Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 ...Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 during concurrent outbreaks in Marburg and Frankfurt,Germany,and in Belgrade,Serbia,linked to laboratory use of African green monkeys imported from Uganda.Subsequent outbreaks and isolated cases have been reported in various African countries,including Angola,the Democratic Republic of the Congo,Equatorial Guinea,Ghana,Guinea,Kenya,Rwanda,South Africa(in an individual with recent travel to Zimbabwe),Tanzania,and Uganda.Initial human MVD infections typically occur due to prolonged exposure to mines or caves inhabited by Rousettus aegyptiacus fruit bats,the natural hosts of the virus.展开更多
The Marburg virus(MARV)is a dangerous infection that causes a deadly sickness known as MARV disease.This severe hemorrhagic fever is a major concern for people all over the world.Since the initial identification in 19...The Marburg virus(MARV)is a dangerous infection that causes a deadly sickness known as MARV disease.This severe hemorrhagic fever is a major concern for people all over the world.Since the initial identification in 1967 during simultaneous outbreaks in Germany and Serbia,MARV has caused recurrent epidemics predominantly in sub-Saharan Africa with fatality rates ranging from 24%to 90%as a result of differences in virus strains,healthcare infrastructure,and the quality of patient treatment.Like Ebola virus,MARV causes a viral hemorrhagic fever identified in some of the same principles of clinical and epidemiological concern.However,MARV has unique biologic characteristics that require specialized research and response by public health and among researchers.Diagnosis relies on molecular tools such as real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay,as well as clinical and epidemiological assessments.Despite advancements in understanding MARV biology,no vaccines or antiviral therapies have been approved,with treatment limited to supportive care.Experimental therapeutics,monoclonal antibodies,RNA-based drugs,and adenovirus-based vaccines,show promise but require further validation.Current efforts in outbreak containment include surveillance,rapid diagnostics,case isolation,and safe burial practices.However,gaps in understanding MARV pathogenesis,limited diagnostic tools,and the absence of regulatoryapproved vaccines underscore the urgent need for global collaboration and investment in research.Bridging these gaps is critical to mitigating the public health impact of MARV,ensuring effective response strategies for future outbreaks.展开更多
Background: The Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD). This filovirus first appeared in 1967 and has since caused several outbreaks with case fatality rates between 23% and 90%. Th...Background: The Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD). This filovirus first appeared in 1967 and has since caused several outbreaks with case fatality rates between 23% and 90%. The earliest cases of MVD are thought to be caused by exposure to an infected animal, either a reservoir host (some bat species, e.g., Rousettus aegyptiacus) or a spill-over host, such as non-human primates. The virus is spread between people by direct contact with blood or other bodily fluids (including saliva, sweat, faeces, urine, tears, and breast milk) from infected individuals. Despite the high fatality rate, the Marburg virus has no vaccine or drug treatment. Recent outbreaks of the virus in 2023 in Tanzania and Equatorial Guinea have reignited the need to develop effective therapeutics, especially in the wake of the COVID-19 pandemic. Purpose: This review seeks to highlight the drug discovery efforts aimed at developing vaccines or possible treatments as potential therapeutics. Several existing antiviral agents are being probed, and vaccines are in pre-clinical and clinical stages. Natural products are also an important source of possible drugs or lead compounds and when coupled with computational techniques, these strategies offer possible therapeutics for the Marburg virus, especially in Africa, which has a high disease burden. Methods: Using the search engines Google Scholar and PubMed;keywords e.g. Marburg virus, Marburg treatments, Marburg virus drug discovery were utilized. Several results were yielded, and articles published in recent years were accepted into the final list.Results and Conclusion: This study shows there is a growing interest in therapeutics for the Marburg virus, especially with the recent outbreaks and pandemic preparedness. Initiatives that to support vaccine development and access like the MARVAC consort time are critical to fighting this public health threat.展开更多
