 enzymes which then leads to the consequent delay in the metabolism of vincristine. In addition, itraconazole inhibits the P-glycoprotein efflux transport pump of the cells, resulting in high intracellular vincristine levels2. Clinicians administering chemotherapy need to be aware of the interaction between vincristine and itraconazole, where even a single dose can lead to severe toxicity3−5. Although previous reports of itraconazole interaction have only involved vincristine, it is reasonable to assume that all vinca alkaloids interact in the same manner because they share similar metabolism pathways. We agree with the recommendation that prophylactic itraconazole be interrupted during the time of vincristine administration to minimize the incidence and/or severity of neurotoxicity which in turn leads to the omission of scheduled vincristine doses and deviation from the treatment protocol.
Effectiveness of drug repurposing approach against Candida isolates
AbstractOver the past three decades, there has been an increase in the severity of fungal infections, affecting several individuals and claiming the lives of more than 1.6 million people every year. Species of Candida are one of the causatives of invasive fungal infections, and the extensive use of antifungals for their treatment has led to the emergence of drug resistance in these species, highlighting the need for the exploration of effective and cost-effective therapeutics. Drug repurposing is an important solution for alternative therapeutics. There are many studies where antifungal indications of any existing drug have been analyzed with an aim to establish new antimycotic therapeutics in a short time and with a lower budget. In this review, efforts are made to compile the literature on repurposed drugs against clinical isolates of Candida and fungal pathogens to better illustrate drug repurposing's role in the treatment of candidiasis.
Zenodo (CERN European Organization for Nuclear Research) · 2023 · 0 citations · open access
NEW APPROACHESTO TREATMENT OF FUNGAL INFECTIONS AT WOMEN
AbstractThe article reflects the main problems of diagnosis and treatment of patients with vulvovaginal candidiasis (VVC). Data on the effectiveness of the broad-spectrum antimycotic drug fenticonazole in the treatment of VVC are presented, which makes it possible to increase the effectiveness of treatment and reduce the frequency of relapses of the disease.
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.
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