RARE DISEASE
Marburg hemorrhagic fever
Marburg hemorrhagic fever
Marburg hemorrhagic fever
Synonyms: Green monkey disease, MHF, Marburg virus disease
Synonyms: Green monkey disease, MHF, Marburg virus disease
Synonyms: Green monkey disease, MHF, Marburg virus disease
Drug discovery
4
drugs
With orphan designations
Overview
Marburg hemorrhagic fever (MHF) is a severe viral illness caused by Orthomarburgvirus, characterized by sudden fever, hemorrhagic manifestations, multi-organ failure, and case fatality rates of 24–90% [1][14][17]. Transmission occurs via contact with infected body fluids, with fruit bats (Rousettus aegyptiacus) as the primary reservoir. Early symptoms mimic malaria or typhoid, progressing to "wet" phases (vomiting, diarrhea) and potential bleeding [6][14][18]. Diagnosis requires RT-PCR or antigen testing, with strict infection control protocols critical to prevent nosocomial spread [1][6][16].
Population
Primarily affects sub-Saharan African regions; high-risk groups include miners, healthcare workers, and those in contact with bats or infected primates [7][14][17].
Recent outbreaks (2024–2025) reported in Tanzania (9 cases; 89% fatality) and Rwanda (62 cases; 24% fatality), with healthcare workers disproportionately impacted [15][19].
Therapies
Supportive care: Fluid/electrolyte management, oxygenation, and hemorrhage control remain cornerstone interventions [6][14][16].
Experimental approaches: Galidesivir (viral RNA polymerase inhibitor), Favipiravir (RNA mutagenesis), and remdesivir-monoclonal antibody combinations show preclinical promise [3][8][12].
Categories: rare infectious diseases
Research Papers
416 drug discovery papers about Marburg hemorrhagic fever, with 5 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
416 drug discovery papers about Marburg hemorrhagic fever, with 5 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-09 | Narrative review on Marburg virus disease aetiopathogenesis and management
Abstract On November 14th, 2025, the Ethiopian Ministry of Health confirmed the country’s first Marburg virus outbreak, representing another in a series of recent outbreaks across Africa in only 3 years. Marburg virus disease (MVD) is a highly lethal zoonotic haemorrhagic fever caused by the Marburg virus. This review synthesises the current evidence on MVD, covering epidemiology, pathogenesis, diagnostics, and emerging countermeasures, such as investigational antivirals and vaccines. Despite the severity of the disease outcome, no licensed treatment or vaccine exists. Recent outbreaks, including Rwanda (2024), Tanzania and Ethiopia (2025), have accelerated evaluation of investigational therapeutics such as remdesivir and monoclonal antibody MBP091 under expanded access and early‑phase studies; no randomised human efficacy data are currently available for MVD, alongside novel platforms including mRNA and adenovirus-vectored vaccines. Advances in molecular virology have helped to elucidate mechanisms of immune evasion and viral persistence, informing strategies for targeted interventions. Diagnostic capacity and therapeutic deployment remain constrained in resource-limited settings. Strengthening global preparedness will require integrated surveillance, rapid clinical trial frameworks, and equitable access to vaccines and antivirals.
2026-07-17 | AI-Driven Discovery and BSL-4 Validation of Cross-Filovirus Ebola-Marburg Inhibitors and their Synergistic Combinations.
Filovirus outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV), pose severe global health threats characterized by high rates of fatal hemorrhagic fever. While species-specific vaccines and therapeutic monoclonal antibodies are approved for Zaire ebolavirus, broadly-active therapeutics remain unavailable, leaving populations vulnerable to MARV and other pathogenic Ebola species, such as Bundibugyo (BDBV) and Sudan (SUDV) ebolaviruses. Here we report a computationally guided, infectious virus validated screening platform for the rapid discovery of broad-spectrum filovirus antivirals. By leveraging quantitative structure- activity relationship (QSAR) models, we screened 142,382 compounds in silico to prioritize 125 high-potential candidates. Subsequent dose-response and viability profiling identified 23 compounds exhibiting potent, low-micromolar pan-filovirus activity and favorable cytotoxicity profiles. Molecular docking indicates these compounds target conserved structural and functional domains-primarily the VP35 and L proteins-which may disrupt essential viral replication and immune antagonism. Furthermore, systematic combinatorial screening revealed three highly synergistic compound pairs, notably NCGC00113249-01 and NCGC00118008-01, demonstrating robust cross-species efficacy. By targeting conserved vulnerabilities across the filovirus family, this integrated in silico and in vitro pipeline provides a scalable framework to rapidly nominate and optimize synergistic therapeutic regimens against both endemic and emerging viral threats including BDBV.
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-07-11 | Epidemiology and containment of the first Marburg virus disease outbreak in Ethiopia in 2025: A retrospective descriptive study.
