Lassa Virus Research Articles

Discovering Lassa virus nucleoprotein inhibitors via in silico drug repositioning approach

Discovering Lassa virus nucleoprotein inhibitors via in silico drug repositioning approach

Preliminary evidence that Bunyamwera virus causes severe disease characterized by systemic vascular and multiorgan necrosis in an immunocompromised mouse model.

Bunyamwera virus (BUNV) is the prototypical member of the Bunyamwera serogroup within the Orthobunyvirus genus. BUNV is transmitted by mosquito vectors of the genera Culex, Aedes and Anopheles and has historically circulated in East Africa, though the transmission has been observed in Argentina. BUNV has been identified as an agent of human and animal disease and has also been misdiagnosed as other agents. BUNV is often thought to be an agent of mild febrile illness in humans, though it can cause abortions in ruminants and neurological disease in horses. Joint pain and gastritis have also been attributed to BUNV. There are limited data concerning the possible spectrum of disease and extent of pathogenesis of BUNV infection, and there are currently no therapeutics or vaccines available. Furthermore, options for animal models for Orthobunyaviruses in general - of which BUNV is the prototypical member - are limited. Eight mice deficient in the type I interferon response were infected with BUNV, and all developed overt disease. All mice developed detectable viraemia and clinical signs, including weight loss, hunched posture and lethargy. Three of the eight mice developed severe diseases, including vascular necrosis and necrosis in the liver, lungs, reproductive organs, bone marrow and spleen, as well as haemorrhages (n=1) and severe diffuse facial oedema (n=3), reminiscent of the pathology of Schmallenberg and the Arenaviruses Lassa and Lujo viruses. Thus, BUNV infection of IRF3/7 DKO mice could serve as a BSL-2 model for severe diseases of higher-risk group viruses, which often must be studied at BSL-4. Additionally, our results suggest that BUNV may have the ability to cause severe disease in immunocompromised hosts. Thus, further investigation into the potential spectrum of pathogenesis due to BUNV is important to prioritize for outbreak response, diagnostics and the development of countermeasures.

Lassa virus persistence with high viral titers following experimental infection in its natural reservoir host, Mastomys natalensis

Lassa virus (LASV) outbreaks in West Africa pose a significant public health threat. We investigated the infection phenotype and transmission (horizontal and vertical) of LASV strain Ba366 in its natural host, Mastomys natalensis. Here we analyze viral RNA levels in body fluids, virus titers in organs and antibody presence in blood. In adults and 2-week-old animals, LASV causes transient infections with subsequent seroconversion. However, mice younger than two weeks exhibit persistent infections lasting up to 16 months despite antibody presence. LASV can be detected in various body fluids, organs, and cell types, primarily in lung, kidney, and gonadal epithelial cells. Despite the systemic virus presence, no pathological alterations in organs are observed. Infected animals efficiently transmit the virus throughout their lives. Our findings underscore the crucial role of persistently infected individuals, particularly infected females and their progeny, in LASV dissemination within the host population.

Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.

Characterization of bi-segmented and tri-segmented recombinant Pichinde virus particles.

Mammarenaviruses include several highly virulent pathogens (e.g., Lassa virus) capable of causing severe hemorrhagic fever diseases for which there are no approved vaccines and limited treatment options. Mammarenaviruses are enveloped, bi-segmented ambisense RNA viruses. There is limited knowledge about cellular proteins incorporated into progeny virion particles and their potential biological roles in viral infection. Pichinde virus (PICV) is a prototypic arenavirus used to characterize mammarenavirus replication and pathogenesis. We have developed a recombinant PICV with a tri-segmented RNA genome as a viral vector platform. Whether the tri-segmented virion differs from the wild-type bi-segmented one in viral particle morphology and protein composition has not been addressed. In this study, recombinant PICV (rPICV) virions with a bi-segmented (rP18bi) and a tri-segmented (rP18tri) genome were purified by density-gradient ultracentrifugation and analyzed by cryo-electron microscopy and mass spectrometry. Both virion types are pleomorphic with spherical morphology and have no significant difference in size despite rP18tri having denser particles. Both virion types also contain similar sets of cellular proteins. Among the highly enriched virion-associated cellular proteins are components of the endosomal sorting complex required for transport pathway and vesicle trafficking, such as ALIX, Tsg101, VPS, CHMP, and Ras-associated binding proteins, which have known functions in virus assembly and budding. Other enriched cellular proteins include peripheral and transmembrane proteins, chaperone proteins, and ribosomal proteins; their biological roles in viral infection warrant further analysis. Our study provides important insights into mammarenavirus particle formation and aids in the future development of viral vectors and antiviral discovery.IMPORTANCEMammarenaviruses, such as Lassa virus, are enveloped RNA viruses that can cause severe hemorrhagic fever diseases (Lassa fever) with no approved vaccine and limited therapeutic options. Cellular proteins incorporated into progeny virion particles and their biological roles in mammarenavirus infection have not been well characterized. Pichinde virus (PICV) is a prototypic mammarenavirus used as a surrogate model for Lassa fever. We used cryo-electron microscopy and proteomic analysis to characterize the morphology and protein contents of the purified PICV particles that package either two (bi-segmented) or three (tri-segmented) genomic RNA segments. Our results demonstrate a similar virion morphology but different particle density for the bi- and tri-segmented viral particles and reveal major virion-associated cellular proteins. This study provides important insights into the virus-host interactions that can be used for antiviral development and optimizing arenavirus-based vaccine vectors.

