DeCure for Immunodeficiency 65, susceptibility to viral infections
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 65, susceptibility to viral infections — 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 moduleImmunodeficiency 65, susceptibility to viral infections 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 immunodeficiency 65, susceptibility to viral infections 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.
What the evidence adds up to
In hyper IgE syndrome (HIES), patients with STAT3 mutations lack Th17 cells and develop autosomal dominant HIES, while mutations in DOCK8 are associated with decreased expansion of CD8 T cells and viral infections including molluscum contagiosum. Recurrent mucocutaneous candidiasis has been linked to mutations in CARD9 and DECTIN-1, genes required for production of Th17-driving cytokines. In HIV-positive patients, a decreased Th17:Th1 ratio has been observed, and Th17 cells were preferentially depleted from the gastrointestinal tract within weeks of simian immunodeficiency virus infection in rhesus macaques. One HIV-infected long-term non-progressor with undetectable viral load without antiretroviral therapy showed production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17, but IL-4 was identified, and the authors describe a non-polarized cytokine response of the TH1 and TH2 profiles.
In patients expressing protective HLA-B alleles such as HLA-B*27 and HLA-B*57, the human restriction factor TRIM5α contributes to control of HIV-1 replication. Viruses from HLA-B*57-positive and HLA-B*27-positive patients who spontaneously controlled viral replication showed significantly greater sensitivity to hTRIM5α than viruses from viremic patients expressing these alleles. A significant negative correlation between hTRIM5α sensitivity and viral load was observed. In HLA-B*57-positive patients, the T242N mutation in the TW10 CTL epitope was strongly associated with hTRIM5α sensitivity. In HLA-B*27-positive controllers, hTRIM5α sensitivity was associated with reduced emergence of key CTL mutations. Viral evolution to avoid hTRIM5α sensitivity could be associated with reduced viral replicative capacity.
As of 1995, there was no means to eradicate HIV from the human body, and drug therapy only slowed viral replication, with significant adverse reactions and interactions. A 1986 article on treatment of infections in AIDS patients provides no specific efficacy data.
What is still missing is a trial design that tests whether boosting Th17 responses or manipulating TRIM5α sensitivity can improve viral control in patients who do not spontaneously control HIV, and whether such strategies would be safe and durable. Patient stratification by HLA type and viral capsid sequence would be needed, and funding for such mechanistic studies remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in HIV and AIDS · 2010 · 51 citations · open access
Th17 cells, Jobʼs syndrome and HIV: opportunities for bacterial and fungal infections
AbstractPURPOSE OF REVIEW: Patients with hyper IgE syndrome (HIES) share with HIV patients a predisposition to infections, including candidiasis in autosomal dominant HIES (AD-HIES) and molluscum contagiosum and other viral infections in other disorders of elevated IgE with infectious predilections. This review highlights the underlying pathogenesis of these diseases and their relevance to HIV infection. RECENT FINDINGS: Patients with mutations in STAT3, who lack Th17 cells, develop AD-HIES, whereas other disorders of elevated IgE may be caused by mutations in Tyk2 or DOCK8, the latter of which is associated with decreased expansion of CD8 more so than CD4 T cells. Recent studies on patients with recurrent mucocutaneous candidiasis have led to the discovery of mutations in CARD9 and DECTIN-1, genes key to the production of the Th17-driving cytokines IL-1beta, IL-6, and IL-23. Studies of the peripheral blood of HIV-positive patients have shown a decreased Th17:Th1 ratio, and Th17 cells were preferentially depleted from the gastrointestinal tract within weeks of simian immunodeficiency virus infection in rhesus macaques. SUMMARY: The consequences of inadequate Th17 production in primary immunodeficiency syndromes illustrate the role of Th17 cells in controlling pathogens to which HIV-positive individuals are susceptible. Further understanding of the pathogenesis of opportunistic disease in HIV infection will probably require exploring the role of Th17 cells.
Journal of Virology · 2013 · 26 citations · open access
Pressure from TRIM5α Contributes to Control of HIV-1 Replication by Individuals Expressing Protective HLA-B Alleles
AbstractThe expression of certain HLA class I alleles, including HLA-B*27 and HLA-B*57, is associated with better control of human immunodeficiency virus type 1 (HIV-1) infection, but the mechanisms responsible are not fully understood. We sought evidence that pressure from the human restriction factor TRIM5α (hTRIM5α) could contribute to viral control. The hTRIM5α sensitivity of viruses from both HLA-B*57-positive (HLA-B*57(+)) and HLA-B*27(+) patients who spontaneously controlled viral replication, but not viruses from viremic patients expressing these alleles, was significantly greater than that of viruses from patients not expressing these protective HLA-B alleles. Overall, a significant negative correlation between hTRIM5α sensitivity and viral load was observed. In HLA-B*57(+) patients, the T242N mutation in the HLA-B*57-restricted TW10 CD8(+) T lymphocyte (CTL) epitope was strongly associated with hTRIM5α sensitivity. In HLA-B*27(+) controllers, hTRIM5α sensitivity was associated with a significant reduction in emergence of key CTL mutations. In several patients, viral evolution to avoid hTRIM5α sensitivity was observed but could be associated with reduced viral replicative capacity. Thus, in individuals expressing protective HLA-B alleles, the combined pressures exerted by CTL, hTRIM5α, and capsid structural constraints can prevent viral escape both by impeding the selection of necessary resistance/compensatory mutations and forcing the selection of escape mutations that increase hTRIM5α sensitivity or impair viral replicative capacity.
The Brazilian Journal of Infectious Diseases · 2018 · 7 citations · open access
Non-polarized cytokine profile of a long-term non-progressor HIV infected patient
AbstractThe HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles.
Journal of the American Podiatric Medical Association · 1995 · 2 citations
Guide to medications used to treat acquired immune deficiency syndrome
AbstractCurrently, there is no means to eradicate the human immunodeficiency virus (HIV) from the human body. Thus, drug therapy provides an important mechanism to slow viral replication and its damaging effects on the body. A review of the drugs used in the care of the patient with acquired immune deficiency syndrome (AIDS) is provided, which highlights the significant adverse reactions and interactions associated with their use.
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.