In November 2025, Ethiopia confirmed its first Marburg Virus Disease (MVD) outbreak in Jinka, marking a significant geographical expansion of the virus with a 64% case fatality rate. This study characterizes the transmission dynamics of the 2025 MVD outbreak in Ethiopia and evaluates the impact of the national public health containment strategy on the epidemic trajectory. We conducted a retrospective descriptive analysis using surveillance and laboratory data from November 14 to December 30, 2025. Transmission intensity was quantified using basic (R0) and effective (Rt) reproduction numbers. We further evaluated the deployment of the investigational cAd3-Marburg vaccine and the feasibility of drone-assisted ultra-cold chain logistics under the national Evidence Generation during an Emergency (EGE) framework. The outbreak involved 14 confirmed cases and 9 fatalities (CFR: 64%). The initial R0 was 2.34, driven by nosocomial and religious clusters. Following the activation of the Incident Management System, diagnostic testing increased by over 1000%, and 2500 vaccine doses were deployed to high-risk groups. The use of drone logistics was observed to support the -80 °C cold chain for deliveries in remote areas. Rt fell below 1.0 within 14 days of formal intervention. The findings are consistent with the hypothesis that the combination of rapid diagnostic scaling decentralized incident management and technological integration were temporally associated with the truncation of MVD transmission chains. The integrated approach of decentralized management and rapid technological deployment offers a framework for viral hemorrhagic fever preparedness in similar resource-limited settings.
2026-07-10 | Integrative reverse vaccinology and computational modeling for the rational design of a broadly immunogenic multi-epitope vaccine against Marburg virus infection.
Marburg virus (MARV), a member of the Filoviridae family, causes severe hemorrhagic fever in humans with case fatality rates exceeding 90%, and currently, no approved vaccines or therapeutics are available. To address this urgent need, we employed comprehensive immunoinformatics and computational approaches to design a multi-epitope subunit vaccine (MESV) capable of eliciting robust immune responses. Highly antigenic, non-allergenic, and non-toxic cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes derived from MARV glycoprotein (GP) and nucleoprotein (NP) were selected and assembled using appropriate linkers and adjuvant sequences. The designed vaccine construct exhibited favorable physicochemical characteristics, structural stability, and strong immunogenic potential. Solubility analysis predicted a score of 0.835, while structural validation revealed an ERRAT score of 94.11%, with 89.4% of residues located in the most favored regions of the Ramachandran plot. The ProSA analysis yielded a Z-score of - 5.31, confirming the reliability of the modeled structure. Molecular docking studies demonstrated strong interactions between the vaccine construct and Toll-like receptor 7, while molecular dynamics simulations confirmed the stability of the docked complex. Codon optimization and in silico cloning indicated efficient expression potential in Escherichia coli, with a codon adaptation index (CAI) of 0.9805 and GC content of 55.39%. Furthermore, immune simulations predicted a robust and sustained immune response. These computational findings suggest that the designed MESV is a promising vaccine candidate for MARV and warrants further experimental validation through in vitro and in vivo studies.
2026-08-09 | Narrative review on Marburg virus disease aetiopathogenesis and management
Abstract On November 14th, 2025, the Ethiopian Ministry of Health confirmed the country’s first Marburg virus outbreak, representing another in a series of recent outbreaks across Africa in only 3 years. Marburg virus disease (MVD) is a highly lethal zoonotic haemorrhagic fever caused by the Marburg virus. This review synthesises the current evidence on MVD, covering epidemiology, pathogenesis, diagnostics, and emerging countermeasures, such as investigational antivirals and vaccines. Despite the severity of the disease outcome, no licensed treatment or vaccine exists. Recent outbreaks, including Rwanda (2024), Tanzania and Ethiopia (2025), have accelerated evaluation of investigational therapeutics such as remdesivir and monoclonal antibody MBP091 under expanded access and early‑phase studies; no randomised human efficacy data are currently available for MVD, alongside novel platforms including mRNA and adenovirus-vectored vaccines. Advances in molecular virology have helped to elucidate mechanisms of immune evasion and viral persistence, informing strategies for targeted interventions. Diagnostic capacity and therapeutic deployment remain constrained in resource-limited settings. Strengthening global preparedness will require integrated surveillance, rapid clinical trial frameworks, and equitable access to vaccines and antivirals.
2026-07-17 | AI-Driven Discovery and BSL-4 Validation of Cross-Filovirus Ebola-Marburg Inhibitors and their Synergistic Combinations.
