RARE DISEASE
Lassa fever
Lassa fever
Lassa fever
Synonyms: LF, Lassa hemorrhagic fever
Synonyms: LF, Lassa hemorrhagic fever
Synonyms: LF, Lassa hemorrhagic fever
Drug discovery
1
drug
With orphan designation
Overview
Lassa fever is an acute viral hemorrhagic illness caused by the Lassa virus, endemic in West Africa. Transmission occurs through contact with rodent excreta or contaminated materials, with human-to-human spread in healthcare settings lacking infection controls. Symptoms progress from nonspecific flu-like symptoms to multi-organ failure in severe cases (15% CFR in hospitalized patients). Early diagnosis remains challenging due to symptom overlap with malaria and typhoid. Ribavirin (IV/oral) is used as off-label treatment despite incomplete efficacy data, and supportive care is critical for survival [1][3][13].
Categories: rare infectious diseases
Research Papers
709 drug discovery papers about Lassa fever, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
709 drug discovery papers about Lassa fever, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | Lassa fever and Argentine hemorrhagic fever treatment in guinea pigs using broad-spectrum cap-dependent endonuclease inhibitors.
The class Bunyaviricetes encompasses several highly pathogenic viruses that cause lethal hemorrhagic fevers. Due to their limited prevention and treatment options and high pathogenicity, these viruses require handling in biosafety level-4 facilities. Within the bunyaviruses, arenaviruses are particularly notable for their pathogenicity and ability to cause severe hemorrhagic disease in humans. The cap-dependent endonuclease (CEN) is a unique and crucial enzyme involved in the replication cycle of these viruses. As humans do not possess a similar enzyme, CEN represents an ideal target for antiviral drug development with reduced risk of side effects. Recently, we identified a promising CEN inhibitor (CENi) demonstrating potent inhibition of virus replication. In this manuscript, we demonstrate the successful therapeutic efficacy of CENis against Lassa fever and Argentine hemorrhagic fever virus infections in guinea pig models of lethal hemorrhagic fever. In addition, we identified several CENis with antiviral activity against other highly pathogenic arenaviruses. These findings further support the potential of CENis as therapeutic agents for arenavirus infections that cause severe and often lethal hemorrhagic fever. Collectively, our results suggest that CENis are promising candidates for pan-arenavirus therapy and may also have broader utility against other CEN-containing viruses for which no approved antiviral treatments currently exist.IMPORTANCEArenaviruses, such as Lassa virus and Junin virus, cause severe hemorrhagic fevers in humans and are associated with high mortality rates and limited treatment options. Because of their pathogenicity and potential for outbreaks, these viruses represent an important global health threat. The viral cap-dependent endonuclease (CEN) plays a critical role in arenavirus replication by enabling the cap-snatching process required for viral mRNA synthesis. Notably, mammalian cells lack a comparable enzyme, making CEN an attractive target for antiviral drug development. In this study, we demonstrate that inhibitors targeting the arenavirus CEN effectively suppress viral replication and provide therapeutic protection in animal models of lethal Lassa virus and Junin virus infections. We also identify compounds with antiviral activity against multiple highly pathogenic arenaviruses. These findings establish CEN inhibition as a promising strategy for the development of broad-spectrum antivirals against arenaviruses that cause life-threatening hemorrhagic fevers.
2026-07-25 | Computational Design of a Broad-Spectrum Multi-Epitope mRNA Vaccine Candidate for Mammarenaviruses.
Mammarenaviruses cause serious diseases such as Lassa fever and Argentine hemorrhagic fever that threaten global public health; however, vaccines and therapeutic options remain limited. Therefore, developing a broadly effective vaccine against mammarenaviruses is a priority. In this study, we systematically analyzed the main structural protein sequences of ten mammarenaviruses. We combined antigenic epitopes from the Immune Epitope Database (IEDB) and used inverse vaccination and immunoinformatics methods to screen for highly conserved B- and T-cell epitopes with strong immunogenicity. We then added tissue plasminogen activator (tPA), which is the most effective vaccine against these pathogens. To construct a broad-spectrum multi-epitope fusion mRNA vaccine candidate, we included a tPA signal peptide, PADRE adjuvant, and linkers. The mRNA sequences were algorithm-optimized. We assessed the structural stability and immunogenicity of the candidate vaccine using molecular docking, molecular dynamics (MD) simulation, and immunosimulation. The designed vaccine had good antigenicity and structural stability, forming stable complexes with a variety of intrinsic immunoreceptors and triggering a strong, sustained, and comprehensive immune response during immunosimulation. Our study findings posit the designed vaccine as a potential broad-spectrum multi-epitope vaccine candidate against mammarenaviruses. Further real-world studies are required to validate these results.
