DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for Zika virus infectious disease — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleZika virus infectious disease maps to a 4-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 zika virus 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
CD8 subunit alpha (CD8A) — CD8A 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 6-formyl-4-oxo-3,4-dihydropteridin-2-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7UMG · 2.4 Å · ligand N-(6-formyl-4-oxo-3,4-dihydropteridin-2-yl)acetamide (30W). Experimental structure, not a prediction.
What the evidence adds up to
Zika virus is an emergent flavivirus linked to microcephaly in neonates and Guillain-Barré syndrome in adults, but no vaccine or clinically approved drug exists. One study identified seventy-nine FDA-approved drugs — including antineoplastics, antivirals, antibiotics, statins, and nutraceuticals — by datamining host genome targets shared with related flaviviruses, but these candidates have not been verified in Zika-infected patients. Another group found that the compound PRO2000 protected human cells from Zika-induced damage in an impedance-based assay, though the sample size and quantitative protection data are not reported in the abstract.
Host cell metabolism offers a separate line of attack. A 2023 study established that Zika virus replication depends on NAD(H) metabolism and glycolysis, and that the Nrf2/GSH/NADP(H)-dependent antioxidant response antagonises infection. The authors propose NAD(H) antimetabolites as potential inhibitors, but no in vivo or clinical data are provided. A 2018 review notes that several ongoing clinical trials for Zika vaccines, led by government and private pharmaceutical companies, have shown promise, but it does not name any drug, report response rates, or give survival figures.
The evidence remains preclinical and fragmentary. The seventy-nine FDA-approved drugs are purely computational predictions; PRO2000 has been tested only in cell culture; the NAD(H) antimetabolite strategy has not moved beyond mechanistic description. No randomised controlled trial of any repurposed drug against Zika virus has been completed. What is missing is funding for phase 2/3 trials, a validated patient stratification strategy (especially for pregnant women and neonates), and a standardised clinical endpoint that captures both acute infection and neurological sequelae.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 2016 · 129 citations
Zika virus: An emergent neuropathological agent
AbstractThe emergence of Zika virus in the Americas has followed a pattern that is familiar from earlier epidemics of other viruses, where a new disease is introduced into a human population and then spreads rapidly with important public health consequences. In the case of Zika virus, an accumulating body of recent evidence implicates the virus in the etiology of serious pathologies of the human nervous system, that is, the occurrence of microcephaly in neonates and Guillain-Barré syndrome in adults. Zika virus is an arbovirus (arthropod-borne virus) and a member of the family Flaviviridae, genus Flavivirus. Zika virions are enveloped and icosahedral, and contain a nonsegmented, single-stranded, positive-sense RNA genome, which encodes 3 structural and 7 nonstructural proteins that are expressed as a single polyprotein that undergoes cleavage. Zika genomic RNA replicates in the cytoplasm of infected host cells. Zika virus was first detected in 1947 in the blood of a febrile monkey in Uganda's Zika Forest and in crushed suspensions of the Aedes mosquito, which is one of the vectors for Zika virus. The virus remained obscure, with a few human cases confined to Africa and Asia. There are two lineages of the Zika virus, African and Asian, with the Asian strain causing outbreaks in Micronesia in 2007 and French Polynesia in 2013-2014. From here, the virus spread to Brazil with the first report of autochthonous Zika transmission in the Americas in March 2015. The rapid advance of the virus in the Americas and its likely association with microcephaly and Guillain-Barré syndrome make Zika an urgent public health concern. Ann Neurol 2016;80:479-489.
JAMA Neurology · 2016 · 74 citations · open access
Zika Virus as an Emerging Global Pathogen
AbstractIMPORTANCE: Zika virus (ZIKV) is an emerging arthropod-borne virus (arbovirus) in the genus Flavivirus that has caused a widespread outbreak of febrile illness, is associated with neurological disease, and has spread across the Pacific to the Americas in a short period. OBSERVATIONS: In this review, we discuss what is currently known about ZIKV, neuroimmunologic complications, and the impact on global human health. Zika virus spread across Africa and Asia in part owing to unique genomic evolutionary conditions and pressures resulting in specific human disease manifestations, complications, and pathogenesis. Recent data suggest that acute ZIKV infection in pregnant women may result in acute infection of fetal tissue and brain tissue, causing microcephaly and potentially severe debilitation of the infant or even death of the fetus. Cases of acute ZIKV are also associated with Guillain-Barré syndrome. With the increased number of cases, new complications such as ocular involvement and sexual transmission have been reported. CONCLUSIONS AND RELEVANCE: Zika virus is an emerging viral pathogen with significant consequences on human health throughout the world. Ongoing research into this pathogen is urgently needed to produce viable vaccine and therapeutic options.
Journal of Virology · 2023 · 37 citations · open access
Redox Regulation and Metabolic Dependency of Zika Virus Replication: Inhibition by Nrf2-Antioxidant Response and NAD(H) Antimetabolites
AbstractZika virus (ZIKV) is a major public health concern of international proportions. While the incidence of ZIKV infections has declined substantially in recent years, the potential for the reemergence or reintroduction remains high. Although viral infection alters host cell metabolism and homeostasis to promote its replication, deciphering the mechanism(s) involved in these processes is important for identifying therapeutic targets. The present work reveals the complexities of host cell redox regulation and metabolic dependency of ZIKV replication. An antagonistic effect of the Nrf2/GSH/NADP(H)-dependent antioxidant response against ZIKV infection and an essential role of NAD(H) metabolism and glycolysis for viral replication are established for the first time. These findings highlight the potential use of NAD(H) antimetabolites to counter ZIKV infection and pathogenesis.