"Pathological Insights into Lassa Virus-Induced Vestibular Dysfunction in Mice: Histopathological Analysis of the Inner Ear Vestibular Apparatus".

Lassa fever (LF), caused by Lassa virus (LASV) infection, typically leads to mild symptoms in humans, yet some survivors experience audiovestibular problems. Here we present vestibular histopathological insights in our LF model mice. We observed: 1) hemorrhage within the vestibular ganglion and stroma beneath the sensory epithelium, 2) preserved hair cells and supporting cells, 3) LASV antigen presence in the vestibular ganglion cells and the stroma beneath the sensory epithelium, and 4) CD3-positive T lymphocyte infiltration in the vestibular ganglion and the stroma underlying the sensory epithelium. LASV and/or its immune response likely contributes to the pathogenesis of vestibular dysfunction.

A validated and standardized pseudotyped microneutralization assay as a safe and powerful tool to measure LASSA virus neutralising antibodies for vaccine development and comparison.

Over the past few decades, World Health Organization (WHO) has made massive efforts to promote the development of a vaccine against Lassa virus (LASV), one of the top ten priority pathogens for research and development under the WHO R&D Blueprint for Emerging Infections. To date, several vaccines are at different stages of development. In this scenario, a validated and standardised assay to measure LASV neutralising antibodies is urgently needed for vaccine development and comparison. The neutralisation assay remains the gold standard for determining antibody efficacy. Here we have proposed a safe and validated pseudotyped neutralisation assay for LASV, taking advantage of the development of the first WHO International Standard and Reference Panel for Anti-Lassa Fever (NIBSC code 21/332). The proposed results demonstrate that the pseudotyped luciferase neutralisation assay is a specific serological test for the measurement of LASV neutralising antibodies without cross-reacting with standard sera specific for heterologous viral infections. In addition, the assay is accurate, precise, and linear according to criteria and statistical analyses defined and accepted by international guidelines.

Seroprevalence and risk factors for Lassa virus infection in South-West and North-Central Nigeria: a community-based cross-sectional study.

Understanding the level of exposure to Lassa virus (LASV) in at-risk communities allows for the administration of effective preventive interventions to mitigate epidemics of Lassa fever. We assessed the seroprevalence of LASV antibodies in rural and semiurban communities of two cosmopolitan cities in Nigeria with poorly understood Lassa epidemiology. A cross-sectional study was conducted in ten communities located in the Abuja Municipal Area Council (AMAC), Abuja, and Ikorodu Local Government Area (LGA), Lagos, from February 2nd to July 5th, 2022. Serum samples collected from participants were analyzed for IgG and IgM antibodies using a ReLASV® Pan-Lassa NP IgG/IgM enzyme-linked immunosorbent assay (ELISA) kit. A questionnaire administered to participants collected self-reported sociodemographic and LASV exposure information. Seroprevalence of LASV IgG/IgM was estimated overall, and by study site. Univariate and multivariate log-binomial models estimated unadjusted and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CI) for site-specific risk factors for LASV seropositivity. Grouped Least Absolute Shrinkage and Selection Operator (LASSO) was used for variable selection for multivariate analysis. A total of 628 participants with serum samples were included in the study. Most participants were female (434, 69%), married (459, 73%), and had a median age of 38 years (interquartile range 28-50). The overall seroprevalence was 27% (171/628), with a prevalence of 33% (126/376) in Abuja and 18% (45/252) in Lagos. Based on site-specific grouped LASSO selection, enrollment in the dry season (vs. wet; aPR, 95% CI: 1.73, 1.33-2.24), reported inconsistent washing of fruits and vegetables (aPR, 95% CI: 1.45, 1.10-1.92), and a positive malaria rapid test (aPR, 95% CI: 1.48, 1.09-2.00) were independently associated with LASV seropositivity in Abuja, whereas, only a self-reported history of rhinorrhea (PR, 95% CI: 2.21, 1.31-3.72) was independently associated with Lassa seropositivity in Lagos. The LASV seroprevalence was comparable to that in other areas in Nigeria. Our findings corroborate those from other studies on the importance of limiting human exposure to rodents and focusing on behavioral factors such as poor hygiene practices to reduce exposure to LASV.