2026-06-27 | Evaluating vectors for the design of a spillover-disrupting Lassa virus transmissible vaccine.
Lassa fever is a viral zoonotic disease that sickens tens of thousands of people each year when it spills over from its rodent reservoir throughout West Africa. Despite the burden this persistent spillover places on public health, stopping it has proven to be an intractable challenge despite decades of investment and effort. A revolutionary solution is the development of a transmissible vaccine that can spread through the rodent population resulting in immune coverage sufficient to eliminate Lassa virus transmission. Here, we evaluate the feasibility of a transmissible vaccine constructed from native cytomegaloviruses (CMVs) previously isolated from the natural reservoir of Lassa virus, Mastomys natalensis. Using a combination of field sampling, large-scale CMV genome characterization, and mathematical models parameterized using Bayesian methods, we quantified transmission rates and interactions among viruses in northern Sierra Leone. The results demonstrate that two of the three previously isolated CMVs co-infect freely and have R0 values consistent with autonomous elimination of Lassa virus from its rodent reservoir. These results set the stage for the development of a CMV vectored transmissible vaccine that could stop the spillover of Lassa virus throughout West Africa.
2026-06-26 | Missed Opportunities for Timely Diagnosis and Effective Therapeutic Management of Prolonged Fever: A Case Study of Confirmed Lassa Fever in N'Zérékoré, Guinea, 2022.
Lassa fever is a potentially fatal viral hemorrhagic disease caused by a ribonucleic acid (RNA) virus of the Arenaviridae family, endemic in West Africa. It is highly virulent and contagious in several countries, with a nonspecific clinical presentation that poses a major public health challenge. An in-depth investigative survey was conducted in N'Zérékoré to identify the transmission chain of a confirmed case of Lassa fever. This study reports a confirmed case of Lassa fever diagnosed 13 days after the onset of persistent fever. The disease was suspected at the regional hospital of N'Zérékoré following the worsening of the initial clinical picture, characterized by the onset of hemorrhagic manifestations and failure of antibiotic therapy. Confirmation of Lassa virus infection by reverse transcriptase-polymerase chain reaction (RT-PCR) on a blood sample was obtained a day prior to the patient's death. The patient did not receive ribavirin treatment and remained on the same antibiotic regimen (ceftriaxone) from the onset of fever, combined with dexamethasone, omeprazole, and a unit of blood transfusion. The therapeutic pathway of this confirmed Lassa fever case in N'Zérékoré highlights the need for improved management of viral hemorrhagic fevers and consideration of differential diagnoses when broad-spectrum antibiotic therapy fails.
2026-06-13 | In silico prioritization and cheminformatics identify structurally diverse small-molecule inhibitors of Lassa virus glycoprotein-mediated membrane fusion.
Lassa virus (LASV) is a hemorrhagic fever arenavirus of significant public health concern, infecting millions of people per year in Africa. Here, we developed a computational strategy to identify specific inhibitors of LASV glycoprotein-mediated virus cell entry, leveraging a previous screen of 297,156 small molecules from the MLPCN library, with the results deposited in the PubChem database. Data mining methods were developed to efficiently select small molecules prioritized for both potency and specificity in inhibiting Lassa virus infection. Cheminformatics classification then identified diverse chemical scaffolds that had not been previously reported. Representatives were evaluated against authentic LASV infection, yielding potencies as low as 10 nM. Investigation of the target mechanism compared vesicular stomatitis virus bearing the GPs of LASV, the distantly related Junín virus, and unrelated Ebola virus. The results identified three distinct chemical scaffolds that demonstrated strong LASV selectivity, each acting at the membrane fusion stage of virus cell entry. Sensitivity was mapped to regions of GP2 known to coordinate pH-triggered conformational rearrangements needed for membrane fusion. Time-of-addition experiments demonstrated loss of activity coincident with endosomal escape, and cell-cell fusion assays confirmed direct inhibition of GP-mediated syncytia formation. Together, these findings characterize each scaffold as an effective LASV fusion inhibitor and highlight the effectiveness of our combined computational and experimental approaches in identifying mechanistically informative antiviral scaffolds.
