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The life cycle of Ebola and Marburg viruses includes a step of the virion envelope fusion with the cell membrane. Here, we analyzed whether the fusion of liposome membranes under the action of fragments of fusion peptides of Ebola and Marburg viruses depends on the composition of lipid vesicles. A fluorescence assay and electron microscopy were used to quantify the fusogenic activity of the virus fusion peptides and to identify the lipid determinants affecting membrane merging. Differential scanning calorimetry of lipid phase transitions revealed alterations in the physical properties of the lipid matrix produced by virus fusion peptides. Additionally, we found that plant polyphenols, quercetin, and myricetin inhibited vesicle fusion induced by the Marburg virus fusion peptide. [ABSTRACT FROM AUTHOR]

The Marburg virus (MARV), the virus responsible for Marburg hemorrhagic fever (MHF), is considered a top-priority pathogen for vaccine development. Recent outbreaks in Equatorial Africa have highlighted the urgency of MARV because of its high fatality rate and historical concerns about potential weaponization. Currently, there are no licensed vaccines for MARV. Existing vaccine candidates rely on attenuated recombinant vesicular stomatitis virus carrying MARV glycoprotein (VSVΔG) or the chimpanzee replication-defective adenovirus 3 vector ChAd3-MARV. Although these platforms provide significant protection in animal models, they face challenges because of their limited thermal stability and the need for cold storage during deployment in resource-poor areas. An alternative approach involves using adjuvanted poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with synthetic peptides representing MHC class I—restricted T cell epitopes. This vaccine platform has demonstrated effectiveness in protecting against SARS-CoV-2 and EBoV disease in animal models and has the advantage of not requiring cold storage and remaining stable at room temperature for over six months. This report outlines the design, manufacturing, and in vivo immunogenicity testing of PLGA microparticle human vaccines designed to prevent Marburg hemorrhagic fever. [ABSTRACT FROM AUTHOR]

Purpose: Emerging and re-emerging viral infections are accountable for fatal outbreaks across the globe. In the light of the COVID-19 catastrophe and mpox exigency, the gaps in prophylactic measures have been envisaged. Emerging and re-emerging infections like poxviruses, Zika, Marburg, Ebola, Hanta, Nipah viruses have further challenged the healthcare sector by putting additional burden on therapeutic and diagnostic limitations. In the present review we also highlighted potential implications of artificial intelligence for long term solutions. Methods: Artificial Intelligence (AI) and Machine Learning (ML)-based models have shown promise in accelerating the discovery of new antivirals or potential vaccine candidates. Deep learning (DL) based algorithms can integrate prodigious global data comprising epidemiology, genomics, pathology and molecular behaviour. Subsequently, support vector machine/ random forest/ neural network guided interpretations can comprehensively compile the available datasets for therapeutic and diagnostic predictions. Results: The present review compiled the various AI-based algorithms and servers which were used for modelling studies as well as prophylactic measures during recent viral outbreaks. The impact of AI on surveillance, outcome prediction, patient monitoring, genomic tracking, clinical assistance, therapeutic screening, drug/ vaccine design and other experimental studies were emphasized. Conclusions: The present review not only highlighted public-health management models but also provide leads in potential therapeutic targets as well as vaccine/ antiviral candidates. To support the context, the issues with existing therapeutic strategies are also overviewed and the prospects were identified. This review discusses a wide range of applications of AI and ML pertaining to the clinical domain. [ABSTRACT FROM AUTHOR]