Electroencephalography in emerging viral infections: Lessons learned from implementing an EEG unit in a Lassa fever isolation ward in Nigeria.

Electroencephalography (EEG) has been used for almost a century in well-equipped medical centers to facilitate the diagnosis of epilepsy and other brain disorders. Lassa fever (LF) and other emerging viral infections (EVI) are known to cause neurological complications, including meningitis, seizures, and encephalopathy, though to date it remains unclear whether these are secondary to metabolic disturbances caused by the disease or by direct involvement of the central nervous system (CNS). To better characterize how Lassa virus (LASV) affects the CNS, we established an EEG diagnostic unit in the LF isolation ward at Irrua Specialist Teaching Hospital in Edo State, Nigeria. Here, we report on the specific difficulties to successful implementation of EEG in this highly challenging setting. Technical artefacts due to electrical interferences and interrupted power supply, artefacts deriving from a partly improvised EEG setup within a high consequence pathogen isolation ward, and environmental factors, such as heat in the endemic West African setting are among the main difficulties encountered when setting up this diagnostic facility. It takes experienced neurophysiologists to distinguish such artefacts from actual EEG abnormalities as many of them are not commonly encountered to this extent in well-equipped EEG laboratories and can easily be confused with pathologies. The EEG recording process is further complicated by biosafety considerations and the necessity of wearing extensive personal protective equipment. Nevertheless, with the help of experienced neurophysiologists, it is possible to correctly set up the facility and interpret recordings. Taking the above into consideration, EEG is valuable in identifying CNS involvement in emerging infections, particularly regarding assessment of encephalitis, differential diagnosis of impaired consciousness and treatment adjustment in patients with symptomatic seizures. Although highly challenging under these circumstances, EEG can be an important, noninvasive diagnostic tool for neurological complications in EVI where other more advanced imaging modalities are not available.

Virus Load Kinetics in Lassa Fever Patients Treated With Ribavirin: A Retrospective Cohort Study From Southern Nigeria

Abstract Background The standard of care for Lassa fever is the use of ribavirin with supportive therapy. There is little information on the course of viremia and its relationship with clinical outcomes in patients treated with ribavirin. Methods We conducted a retrospective analysis of virologic and clinical parameters of 152 reverse transcription polymerase chain reaction–confirmed Lassa fever cases admitted and treated with ribavirin therapy. We describe the Lassa virus RNA kinetics in blood in relation to the clinical course of the patients. Results The overall mortality was 9%. The median duration (interquartile range [IQR]) of illness before admission was 8 (5–12) days. Median (IQR) Ct values on admission (t0) were lower among patients who died (21 [20–27]) than in those who survived (34 [30–37]; P < .01). The receiver operating characteristics curve of the association between outcome and Ct value at t0 had a high classification performance, with an AUC of 0.92 (95% CI, 0.86–0.98). The median time to viral clearance (IQR) was 10 (5–15) days. The viral load decreased steadily with the duration of treatment, and all survivors achieved viral clearance within 25 days of hospitalization. Conclusions Our study demonstrates that the Ct value on admission has prognostic value and Lassa fever patients treated with ribavirin typically clear the virus within 3–4 weeks of hospitalization. This kinetics has implications for the design of clinical case management and future clinical trial protocols.

Applied One Health: Nigeria National Veterinary Research Institute COVID-19 pandemic response.