Monoclonal Antibodies against Zika Virus NS1 Protein Confer Protection via Fc<b>γ</b>Receptor-Dependent and -Independent Pathways
AbstractZika virus (ZIKV) is a mosquito-borne flavivirus that has been linked to congenital microcephaly during recent epidemics. No licensed antiviral drug or vaccine is available. Monoclonal antibodies (MAbs) against the nonstructural protein 1 (NS1) inhibit ZIKV pathogenicity but do not enhance the disease as envelope protein-targeted MAbs do. However, the protection mechanisms are not fully understood. Here, we show that in the presence or absence of Fcγ receptor-bearing effector cells, NS1-targeted human MAbs 3G2 and 4B8 inhibit ZIKV infection. Compared to MAb 4F10 that has no inhibitory effects without effector cells, 3G2 and 4B8 confer better protection in ZIKV-infected neonatal mice. Destroying the Fc-mediated effector function reduces but does not abolish the protection of 3G2 and 4B8, suggesting that they engage both Fcγ receptor-dependent and -independent pathways. The protective efficacy of NS1-targeted MAbs may be associated with their epitope recognition. Our findings will help to develop NS1-based vaccines and therapeutics.
Annals of Clinical Microbiology and Antimicrobials · 2016 · 26 citations · open access
Management of infection by the Zika virus
AbstractA panel of national experts was convened by the Brazilian Infectious Diseases Society in order to organize the national recommendations for the management of zika virus infection. The focus of this document is the diagnosis, both clinical and laboratorial, and appropriate treatment of the diverse manifestations of this infection, ranging from acute mild disease to Guillain-Barré syndrome and also microcephaly and congenital malformations.
Microbiology Spectrum · 2022 · 12 citations · open access
In-Depth Characterization of Zika Virus Inhibitors Using Cell-Based Electrical Impedance
AbstractZika virus can cause serious disease in humans. Unfortunately, no antiviral drugs are available to treat infection. Here, we use an impedance-based method to continuously monitor virus infection in-and damage to-human cells. We can determine the Zika viral dose with this technique and also evaluate whether antiviral compounds protect the cells from damage caused by virus replication. We also show that this technique can be used to further unravel the characteristics of these compounds, such as their toxicity to the cells, and that it might even give further insight in their mechanism of antiviral action. Finally, we also find a novel Zika virus inhibitor, PRO2000. Overall, in this study, we use the impedance technology to-for the first time-evaluate compounds with anti-Zika virus properties, and therefore it can add valuable information in the further search for antiviral drugs.
Zika virus Therapeutics: Drug Targets and Repurposing Medicine from the Human Genome
AbstractZika viral infection is caused by an emerging mosquito borne virus the Zika virus ZIKV and threatens to become a global pandemic While not life threatening the Zika Virus Disease ZVD is suspected to be associated with severe neurological disorders including Guillain Barr eacute syndrome and microcephaly Currently no known cure or diagnostic tests for ZVD are available The host cell molecular targets are unknown for ZIKV The ZIKV is related to various other mosquito borne viruses including the Chikungunya Dengue Japanese encephalitis Spondweni Yellow fever and West Nile viruses The host cell targets are known for most of these viruses All of these viruses harbor common protein motifs and domains raising the possibility of shared molecular targets in the host genome To facilitate target s discovery for the ZIKV therapy the disease and protein knowledge databases were datamined for Zika related viruses An initial database of genes was established Additional filtering using variants associated with the Zika related viruses and neurological disease phenotypes identified putative candidate ZIKV targets These encompass druggable proteins including adhesion molecules chemokines enzymes interleukins receptors and transporters Genes linked to Guillain Barr eacute syndrome and microcephaly was among the Zika candidate genes The protein expression of the candidate genes was detected in diverse body fluids Drug bank datamining of these candidate targets identified seventy nine FDA approved drugs of the class antineoplastics anti diabetic anti inflammatory antivirals antibiotics statins and neutraceuticals The database of genes from the study provides a framework for diagnosis and therapy of the ZVD The FDA approved list of drugs if verified may offer a repurposing use for the treatment of the ZVD
Journal of Pharmaceutics & Drug Delivery Research · 2018 · 1 citations
Recent Developments on Conquering Zika
AbstractRecently, the World Health Organization (WHO) has declared that Zika, a virus, which has been linked to birth defects and neurological complications, no longer constitutes an international emergency. However, it still remains a threat which calls for a long term efforts to address the issue through development of vaccines. Several ongoing clinical trials led by government and private pharmaceutical companies have shown a great promise in the treatment of Zika. Apart from these trials, there are also ongoing research on understanding the virus better, its transmission mode and future possibility of leveraging it in other disease treatments. This article provides an insight on these efforts and their findings.
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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