Abstract Background Marburg virus disease is an acute haemorrhagic fever caused by Marburg virus. Marburg virus is zoonotic, maintained in nature in Egyptian fruit bats, with occasional spillover infections into humans and nonhuman primates. Although rare, sporadic cases and outbreaks occur in Africa, usually associated with exposure to bats in mines or caves, and sometimes with secondary human-to-human transmission. Outbreaks outside of Africa have also occurred due to importation of infected monkeys. Although all previous Marburg virus disease outbreaks have been brought under control without vaccination, there is nevertheless the potential for large outbreaks when implementation of public health measures is not possible or breaks down. Vaccines could thus be an important additional tool, and development of several candidate vaccines is under way. Methods We developed a branching process model of Marburg virus transmission and investigated the potential effects of several prophylactic and reactive vaccination strategies in settings driven primarily by multiple spillover events as well as human-to-human transmission. Linelist data from the 15 outbreaks up until 2022, as well as an Approximate Bayesian Computational framework, were used to inform the model parameters. Results Our results show a low basic reproduction number which varied across outbreaks, from 0.5 [95% CI 0.05–1.8] to 1.2 [95% CI 1.0–1.9] but a high case fatality ratio. Of six vaccination strategies explored, the two prophylactic strategies (mass and targeted vaccination of high-risk groups), as well as a combination of ring and targeted vaccination, were generally most effective, with a probability of potential outbreaks being terminated within 1 year of 0.90 (95% CI 0.90–0.91), 0.89 (95% CI 0.88–0.90), and 0.88 (95% CI 0.87–0.89) compared with 0.68 (0.67–0.69) for no vaccination, especially if the outbreak is driven by zoonotic spillovers and the vaccination campaign initiated as soon as possible after onset of the first case. Conclusions Our study shows that various vaccination strategies can be effective in helping to control outbreaks of MVD, with the best approach varying with the particular epidemiologic circumstances of each outbreak.

Marburg virus (MARV) is one of the filovirus species that cause deadly hemorrhagic fever in humans, with mortality rates up to 90%. Neutralizing antibodies represent ideal candidates to prevent or treat virus disease. However, no antibody has been approved for MARV treatment to date. In this study, we identified a novel human antibody named AF-03 that targeted MARV glycoprotein (GP). AF-03 possessed a high binding affinity to MARV GP and showed neutralizing and protective activities against the pseudotyped MARV in vitro and in vivo. Epitope identification, including molecular docking and experiment-based analysis of mutated species, revealed that AF-03 recognized the Niemann-Pick C1 (NPC1) binding domain within GP1. Interestingly, we found the neutralizing activity of AF-03 to pseudotyped Ebola viruses (EBOV, SUDV, and BDBV) harboring cleaved GP instead of full-length GP. Furthermore, NPC2-fused AF-03 exhibited neutralizing activity to several filovirus species and EBOV mutants via binding to CI-MPR. In conclusion, this work demonstrates that AF-03 represents a promising therapeutic cargo for filovirus-caused disease.

The first-ever Marburg virus disease (MVD) outbreak in Tanzania serves as a stark warning of the vulnerability of the entire world to newly emerging infectious diseases. This article looks at the causes of Tanzania’s susceptibility to MVD, containment efforts, and strategies to stop further outbreaks. The analysis emphasizes the significance of addressing socio-economic variables, environmental issues, and community participation in addition to healthcare infrastructure and surveillance systems for long-term health security. It highlights the requirement for a concerted effort on the part of governments, international organizations, and local communities, as well as ongoing financial support for public health infrastructure. The opinion also urges regional collaboration and coordination, as well as the adoption of a learning attitude to incorporate lessons from this and other outbreaks for enhancing and perfecting public health policies. We can contribute to global efforts to prevent and limit future infectious disease outbreaks and protect the health of communities around the world by adopting a thorough, proactive, and evidence-based strategy.

Marburg Virus is one of the most neglected diseases that dated back to 1967. Prior to the 21st century, the outbreak of the virus was recorded trice, In 1967, 1998 and 2004. Accurate and early detection of pathogenic viruses such as Marburg, Ebola, Zika, Human Immunodeficiency Virus (HIV), Dengue, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) etc. is crucial for treatment and prevention. In the Last 2 decades, scientists relied on molecular diagnostic assays which include antigen-antibody and nucleic acid-based testing approaches for the detection of pathogenic viruses, bacteria, fungi and pathogenic surveillances. Despite the widely used of these assays, they are hindered by several factors which includes high cost, the use of expensive tools, long turnaround time, the use of chemicals and the need for trained personnel. In order to counter some of these challenges, scientists developed Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based biosensor characterized by high specificity. Integration of CRISPR-based biosensor with nanomaterials have shown to increase the performance of the biosensors. Thus, this review provides extensive knowledge on the pathogenicity of Zika and Marburg viruses, conventional diagnosis and the prospect of CRISPR-Cas toolbox in conducting accurate diagnosis of these viruses. The review cover 6 sections which include introduction as section 1, overview of the pathogenicity of Ebola and Marburg viruses in terms of pathology, transmission, number of cases are discussed in section 2, conventional approaches are covered in section 3, CRISPR/Cas systems in both prokaryotic and eukaryotic are overviewed in section 4, the link between CRISPR/Cas system and detection of Ebola and Marburg viruses are presented in section 5, open research and issues are highlighted in section 6 while section 7 covers the concluding remarks.