2026-08-17 | Lassa fever and Argentine hemorrhagic fever treatment in guinea pigs using broad-spectrum cap-dependent endonuclease inhibitors.
The class Bunyaviricetes encompasses several highly pathogenic viruses that cause lethal hemorrhagic fevers. Due to their limited prevention and treatment options and high pathogenicity, these viruses require handling in biosafety level-4 facilities. Within the bunyaviruses, arenaviruses are particularly notable for their pathogenicity and ability to cause severe hemorrhagic disease in humans. The cap-dependent endonuclease (CEN) is a unique and crucial enzyme involved in the replication cycle of these viruses. As humans do not possess a similar enzyme, CEN represents an ideal target for antiviral drug development with reduced risk of side effects. Recently, we identified a promising CEN inhibitor (CENi) demonstrating potent inhibition of virus replication. In this manuscript, we demonstrate the successful therapeutic efficacy of CENis against Lassa fever and Argentine hemorrhagic fever virus infections in guinea pig models of lethal hemorrhagic fever. In addition, we identified several CENis with antiviral activity against other highly pathogenic arenaviruses. These findings further support the potential of CENis as therapeutic agents for arenavirus infections that cause severe and often lethal hemorrhagic fever. Collectively, our results suggest that CENis are promising candidates for pan-arenavirus therapy and may also have broader utility against other CEN-containing viruses for which no approved antiviral treatments currently exist.IMPORTANCEArenaviruses, such as Lassa virus and Junin virus, cause severe hemorrhagic fevers in humans and are associated with high mortality rates and limited treatment options. Because of their pathogenicity and potential for outbreaks, these viruses represent an important global health threat. The viral cap-dependent endonuclease (CEN) plays a critical role in arenavirus replication by enabling the cap-snatching process required for viral mRNA synthesis. Notably, mammalian cells lack a comparable enzyme, making CEN an attractive target for antiviral drug development. In this study, we demonstrate that inhibitors targeting the arenavirus CEN effectively suppress viral replication and provide therapeutic protection in animal models of lethal Lassa virus and Junin virus infections. We also identify compounds with antiviral activity against multiple highly pathogenic arenaviruses. These findings establish CEN inhibition as a promising strategy for the development of broad-spectrum antivirals against arenaviruses that cause life-threatening hemorrhagic fevers.
2026-07-25 | Computational Design of a Broad-Spectrum Multi-Epitope mRNA Vaccine Candidate for Mammarenaviruses.
Mammarenaviruses cause serious diseases such as Lassa fever and Argentine hemorrhagic fever that threaten global public health; however, vaccines and therapeutic options remain limited. Therefore, developing a broadly effective vaccine against mammarenaviruses is a priority. In this study, we systematically analyzed the main structural protein sequences of ten mammarenaviruses. We combined antigenic epitopes from the Immune Epitope Database (IEDB) and used inverse vaccination and immunoinformatics methods to screen for highly conserved B- and T-cell epitopes with strong immunogenicity. We then added tissue plasminogen activator (tPA), which is the most effective vaccine against these pathogens. To construct a broad-spectrum multi-epitope fusion mRNA vaccine candidate, we included a tPA signal peptide, PADRE adjuvant, and linkers. The mRNA sequences were algorithm-optimized. We assessed the structural stability and immunogenicity of the candidate vaccine using molecular docking, molecular dynamics (MD) simulation, and immunosimulation. The designed vaccine had good antigenicity and structural stability, forming stable complexes with a variety of intrinsic immunoreceptors and triggering a strong, sustained, and comprehensive immune response during immunosimulation. Our study findings posit the designed vaccine as a potential broad-spectrum multi-epitope vaccine candidate against mammarenaviruses. Further real-world studies are required to validate these results.
2026-06-27 | Evaluating vectors for the design of a spillover-disrupting Lassa virus transmissible vaccine.