The Marburg virus(MARV),belonging to the Filoviridae family,poses a significant global health threat,emphasizing the urgency to develop Marburg virus-like particle(VLP)vaccines for outbreak mitigation.The virus's ...The Marburg virus(MARV),belonging to the Filoviridae family,poses a significant global health threat,emphasizing the urgency to develop Marburg virus-like particle(VLP)vaccines for outbreak mitigation.The virus's menacing traits accentuate the need for such vaccines,which can be addressed by VLPs that mimic its structure safely,potentially overcoming past limitations.Early Marburg vaccine endeavors and their challenges are examined in the historical perspectives section,followed by an exploration of VLPs as transformative tools,capable of eliciting immune responses without conventional risks.Noteworthy milestones and achievements in Marburg VLP vaccine development,seen through preclinical and clinical trials,indicate potential cross-protection.Ongoing challenges,encompassing durability,strain diversity,and equitable distribution,are addressed,with proposed innovations like novel adjuvant,mRNA technology,and structure-based design poised to enhance Marburg VLP vaccines.This review highlights the transformative potential of Marburg VLPs in countering the virus,showcasing global collaboration,regulatory roles,and health equity for a safer future through the harmonious interplay of science,regulation,and global efforts.展开更多
Background:In the management of patients with MARV infection,this review article focuses on the potential protective effects of black seeds(Nigella sativa).Methods:To find studies that evaluated various effects of bla...Background:In the management of patients with MARV infection,this review article focuses on the potential protective effects of black seeds(Nigella sativa).Methods:To find studies that evaluated various effects of black seeds(N.sativa)related to signs and symptoms of MARV infection,reference lists and databases such as Medline/Pubmed/PMC,Google Scholar,Science Direct,Ebsco,Scopus,Web of Science,and Embase were searched.Results:In numerous clinical,animal,in-vitro,in-vivo,and in-ovo studies,black seeds(N.sativa)have demonstrated potential antiviral,anti-inflammatory,antioxidant,immunomodulatory,and hepatoprotective properties that may aid in the treatment of MARV-infected patients.Conclusion:In the initial generalization phase of MARV infection,patients may use black seeds(N.sativa)as an adjunctive therapy in addition to symptomatic treatment and supportive care.Future randomized controlled clinical trials would confirm N.sativa’s efficacy and safety in MARV-infected patients.展开更多
The Angolan strain of Marburg virus （MARV/Ang） can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previo...The Angolan strain of Marburg virus （MARV/Ang） can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice （MARV/Ang-MA）, with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate （NHP） model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs （MARV/Ang- GA）. Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1x10-1 TCID50 （median tissue culture infective dose）. Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.展开更多
The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates （NHPs）, causing severe hemorrhagic fevers with high fatali...The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates （NHPs）, causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.展开更多
Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for t...Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.展开更多
文摘Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 during concurrent outbreaks in Marburg and Frankfurt,Germany,and in Belgrade,Serbia,linked to laboratory use of African green monkeys imported from Uganda.Subsequent outbreaks and isolated cases have been reported in various African countries,including Angola,the Democratic Republic of the Congo,Equatorial Guinea,Ghana,Guinea,Kenya,Rwanda,South Africa(in an individual with recent travel to Zimbabwe),Tanzania,and Uganda.Initial human MVD infections typically occur due to prolonged exposure to mines or caves inhabited by Rousettus aegyptiacus fruit bats,the natural hosts of the virus.
文摘The Marburg virus(MARV)is a dangerous infection that causes a deadly sickness known as MARV disease.This severe hemorrhagic fever is a major concern for people all over the world.Since the initial identification in 1967 during simultaneous outbreaks in Germany and Serbia,MARV has caused recurrent epidemics predominantly in sub-Saharan Africa with fatality rates ranging from 24%to 90%as a result of differences in virus strains,healthcare infrastructure,and the quality of patient treatment.Like Ebola virus,MARV causes a viral hemorrhagic fever identified in some of the same principles of clinical and epidemiological concern.However,MARV has unique biologic characteristics that require specialized research and response by public health and among researchers.Diagnosis relies on molecular tools such as real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay,as well as clinical and epidemiological assessments.Despite advancements in understanding MARV biology,no vaccines or antiviral therapies have been approved,with treatment limited to supportive care.Experimental therapeutics,monoclonal antibodies,RNA-based drugs,and adenovirus-based vaccines,show promise but require further validation.Current efforts in outbreak containment include surveillance,rapid diagnostics,case isolation,and safe burial practices.However,gaps in understanding MARV pathogenesis,limited diagnostic tools,and the absence of regulatoryapproved vaccines underscore the urgent need for global collaboration and investment in research.Bridging these gaps is critical to mitigating the public health impact of MARV,ensuring effective response strategies for future outbreaks.