The 2022 Federation Internationale de Football Association (FIFA) World Cup will take place in Qatar and will be a one-of-a-kind mega-crowd gathering. This is the first time in history that people from all over the world would gather in such a concentrated place. There is a higher chance of spreading zoonotic illnesses from one community to another among those who travel internationally, therefore tourists should be aware of the dangers they may face and take precautions. The public health system of the country hosting the event must be equipped to avoid the spread of zoonotic diseases considering the current global climate. The potential for an increase in cases of COVID-19 and monkeypox is notably heightened by this event. Possible exotic diseases such as the Marburg virus disease could also be spread. Due to Qatar’s inexperience in hosting such major events, it is crucial to invest heavily in training for the early identification of infectious illnesses and the prevention of their spread among event attendees. Visitors to Qatar 2022 should acquire the most up-to-date information available and be aware of the usual precautions that should be followed. Your immunization record must be up to date. Hospitals and other medical facilities in Qatar would be wise to increase their readiness for mass casualty occurrences given that this small location is hosting such an event for the first time. To better meet the health needs of its population, the government of Qatar should promote health advice materials in different languages and keep an adequate supply on hand. The potential for the emergence of zoonotic diseases is briefly reviewed here considering the upcoming FIFA World Cup in 2022.

Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Beyond pre-existing plans prior to the outbreak, BARDA worked with product sponsors to expedite manufacturing of vaccine doses that could be utilized in clinical trials. While the SUDV outbreak has since ended, a new outbreak of MARV disease has emerged. It remains critical that we continue to advance a portfolio of vaccines against SUDV and MARV while also expediting manufacturing activities ahead of, or in parallel if needed, outbreaks. [ABSTRACT FROM AUTHOR]

Background: Outbreaks of Marburg virus disease (MVD) are rare and small in size, with only 18 recorded outbreaks since 1967, only two of which involved more than 100 cases. It has been proposed, therefore, that Phase 3 trials for MVD vaccines should be held open over multiple outbreaks until sufficient end points accrue to enable vaccine efficacy (VE) to be calculated. Here we estimate how many outbreaks might be needed for VE to be estimated. Methods: We adapt a mathematical model of MVD transmission to simulate a Phase 3 individually randomised placebo controlled vaccine trial. We assume in the base case that vaccine efficacy is 70% and that 50% of individuals in affected areas are enrolled into the trial (1:1 randomisation). We further assume that the vaccine trial starts two weeks after public health interventions are put in place and that cases occurring within 10 days of vaccination are not included in VE calculations. Results: The median size of simulated outbreaks was 2 cases. Only 0.3% of simulated outbreaks were predicted to have more than 100 MVD cases. 95% of simulated outbreaks terminated before cases accrued in the placebo and vaccine arms. Therefore the number of outbreaks required to estimate VE was large: after 100 outbreaks, the estimated VE was 69% but with considerable uncertainty (95% CIs: 0%−100%) while the estimated VE after 200 outbreaks was 67% (95% CIs: 42%−85%). Altering base-case assumptions made little difference to the findings. In a sensitivity analysis, increasing R0 by 25% and 50% led to an estimated VE after 200 outbreaks of 69% (95% CIs: 53–85%) and 70% (95% CIs: 59–82%), respectively. Conclusions: It is unlikely that the efficacy of any candidate vaccine can be calculated before more MVD outbreaks have occurred than have been recorded to date. This is because MVD outbreaks tend to be small, public health interventions have been historically effective at reducing transmission, and vaccine trials are only likely to start after these interventions are already in place. Hence, it is expected that outbreaks will terminate before, or shortly after, cases start to accrue in the vaccine and placebo arms.