Lassa fever is a viral zoonotic disease that sickens tens of thousands of people each year when it spills over from its rodent reservoir throughout West Africa. Despite the burden this persistent spillover places on public health, stopping it has proven to be an intractable challenge despite decades of investment and effort. A revolutionary solution is the development of a transmissible vaccine that can spread through the rodent population resulting in immune coverage sufficient to eliminate Lassa virus transmission. Here, we evaluate the feasibility of a transmissible vaccine constructed from native cytomegaloviruses (CMVs) previously isolated from the natural reservoir of Lassa virus, Mastomys natalensis. Using a combination of field sampling, large-scale CMV genome characterization, and mathematical models parameterized using Bayesian methods, we quantified transmission rates and interactions among viruses in northern Sierra Leone. The results demonstrate that two of the three previously isolated CMVs co-infect freely and have R0 values consistent with autonomous elimination of Lassa virus from its rodent reservoir. These results set the stage for the development of a CMV vectored transmissible vaccine that could stop the spillover of Lassa virus throughout West Africa.
2026-06-26 | Missed Opportunities for Timely Diagnosis and Effective Therapeutic Management of Prolonged Fever: A Case Study of Confirmed Lassa Fever in N'Zérékoré, Guinea, 2022.
Lassa fever is a potentially fatal viral hemorrhagic disease caused by a ribonucleic acid (RNA) virus of the Arenaviridae family, endemic in West Africa. It is highly virulent and contagious in several countries, with a nonspecific clinical presentation that poses a major public health challenge. An in-depth investigative survey was conducted in N'Zérékoré to identify the transmission chain of a confirmed case of Lassa fever. This study reports a confirmed case of Lassa fever diagnosed 13 days after the onset of persistent fever. The disease was suspected at the regional hospital of N'Zérékoré following the worsening of the initial clinical picture, characterized by the onset of hemorrhagic manifestations and failure of antibiotic therapy. Confirmation of Lassa virus infection by reverse transcriptase-polymerase chain reaction (RT-PCR) on a blood sample was obtained a day prior to the patient's death. The patient did not receive ribavirin treatment and remained on the same antibiotic regimen (ceftriaxone) from the onset of fever, combined with dexamethasone, omeprazole, and a unit of blood transfusion. The therapeutic pathway of this confirmed Lassa fever case in N'Zérékoré highlights the need for improved management of viral hemorrhagic fevers and consideration of differential diagnoses when broad-spectrum antibiotic therapy fails.
2026-06-13 | In silico prioritization and cheminformatics identify structurally diverse small-molecule inhibitors of Lassa virus glycoprotein-mediated membrane fusion.
Lassa virus (LASV) is a hemorrhagic fever arenavirus of significant public health concern, infecting millions of people per year in Africa. Here, we developed a computational strategy to identify specific inhibitors of LASV glycoprotein-mediated virus cell entry, leveraging a previous screen of 297,156 small molecules from the MLPCN library, with the results deposited in the PubChem database. Data mining methods were developed to efficiently select small molecules prioritized for both potency and specificity in inhibiting Lassa virus infection. Cheminformatics classification then identified diverse chemical scaffolds that had not been previously reported. Representatives were evaluated against authentic LASV infection, yielding potencies as low as 10 nM. Investigation of the target mechanism compared vesicular stomatitis virus bearing the GPs of LASV, the distantly related Junín virus, and unrelated Ebola virus. The results identified three distinct chemical scaffolds that demonstrated strong LASV selectivity, each acting at the membrane fusion stage of virus cell entry. Sensitivity was mapped to regions of GP2 known to coordinate pH-triggered conformational rearrangements needed for membrane fusion. Time-of-addition experiments demonstrated loss of activity coincident with endosomal escape, and cell-cell fusion assays confirmed direct inhibition of GP-mediated syncytia formation. Together, these findings characterize each scaffold as an effective LASV fusion inhibitor and highlight the effectiveness of our combined computational and experimental approaches in identifying mechanistically informative antiviral scaffolds.
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
1 orphan drug designation for Lassa fever.
1 orphan drug designation for Lassa fever.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Ribavirin | small molecules | EMA | 2018-03-21 | — | Pharmadev Healthcare Ltd |
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