The COVID-19 pandemic has caused the death of 7.1 million people worldwide as of 7 July 2024. In Nigeria, the first confirmed case was reported on 27 February 2020, subsequently followed by a nationwide spread of SARS-CoV-2 with morbidity and mortality reaching 267 173 and 3155, respectively, as of 7 July 2024. At the beginning of the pandemic, only a few public health laboratories in Nigeria had the capacity for SARS-CoV-2 molecular diagnosis. The National Veterinary Research Institute (NVRI), already experienced in influenza diagnosis, responded to the public health challenge for the diagnosis of COVID-19 samples from humans. The feat was possible through the collective utilisation of NVRI human and material resources, including biosafety facilities, equipment, reagents and consumables donated by international partners and collaborators. Within 6 months of the reported COVID-19 outbreak in Nigeria, over 33 000 samples were processed in NVRI facilities covering five states. Thereafter, many field and laboratory projects were jointly implemented between NVRI and collaborating sectors including the Nigerian Centre for Disease Control (NCDC) and the National Institute for Medical Research (NIMR), which brought together professionals in the health, veterinary, education and socio-sciences. In addition, One Health grants were secured to enhance surveillance for coronavirus and other zoonoses and build capacity in genomics. Bio-surveillance for coronaviruses and other emerging zoonotic pathogens at the human-animal interface was activated and continued with sample collection and analysis in the laboratory for coronaviruses, Lassa fever virus and Mpox. One Health approach has shown that inter-sectoral and multinational collaboration for diagnosis, research and development in animals, and the environment to better understand pathogen spillover events at the human-animal interface is an important global health priority and pandemic preparedness.

Health and economic impacts of Lassa vaccination campaigns in West Africa.

Lassa fever is a zoonotic disease identified by the World Health Organization (WHO) as having pandemic potential. This study estimates the health-economic burden of Lassa fever throughout West Africa and projects impacts of a series of vaccination campaigns. We also model the emergence of 'Lassa-X'-a hypothetical pandemic Lassa virus variant-and project impacts of achieving 100 Days Mission vaccination targets. Our model predicted 2.7 million (95% uncertainty interval: 2.1-3.4 million) Lassa virus infections annually, resulting over 10 years in 2.0 million (793,800-3.9 million) disability-adjusted life years (DALYs). The most effective vaccination strategy was a population-wide preventive campaign primarily targeting WHO-classified 'endemic' districts. Under conservative vaccine efficacy assumptions, this campaign averted $20.1 million ($8.2-$39.0 million) in lost DALY value and $128.2 million ($67.2-$231.9 million) in societal costs (2021 international dollars ($)). Reactive vaccination in response to local outbreaks averted just one-tenth the health-economic burden of preventive campaigns. In the event of Lassa-X emerging, spreading throughout West Africa and causing approximately 1.2 million DALYs within 2 years, 100 Days Mission vaccination averted 22% of DALYs given a vaccine 70% effective against disease and 74% of DALYs given a vaccine 70% effective against both infection and disease. These findings suggest how vaccination could alleviate Lassa fever's burden and assist in pandemic preparedness.

Inactivation Validation of Ebola, Marburg, and Lassa Viruses in AVL and Ethanol-Treated Viral Cultures.

High-consequence pathogens such as the Ebola, Marburg, and Lassa viruses are handled in maximum-containment biosafety level 4 (BSL-4) laboratories. Genetic material is often isolated from such viruses and subsequently removed from BSL-4 laboratories for a multitude of downstream analyses using readily accessible technologies and equipment available at lower-biosafety level laboratories. However, it is essential to ensure that these materials are free of viable viruses before removal from BSL-4 laboratories to guarantee sample safety. This study details the in-house procedure used for validating the inactivation of Ebola, Marburg, and Lassa virus cultures after incubation with AVL lysis buffer (Qiagen) and ethanol. This study's findings show that no viable virus was detectable when high-titer cultures of Ebola, Marburg, and Lassa viruses were incubated with AVL lysis buffer for 10 min, followed by an equal volume of 95% ethanol for 3 min, using a method with a sensitivity of ≤0.8 log10 TCID50 as the limit of detection.