The Marburg virus (MARV), the virus responsible for Marburg hemorrhagic fever (MHF), is considered a top-priority pathogen for vaccine development. Recent outbreaks in Equatorial Africa have highlighted the urgency of MARV because of its high fatality rate and historical concerns about potential weaponization. Currently, there are no licensed vaccines for MARV. Existing vaccine candidates rely on attenuated recombinant vesicular stomatitis virus carrying MARV glycoprotein (VSVΔG) or the chimpanzee replication-defective adenovirus 3 vector ChAd3-MARV. Although these platforms provide significant protection in animal models, they face challenges because of their limited thermal stability and the need for cold storage during deployment in resource-poor areas. An alternative approach involves using adjuvanted poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with synthetic peptides representing MHC class I—restricted T cell epitopes. This vaccine platform has demonstrated effectiveness in protecting against SARS-CoV-2 and EBoV disease in animal models and has the advantage of not requiring cold storage and remaining stable at room temperature for over six months. This report outlines the design, manufacturing, and in vivo immunogenicity testing of PLGA microparticle human vaccines designed to prevent Marburg hemorrhagic fever.

Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV) and Marburg virus (MARV), are members of the Filoviridae family that can cause severe disease and death in humans and animals. The reemergence of Ebola, Sudan and Marburg virus disease highlight the need for continued availability of safe and effectives vaccines as well as development of new vaccines. While randomized controlled trials using disease endpoints provide the most robust assessment of vaccine effectiveness, challenges to this approach include the unpredictable size, location, occurrence and duration of filovirus disease outbreaks. Thus, other approaches to demonstrating vaccine effectiveness have been considered. These approaches are discussed using examples of preventive vaccines against other infectious diseases. In addition, this article proposes a clinical immunobridging strategy using licensed EBOV vaccines as comparators for demonstrating the effectiveness of filovirus vaccine candidates that are based on the same licensed vaccine platform technology. [ABSTRACT FROM AUTHOR]

Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV) and Marburg virus (MARV), are members of the Filoviridae family that can cause severe disease and death in humans and animals. The reemergence of Ebola, Sudan and Marburg virus disease highlight the need for continued availability of safe and effectives vaccines as well as development of new vaccines. While randomized controlled trials using disease endpoints provide the most robust assessment of vaccine effectiveness, challenges to this approach include the unpredictable size, location, occurrence and duration of filovirus disease outbreaks. Thus, other approaches to demonstrating vaccine effectiveness have been considered. These approaches are discussed using examples of preventive vaccines against other infectious diseases. In addition, this article proposes a clinical immunobridging strategy using licensed EBOV vaccines as comparators for demonstrating the effectiveness of filovirus vaccine candidates that are based on the same licensed vaccine platform technology.

The 2022 Federation Internationale de Football Association (FIFA) World Cup will take place in Qatar and will be a one-of-a-kind mega-crowd gathering. this is the first time in history that people from all over the world would gather in such a concentrated place. there is a higher chance of spreading zoonotic illnesses from one community to another among those who travel internationally, therefore tourists should be aware of the dangers they may face and take precautions. the public health system of the country hosting the event must be equipped to avoid the spread of zoonotic diseases considering the current global climate. the potential for an increase in cases of COVID-19 and monkeypox is notably heightened by this event. Possible exotic diseases such as the Marburg virus disease could also be spread. Due to Qatar's inexperience in hosting such major events, it is crucial to invest heavily in training for the early identification of infectious illnesses and the prevention of their spread among event attendees. Visitors to Qatar 2022 should acquire the most up-to-date information available and be aware of the usual precautions that should be followed. Your immunization record must be up to date. Hospitals and other medical facilities in Qatar would be wise to increase their readiness for mass casualty occurrences given that this small location is hosting such an event for the first time. to better meet the health needs of its population, the government of Qatar should promote health advice materials in different languages and keep an adequate supply on hand. the potential for the emergence of zoonotic diseases is briefly reviewed here considering the upcoming FIFA World Cup in 2022. [ABSTRACT FROM AUTHOR]

