DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for chickenpox — 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 moduleChickenpox 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 chickenpox 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
The live-attenuated varicella vaccine, developed in 1974, reduces chickenpox burden. A 2022 study identified a variant allele in glycoprotein B (gB) selected during vaccine generation that contributes to attenuation. This variant is impaired for fusion, virus entry into neurons from nerve terminals, and replication in human skin cells. The molecular basis for the vaccine's attenuation is otherwise still not well understood.
A 1994 case report describes a young man with non-Hodgkin's lymphoma who suffered multiple discrete relapses of chickenpox each time acyclovir therapy was stopped. His cutaneous infection eventually became unremitting despite continuous acyclovir, with no evidence of visceral dissemination. The patient died suddenly; cause of death was not determined. A 2012 study of 120 hospitalised patients (60 adults, 60 children) with confirmed chickenpox in Sarajevo between 2005 and 2011 reported that antiviral (acyclovir) therapy was initiated in 8 (13.5%) adults and 16 (27%) children. No deaths were recorded in that series.
Two studies examined immune predictors of severe chickenpox. A 2020 study found that in patients with positive viral DNA, levels of IFN-α and IFN-γ were significantly lower compared to patients with negative DNA results. Complications such as secondary viral-bacterial pneumonia could be predicted by low (less than double-normal) levels of IL-6 and IFN-γ, induced chemiluminescence, CD16, and CD20. A 2017 prospective study of 69 immunocompetent patients found that CD4+ percentage was significantly lower in hospitalised patients (moderate, severe or life-threatening forms) compared to outpatients (mild forms) and healthy controls. CD8+ percentage was higher and CD4/CD8 ratio lower in hospitalised patients.
What remains missing is a clear molecular explanation for the vaccine's attenuation beyond the gB variant, and any proven immune-correcting therapy for patients identified as at risk by the proposed immunological criteria. No randomised trial has tested whether stratifying patients by these immune markers and intervening alters outcomes. The 1994 case shows that even continuous acyclovir can fail in immunocompromised patients, but no new antiviral strategies have been tested in that population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
mBio · 2022 · 13 citations · open access
A Variant Allele in Varicella-Zoster Virus Glycoprotein B Selected during Production of the Varicella Vaccine Contributes to Its Attenuation
AbstractThe live-attenuated varicella vaccine has reduced the burden of chickenpox. Despite its development in 1974, the molecular basis for its attenuation is still not well understood. Since the live-attenuated varicella vaccine is the only licensed human herpesvirus vaccine that prevents primary disease, it is important to understand the mechanism for its attenuation. Here we identify that a variant allele in glycoprotein B (gB) selected during generation of the varicella vaccine contributes to its attenuation. This variant is impaired for fusion, virus entry into neurons from nerve terminals, and replication in human skin cells. Identification of a variant allele in gB, one of the essential herpesvirus core genes, that contributes to its attenuation may provide insights that assist in the development of other herpesvirus vaccines.
Relapsing Chickenpox in a Young Man with Non-Hodgkin's Lymphoma
AbstractReinfection of previously "immune" patients with varicella-zoster virus can result in recurrent chickenpox. However, relapses of chickenpox are not well recognized. We describe a young man with lymphoma who rapidly developed multiple, discrete relapses of chickenpox each time therapy with acyclovir was stopped. His cutaneous infection eventually became unremitting, despite continuous treatment with acyclovir. No evidence ever suggested visceral dissemination of varicella. The patient died suddenly; the cause of death was not determined.
Therapeutic Approach to Chickenpox in Children and Adults - our Experience
AbstractINTRODUCTION: Chickenpox is highly contagious childhood disease which occurs as a result of varicella-zoster virus primary infection. Symptomatic therapy is usually adequate for chickenpox, but in some cases it requires combinations of antiviral drugs and antibiotics. OBJECTIVES: To present our expirience with chickenpox therapy in children and adult patients. MATERIAL AND METHODS: Study included 120 randomly chosen patients, 60 adults and 60 children, with confirmed chickenpox infection, hospitalised at Clinic for infectious diseases in Sarajevo. Observed period was 1st January 2005. to 30th June 2011. We compared used therapy and outcome of disease. RESULTS: We had 333 patients with confirmed chickenpox in mentioned period. Male sex prevailed. Antiviral (acyclovir) therapy was initiated in 8(13.5%) adults and 16(27%) children. Most frequently used antibiotic was Co-Amoxiclav in a group of adults and Ceftriaxone in a group of children. DISCUSSION AND CONCLUSION: We use different terapeutical approaches to chickenpox according to the severity of the clinical picture and the existence of underlying diseases. Symptomatic treatment is indicated in all immunocompetent patients with no signs of complications. Use of corticosteroids remains open dillemma. Our therapeutical approcach followed by actual guidelines proved to be usefull. No death cases were recorded in these
Современные технологии в медицине · 2020 · 6 citations · open access
Immunological Criteria for Predicting Severe and Complicated Forms of Chickenpox
Abstractwas to evaluate the levels of mediators of the immune response, cellular immunity, and phagocytic activity in patients with chickenpox with various values of the clinical and laboratory parameters and propose criteria for predicting the severity and complications of the disease. MATERIALS AND METHODS: The blood levels of pro-inflammatory mediators were evaluated by ELISA using monoclonal antibodies (Protein Contour, Russia). RESULTS: DNA. We found that in patients with positive viral DNA, the levels of IFN-α and IFN-γ were significantly lower compared to patients with negative DNA results. Thus, complications of chickenpox, in particular secondary viral-bacterial pneumonia, can be predicted based on low (less than double-normal) levels of IL-6 and IFN-γ, induced chemiluminescence, CD16, and CD20. This type of immune response indicates the state of immune deficiency with prevailing suppression of the T-effector and phagocytic mechanisms in these patients. CONCLUSION: Prognosis of the development of severe and complicated forms of chickenpox can be based on the insufficiently increased (less than two normal values) levels of IL-6 and IFN-γ, induced chemiluminescence, CD16, and CD20. These relatively low levels are indicative of reduced immune response to the infection, which may require additional immune correcting therapy.
T-lymphocyte Subsets as a Prognostic Factor in a Clinical Course of Chickenpox
AbstractOBJECTIVE: To investigate possible prognostic values of CD4+, CD8+ T-lymphocytes, CD4/CD8 ratio to clinical course of chickenpox in immunocompetent hosts. MATERIALS AND METHODS: We performed a prospective study which included 69 immunocompetent patients with chickenpox who were addmited to Clinic for infectious disease, Clinical Center University of Sarajevo, in a 18 month period. All patients were divided into two groups depending on clinical presentation on admission. Patients with mild clinical form were dedicated to "outpatient" group, and patients with moderate, severe or life-threatening clinical forms were dedicated to "hospitalized" group. Also 30 healthy volunteers are included in study as a control group. We analyzed values of CD4+, CD8+ percentage, CD4/CD8 ratio with comparison to clinical course of chickenpox. All specimens were taken in acute phase of illness. RESULTS: Values of CD4+ percentage were significantly declined in a group of hospitalized patients, compared to group of outpatients and control group. Values of CD8+ percentage were higher in a group of hospitalized patients, while CD4/CD8 values were lower in comparison to a group of outpatients and control group. CONCLUSION: We found significant correlation between these parameters and clinical course of chickenpox.
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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