The structure of the Lujo virus spike complex

Lujo virus (LUJV) is a human pathogen that was the cause of a deadly hemorrhagic fever outbreak in Africa. LUJV is a divergent member of the Arenaviridae with some similarities to both the “Old World” and “New World” serogroups, but it uses a cell-entry receptor, neuropilin-2 (NRP2), that is distinct from the receptors of OW and NW viruses. Though the receptor binding domain of LUJV has been characterized structurally, the overall organization of the trimeric spike complex and how NRP2 is recognized in this context were unknown. Here, we present the structure of the membrane-embedded LUJV spike complex determined by cryo-electron microscopy. Analysis of the structure suggested that a single NRP2 molecule is bound at the apex of the trimeric spike and that multiple subunits of the trimer contact the receptor. The binding of NRP2 involves an intriguing arginine-methionine interaction, which we analyzed using quantum mechanical modeling methods. We compare the LUJV spike structure with the only other available structure of a complete arenaviral spike, which is the Lassa virus. The similarities and differences between them shed light on Arenavirus evolution, inform vaccine design, and provide information that will be useful in combating future Arenavirus outbreaks.

Simultaneous screening for selective SARS-CoV-2, Lassa, and Machupo virus entry inhibitors

Emerging highly pathogenic viruses can pose profound impacts on global health, the economy, and society. To meet that challenge, the National Institute of Allergy and Infectious Diseases (NIAID) established nine Antiviral Drug Discovery (AViDD) centers for early-stage identification and validation of novel antiviral drug candidates against viruses with pandemic potential. As part of this initiative, we established paired entry assays that simultaneously screen for inhibitors specifically targeting SARS-CoV-2 (SARS2), Lassa virus (LASV) and Machupo virus (MACV) entry. To do so we employed a dual pseudotyped virus (PV) infection system allowing us to screen ∼650,000 compounds efficiently and cost-effectively. Adaptation of these paired assays into 1536 well-plate format for ultra-high throughput screening (uHTS) resulted in the largest screening ever conducted in our facility, with over 2.4 million wells completed. The paired infection system allowed us to detect two PV infections simultaneously: LASV + MACV, MACV + SARS2, and SARS2 + LASV. Each PV contains a different luciferase reporter gene which enabled us to measure the infection of each PV exclusively, albeit in the same well. Each PV was screened at least twice utilizing different reporters, which allowed us to select the inhibitors specific to a particular PV and to exclude those that hit off targets, including cellular components or the reporter proteins. All assays were robust with an average Z’ value ranging from 0.5 to 0.8. The primary screening of ∼650,000 compounds resulted in 1812, 1506, and 2586 unique hits for LASV, MACV, and SARS2, respectively. The confirmation screening narrowed this list further to 60, 40, and 90 compounds that are unique to LASV, MACV, and SARS2, respectively. Of these compounds, 8, 35, and 50 compounds showed IC50 value < 10 μM, some of which have much greater potency and excellent antiviral activity profiles specific to LASV, MACV, and SARS2, and none are cytotoxic. These selected compounds are currently being studied for their mechanism of action and to improve their specificity and potency through chemical modification.

Quantifying the risk of spillover reduction programs for human health.

Reducing spillover of zoonotic pathogens is an appealing approach to preventing human disease and minimizing the risk of future epidemics and pandemics. Although the immediate human health benefit of reducing spillover is clear, over time, spillover reduction could lead to counterintuitive negative consequences for human health. Here, we use mathematical models and computer simulations to explore the conditions under which unanticipated consequences of spillover reduction can occur in systems where the severity of disease increases with age at infection. Our results demonstrate that, because the average age at infection increases as spillover is reduced, programs that reduce spillover can actually increase population-level disease burden if the clinical severity of infection increases sufficiently rapidly with age. If, however, immunity wanes over time and reinfection is possible, our results reveal that negative health impacts of spillover reduction become substantially less likely. When our model is parameterized using published data on Lassa virus in West Africa, it predicts that negative health outcomes are possible, but likely to be restricted to a small subset of populations where spillover is unusually intense. Together, our results suggest that adverse consequences of spillover reduction programs are unlikely but that the public health gains observed immediately after spillover reduction may fade over time as the age structure of immunity gradually re-equilibrates to a reduced force of infection.

Lassa Fever: Critical Review and Prospects for Control.