This study deals with Bohemian and Moravian students at five Reformed institutes of higher learning in the territory of current Germany and Switzerland in the period of 1575--1620. In particular, it traces their presence at universities in Basel, Heidelberg, and Marburg, and academies in Herborn and Geneva. Each of the selected institutions is introduced in a cameo, which in addition to a brief history of the school mentions also the most important professors in relation to Bohemian and Moravian scholars. This is followed by an analysis of the two groups, i.e., the Bohemian and Moravian scholars, whereby the author follows two factors: social background of the matriculated scholars and changes in peregrination over time. Data pertaining to the individual institutions are then compared and analysed in a separate summary chapter. The study also includes revised lists of Bohemian and Moravian students at the selected schools during the period of interest, i.e., 1575--1620. [ABSTRACT FROM AUTHOR]

Marburg virus disease is a severe viral disease that is often associated with high mortality. The outbreak of the fatal hemorrhagic disease has been reported for the first time in Ghana in 2022, wherein two cases of the disease were reported in hospitals. The World Health Organization has strengthened its ongoing activities by alerting the neighboring nations, deployment of experts in the nation, and increasing the availability of personal protective equipment. The success of sustainable control of the infection lies in the engagement of the community and this essentially requires measures to create awareness about the infection. It is of paramount importance to safeguard the well-being of healthcare professionals and thus each and every one of them should be sensitized and trained about the safety measures. To conclude, Marburg virus disease results in hemorrhagic manifestations, which makes the infected persons highly prone to adverse clinical outcomes. The first outbreak of the infection reported in Ghana is a reminder for international health agencies and public health authorities that we cannot let our guard down and there is an indispensable need to strengthen infection prevention and control measures.

Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Beyond pre-existing plans prior to the outbreak, BARDA worked with product sponsors to expedite manufacturing of vaccine doses that could be utilized in clinical trials. While the SUDV outbreak has since ended, a new outbreak of MARV disease has emerged. It remains critical that we continue to advance a portfolio of vaccines against SUDV and MARV while also expediting manufacturing activities ahead of, or in parallel if needed, outbreaks.

After the Styrian composer Anselm Hüttenbrenner had largely withdrawn from public life, he spent most of his time between the autumn of 1853 and the autumn of 1858 in Maribor (Marburg). In Maribor and its surroundings he found peace of mind and a closeness to nature, devoting himself intensively to compositional and pedagogical activities. He composed numerous lieder on texts by his host Ferdinand von Rast (Hilarius) plus many piano pieces, in addition to orchestral overtures and church music. The article attempts to shed light on this period in Hüttenbrenner’s life, which has not been previously studied.

Ebola virus (EBOV) and Marburg virus (MARV) continue to emerge and cause severe hemorrhagic disease in humans. A comprehensive understanding of the filovirus-host interplay will be crucial for identifying and developing antiviral strategies. The filoviral VP40 matrix protein drives virion assembly and egress, in part by recruiting specific WW domain-containing host interactors via its conserved PPxY late (L) domain motif to positively regulate virus egress and spread. In contrast to these positive regulators of virus budding, a growing list of WW domain-containing interactors that negatively regulate virus egress and spread have been identified, including BAG3, YAP/TAZ, and WWOX. In addition to host WW domain regulators of virus budding, host PPxY-containing proteins also contribute to regulating this late stage of filovirus replication. For example, angiomotin (AMOT) is a multi-PPxY-containing host protein that functionally interacts with many of the same WW domaincontaining proteins that regulate virus egress and spread. In this report, we demonstrate that host WWOX, which negatively regulates egress of VP40 virus-like particles (VLPs) and recombinant vesicular stomatitis virus (VSV) M40 virus, interacts with and suppresses the expression of AMOT. We found that WWOX disrupts AMOT's scaffoldlike tubular distribution and reduces AMOT localization at the plasma membrane via lysosomal degradation. In sum, our findings reveal an indirect and novel mechanism by which modular PPxY-WW domain interactions between AMOT and WWOX regulate PPxY-mediated egress of filovirus VP40 VLPs. A better understanding of this modular network and competitive nature of protein-protein interactions will help to identify new antiviral targets and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Clinical vaccine development and regulatory approval generally occurs in a linear, sequential manner: Phase 1: safety, immunogenicity; Phase 2: immunogenicity, safety, dose ranging, and preliminary efficacy; Phase 3: definitive efficacy, safety, lot consistency; and following regulatory approval, Phase 4: post-marketing safety and effectiveness. For candidate filovirus vaccines, where correlates of protection have not been identified, and phase 2 and 3 efficacy of disease prevention trials untenable, large and/or protracted, each trial may span decades, with full licensure expected only after several decades of development. Given the urgent unmet need for new Marburg virus and Ebola Sudan virus vaccines, the Sabin Vaccine Institute hosted a key stakeholder virtual meeting in May 2021 to explore the possibility of licensure by use of an "animal rule-like" licensure process, based on a risk/benefit assessment specific to regional needs and informed by epidemiology. This may be appropriate for diseases where there are no or limited treatment options, and those prone to sporadic outbreaks with high rates of transmission, morbidity, and mortality. The discussion focused on two contexts: licensure within the Ugandan regulatory environment, a high burden country where Ebola vaccine trials are ongoing, and licensure by the United States FDA—a well-resourced regulatory agency. [ABSTRACT FROM AUTHOR]