Filovirus outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV), pose severe global health threats characterized by high rates of fatal hemorrhagic fever. While species-specific vaccines and therapeutic monoclonal antibodies are approved for Zaire ebolavirus, broadly-active therapeutics remain unavailable, leaving populations vulnerable to MARV and other pathogenic Ebola species, such as Bundibugyo (BDBV) and Sudan (SUDV) ebolaviruses. Here we report a computationally guided, infectious virus validated screening platform for the rapid discovery of broad-spectrum filovirus antivirals. By leveraging quantitative structure- activity relationship (QSAR) models, we screened 142,382 compounds in silico to prioritize 125 high-potential candidates. Subsequent dose-response and viability profiling identified 23 compounds exhibiting potent, low-micromolar pan-filovirus activity and favorable cytotoxicity profiles. Molecular docking indicates these compounds target conserved structural and functional domains-primarily the VP35 and L proteins-which may disrupt essential viral replication and immune antagonism. Furthermore, systematic combinatorial screening revealed three highly synergistic compound pairs, notably NCGC00113249-01 and NCGC00118008-01, demonstrating robust cross-species efficacy. By targeting conserved vulnerabilities across the filovirus family, this integrated in silico and in vitro pipeline provides a scalable framework to rapidly nominate and optimize synergistic therapeutic regimens against both endemic and emerging viral threats including BDBV.
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-07-11 | Epidemiology and containment of the first Marburg virus disease outbreak in Ethiopia in 2025: A retrospective descriptive study.
In November 2025, Ethiopia confirmed its first Marburg Virus Disease (MVD) outbreak in Jinka, marking a significant geographical expansion of the virus with a 64% case fatality rate. This study characterizes the transmission dynamics of the 2025 MVD outbreak in Ethiopia and evaluates the impact of the national public health containment strategy on the epidemic trajectory. We conducted a retrospective descriptive analysis using surveillance and laboratory data from November 14 to December 30, 2025. Transmission intensity was quantified using basic (R0) and effective (Rt) reproduction numbers. We further evaluated the deployment of the investigational cAd3-Marburg vaccine and the feasibility of drone-assisted ultra-cold chain logistics under the national Evidence Generation during an Emergency (EGE) framework. The outbreak involved 14 confirmed cases and 9 fatalities (CFR: 64%). The initial R0 was 2.34, driven by nosocomial and religious clusters. Following the activation of the Incident Management System, diagnostic testing increased by over 1000%, and 2500 vaccine doses were deployed to high-risk groups. The use of drone logistics was observed to support the -80 °C cold chain for deliveries in remote areas. Rt fell below 1.0 within 14 days of formal intervention. The findings are consistent with the hypothesis that the combination of rapid diagnostic scaling decentralized incident management and technological integration were temporally associated with the truncation of MVD transmission chains. The integrated approach of decentralized management and rapid technological deployment offers a framework for viral hemorrhagic fever preparedness in similar resource-limited settings.
2026-07-10 | Integrative reverse vaccinology and computational modeling for the rational design of a broadly immunogenic multi-epitope vaccine against Marburg virus infection.
Marburg virus (MARV), a member of the Filoviridae family, causes severe hemorrhagic fever in humans with case fatality rates exceeding 90%, and currently, no approved vaccines or therapeutics are available. To address this urgent need, we employed comprehensive immunoinformatics and computational approaches to design a multi-epitope subunit vaccine (MESV) capable of eliciting robust immune responses. Highly antigenic, non-allergenic, and non-toxic cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes derived from MARV glycoprotein (GP) and nucleoprotein (NP) were selected and assembled using appropriate linkers and adjuvant sequences. The designed vaccine construct exhibited favorable physicochemical characteristics, structural stability, and strong immunogenic potential. Solubility analysis predicted a score of 0.835, while structural validation revealed an ERRAT score of 94.11%, with 89.4% of residues located in the most favored regions of the Ramachandran plot. The ProSA analysis yielded a Z-score of - 5.31, confirming the reliability of the modeled structure. Molecular docking studies demonstrated strong interactions between the vaccine construct and Toll-like receptor 7, while molecular dynamics simulations confirmed the stability of the docked complex. Codon optimization and in silico cloning indicated efficient expression potential in Escherichia coli, with a codon adaptation index (CAI) of 0.9805 and GC content of 55.39%. Furthermore, immune simulations predicted a robust and sustained immune response. These computational findings suggest that the designed MESV is a promising vaccine candidate for MARV and warrants further experimental validation through in vitro and in vivo studies.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
4 orphan drug designations for Marburg hemorrhagic fever.
4 orphan drug designations for Marburg hemorrhagic fever.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
galidesivir | small molecules | FDA | 2026-06-16 | — | Island Pharmaceuticals |
Subunit protein vaccine of recombinantly expressed Marburg Marburgvirus glycoprotein (MARV GP, MarVax) | proteins | FDA | 2024-04-08 | — | Soligenix, Inc. |
An immunoglobulin subclass 1 (IgG1) human monoclonal antibody that targets the Marburg virus (MARV) glycoprotein | antibodies | FDA | 2022-11-22 | — | Mapp Biopharmaceutical, Inc. |
5ÿ¿ÿÿÿ¢ÿ¿ÿÿ¬"-GAATATTAACAIACTGACAAGTC-3ÿ¿ÿÿÿ¢ÿ¿ÿÿ¬" | small molecules | FDA | 2012-10-31 | — | Sarepta Therapeutics, Inc. |
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