Lassa Fever is a deadly viral haemorrhagic disease, causing annually several hundreds of deaths in West Africa. This zoonotic disease is primarily transmitted to humans by rodents of the genus Mastomys, even though other rodents reportedly carry the Lassa virus, while secondary interhuman transmission accounts for approximately 20% of cases. Although this disease has been endemic in rural zones of Nigeria, Sierra Leone, Liberfia, and Guinea for hundreds of years, it is also characterised by epidemic outbreaks in the dry season, responsible for heavy death tolls. No licensed vaccine or satisfying treatment is currently available. Disease management is hindered by the incomplete knowledge of the epidemiology and distribution of the disease, resulting from an inadequate health and surveillance system. Additional scientific constraints such as the genetic diversity of the virus and the lack of understanding of the mechanisms of immune protection complexify the development of a vaccine. The intricate socio-economic context in the affected regions, and the lack of monetary incentive for drug development, allow the disease to persist in some of West Africa's poorest communities. The increase in the number of reported cases and in the fatality rate, the expansion of the endemic area, as well as the threat Lassa Fever represents internationally should urge the global community to work on the disease control and prevention. The disease control requires collaborative research for medical countermeasures and tailored public health policies. Lassa Fever, created by the interconnection between animals, humans, and ecosystems, and embedded in an intricate social context, should be addressed with a 'One Health' approach. This article provides an overview of Lassa Fever, focusing on Nigeria, and discusses the perspectives for the control of disease.

Inactivated rabies-based Lassa fever virus vaccine candidate LASSARAB protects nonhuman primates from lethal disease

Lassa fever virus (LASV), a member of the Arenavirus family, is the etiological agent of Lassa fever, a severe hemorrhagic disease that causes considerable morbidity and mortality in the endemic areas of West Africa. LASV is a rodent-borne CDC Tier One biological threat agent and is on the World Health Organization’s (WHO) Priority Pathogen list. Currently, no FDA-licensed vaccines or specific therapeutics are available. Here, we describe the efficacy of a deactivated rabies virus (RABV)-based vaccine encoding the glycoprotein precursor (GPC) of LASV (LASSARAB). Nonhuman primates (NHPs) were administered a two-dose regimen of LASSARAB or an irrelevant RABV-based vaccine to serve as a negative control. NHPs immunized with LASSARAB developed strong humoral responses to LASV-GPC. Upon challenge, NHPs vaccinated with LASSARAB survived to the study endpoint, whereas NHPs in the control group did not. This study demonstrates that LASSARAB is a worthy candidate for continued development.

Deciphering the enigma of Lassa virus transmission dynamics and strategies for effective epidemic control through awareness campaigns and rodenticides

This study aims to formulate a mathematical framework to examine how the Lassa virus spreads in humans of opposite genders. The stability of the model is analyzed at an equilibrium point in the absence of the Lassa fever. The model’s effectiveness is evaluated using real-life data, and all the parameters needed to determine the basic reproduction number are estimated. Sensitivity analysis is performed to pinpoint the crucial parameters significantly influencing the spread of the infection. The interaction between threshold parameters and the basic reproduction number is simulated. Control theory is employed to devise and evaluate strategies, such as awareness campaigns, advocating condom usage, and deploying rodenticides to reduce the possibility of virus transmission efficiently.

Cellular N-myristoyl transferases Are Required for Mammarenavirus Multiplication.

The mammarenavirus matrix Z protein plays critical roles in virus assembly and cell egress, whereas heterotrimer complexes of a stable signal peptide (SSP) together with glycoprotein subunits GP1 and GP2, generated via co-and post-translational processing of the surface glycoprotein precursor GPC, form the spikes that decorate the virion surface and mediate virus cell entry via receptor-mediated endocytosis. The Z protein and SSP undergo N-terminal myristoylation by host cell N-myristoyltransferases (NMT1 and NMT2), and G2A mutations that prevent myristoylation of Z or SSP have been shown to affect Z mediated virus budding and GP2 mediated fusion activity required to complete the virus cell entry process. In the present work, we present evidence that the validated on-target specific pan NMT inhibitor DDD85464 exerts a potent antiviral activity against the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) that correlated with reduced Z budding activity and GP2 mediated fusion activity, as well as proteasome mediated degradation of the Z protein. The potent anti-mammarenaviral activity of DDD85646 was also observed with the hemorrhagic fever causing mammarenaviruses Junin (JUNV) and Lassa (LASV) viruses. Our results support exploration of NMT inhibition as a broad-spectrum antiviral against human pathogenic mammarenaviruses.