The 2014–2016 Ebola virus epidemic in West Africa triggered extensive investments from public and private partners in an attempt to slow the spread of disease and bring the outbreak under control. This significantly accelerated the pace of development of countermeasures against Zaire ebolavirus that enabled vaccines to be a part of an effective response to the most recent 2018–2019 outbreak in the Democratic Republic of the Congo. However, there remain urgent and unmet needs for medical countermeasures against other members of the Filoviridae family that cause viral hemorrhagic fevers. To improve the national and global preparedness posture for viral hemorrhagic fevers, a renewed emphasis is being placed on developing vaccines for filoviruses other than Zaire ebolavirus. Here we discuss lessons learned from the West Africa epidemic and how those lessons apply to the development of vaccine candidates for other filoviruses, specifically Sudan ebolavirus and Marburg virus. This commentary will highlight some of the key product development gaps to address in preparation for future disease outbreaks caused by these viruses.

Multiple agents in the family Filoviridae (filoviruses) are associated with sporadic human outbreaks of highly lethal disease, while others, including several recently identified agents, possess strong zoonotic potential. Although viral glycoprotein (GP)-specific monoclonal antibodies have demonstrated therapeutic utility against filovirus disease, currently FDA-approved molecules lack antiviral breadth. The development of broadly neutralizing antibodies has been challenged by the high sequence divergence among filovirus GPs and the complex GP proteolytic cleavage cascade that accompanies filovirus entry. Despite this variability in the antigenic surface of GP, all filoviruses share a site of vulnerability—the binding site for the universal filovirus entry receptor, Niemann-Pick C1 (NPC1). Unfortunately, this site is shielded in extracellular GP and only uncovered by proteolytic cleavage by host proteases in late endosomes and lysosomes, which are generally inaccessible to antibodies. To overcome this obstacle, we previously developed a 'Trojan horse' therapeutic approach in which engineered bispecific antibodies (bsAbs) coopt viral particles to deliver GP:NPC1 interaction-blocking antibodies to their endo/lysosomal sites of action. This approach afforded broad protection against members of the genus Ebolavirus but could not neutralize more divergent filoviruses. Here, we describe next-generation Trojan horse bsAbs that target the endo/lysosomal GP:NPC1 interface with pan-filovirus breadth by exploiting the conserved and widely expressed host cation-independent mannose-6-phosphate receptor for intracellular delivery. Our work highlights a new avenue for the development of single therapeutics protecting against all known and newly emerging filoviruses. [ABSTRACT FROM AUTHOR]

Multiple agents in the family Filoviridae (filoviruses) are associated with sporadic human outbreaks of highly lethal disease, while others, including several recently identified agents, possess strong zoonotic potential. Although viral glycoprotein (GP)-specific monoclonal antibodies have demonstrated therapeutic utility against filovirus disease, currently FDA-approved molecules lack antiviral breadth. The development of broadly neutralizing antibodies has been challenged by the high sequence divergence among filovirus GPs and the complex GP proteolytic cleavage cascade that accompanies filovirus entry. Despite this variability in the antigenic surface of GP, all filoviruses share a site of vulnerability—the binding site for the universal filovirus entry receptor, Niemann-Pick C1 (NPC1). Unfortunately, this site is shielded in extracellular GP and only uncovered by proteolytic cleavage by host proteases in late endosomes and lysosomes, which are generally inaccessible to antibodies. To overcome this obstacle, we previously developed a ‘Trojan horse’ therapeutic approach in which engineered bispecific antibodies (bsAbs) coopt viral particles to deliver GP:NPC1 interaction-blocking antibodies to their endo/lysosomal sites of action. This approach afforded broad protection against members of the genus Ebolavirus but could not neutralize more divergent filoviruses. Here, we describe next-generation Trojan horse bsAbs that target the endo/lysosomal GP:NPC1 interface with pan-filovirus breadth by exploiting the conserved and widely expressed host cation-independent mannose-6-phosphate receptor for intracellular delivery. Our work highlights a new avenue for the development of single therapeutics protecting against all known and newly emerging filoviruses.

Tumefactive demyelination (TD) can be a challenging scenario for clinicians due to difficulties distinguishing it from other conditions, such as neoplasm or infection; or with managing the consequences of acute lesions, and then deciding upon the most appropriate longer term treatment strategy. The authors review the literature regarding TD covering its clinic-radiological features, association with multiple sclerosis (MS), and its differential diagnosis with other neuroinflammatory and non-inflammatory mimicking disorders with an emphasis on atypical forms of demyelination including acute disseminated encephalomyelitis (ADEM), MOG antibody-associated demyelination (MOGAD) and neuromyelitis spectrum disorders (NMOSD). We also review the latest in the acute and long-term treatment of TD. It is important that the underlying cause of TD be determined whenever possible to guide the management approach which differs between different demyelinating and other inflammatory conditions. Improved neuroimaging and advances in serum and CSF biomarkers should one day allow early and accurate diagnosis of TD leading to better outcomes for patients. [ABSTRACT FROM AUTHOR]

This article calls attention to an unpublished account of the 1954 General Meeting of SNTS in Marburg, written by C. K. Barrett. The interesting part of Barrett's account is its picture of Rudolf Bultmann who, after the evening sessions, with a group of colleagues withdrew to a pavement café at the Marktplatz and sat there 'at the head in undisputed preeminence'. [ABSTRACT FROM AUTHOR]

Two philosophical positions adopted by Soloveitchik in his doctoral dissertation continued to inform his Jewish philosophical writings throughout his career. The first position, epistemological pluralism, stands behind Soloveitchik's approach to the religious view of causality and repentance in his writings during the 1940s–1960s. It also grounds his consistent use of the dialectical method. The second position, the eternal mystery of the unknown, comes from the Marburg neo-Kantian Paul Natorp; this idea is a consistent thread throughout Soloveitchik's writings and a foundation of his existentialist writings through the late 1970s. The conclusion suggests how these two positions might be related to one another. [ABSTRACT FROM AUTHOR]

Marburg virus disease is a severe viral disease that is often associated with high mortality. The outbreak of the fatal hemorrhagic disease has been reported for the first time in Ghana in 2022, wherein two cases of the disease were reported in hospitals. The World Health Organization has strengthened its ongoing activities by alerting the neighboring nations, deployment of experts in the nation, and increasing the availability of personal protective equipment. The success of sustainable control of the infection lies in the engagement of the community and this essentially requires measures to create awareness about the infection. It is of paramount importance to safeguard the well‑being of healthcare professionals and thus each and every one of them should be sensitized and trained about the safety measures. To conclude, Marburg virus disease results in hemorrhagic manifestations, which makes the infected persons highly prone to adverse clinical outcomes. The first outbreak of the infection reported in Ghana is a reminder for international health agencies and public health authorities that we cannot let our guard down and there is an indispensable need to strengthen infection prevention and control measures. [ABSTRACT FROM AUTHOR]