文摘Background: The Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD). This filovirus first appeared in 1967 and has since caused several outbreaks with case fatality rates between 23% and 90%. The earliest cases of MVD are thought to be caused by exposure to an infected animal, either a reservoir host (some bat species, e.g., Rousettus aegyptiacus) or a spill-over host, such as non-human primates. The virus is spread between people by direct contact with blood or other bodily fluids (including saliva, sweat, faeces, urine, tears, and breast milk) from infected individuals. Despite the high fatality rate, the Marburg virus has no vaccine or drug treatment. Recent outbreaks of the virus in 2023 in Tanzania and Equatorial Guinea have reignited the need to develop effective therapeutics, especially in the wake of the COVID-19 pandemic. Purpose: This review seeks to highlight the drug discovery efforts aimed at developing vaccines or possible treatments as potential therapeutics. Several existing antiviral agents are being probed, and vaccines are in pre-clinical and clinical stages. Natural products are also an important source of possible drugs or lead compounds and when coupled with computational techniques, these strategies offer possible therapeutics for the Marburg virus, especially in Africa, which has a high disease burden. Methods: Using the search engines Google Scholar and PubMed;keywords e.g. Marburg virus, Marburg treatments, Marburg virus drug discovery were utilized. Several results were yielded, and articles published in recent years were accepted into the final list.Results and Conclusion: This study shows there is a growing interest in therapeutics for the Marburg virus, especially with the recent outbreaks and pandemic preparedness. Initiatives that to support vaccine development and access like the MARVAC consort time are critical to fighting this public health threat.
文摘The Marburg virus(MARV),belonging to the Filoviridae family,poses a significant global health threat,emphasizing the urgency to develop Marburg virus-like particle(VLP)vaccines for outbreak mitigation.The virus's menacing traits accentuate the need for such vaccines,which can be addressed by VLPs that mimic its structure safely,potentially overcoming past limitations.Early Marburg vaccine endeavors and their challenges are examined in the historical perspectives section,followed by an exploration of VLPs as transformative tools,capable of eliciting immune responses without conventional risks.Noteworthy milestones and achievements in Marburg VLP vaccine development,seen through preclinical and clinical trials,indicate potential cross-protection.Ongoing challenges,encompassing durability,strain diversity,and equitable distribution,are addressed,with proposed innovations like novel adjuvant,mRNA technology,and structure-based design poised to enhance Marburg VLP vaccines.This review highlights the transformative potential of Marburg VLPs in countering the virus,showcasing global collaboration,regulatory roles,and health equity for a safer future through the harmonious interplay of science,regulation,and global efforts.
文摘Background:In the management of patients with MARV infection,this review article focuses on the potential protective effects of black seeds(Nigella sativa).Methods:To find studies that evaluated various effects of black seeds(N.sativa)related to signs and symptoms of MARV infection,reference lists and databases such as Medline/Pubmed/PMC,Google Scholar,Science Direct,Ebsco,Scopus,Web of Science,and Embase were searched.Results:In numerous clinical,animal,in-vitro,in-vivo,and in-ovo studies,black seeds(N.sativa)have demonstrated potential antiviral,anti-inflammatory,antioxidant,immunomodulatory,and hepatoprotective properties that may aid in the treatment of MARV-infected patients.Conclusion:In the initial generalization phase of MARV infection,patients may use black seeds(N.sativa)as an adjunctive therapy in addition to symptomatic treatment and supportive care.Future randomized controlled clinical trials would confirm N.sativa’s efficacy and safety in MARV-infected patients.
基金supported by the Public Health Agency of Canada(PHAC)partially supported by the NIH and CIHR grants to X.G.Qiu(U19 AI109762-1 and CIHR-IER-143487,respectively)+1 种基金grants from the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘The Angolan strain of Marburg virus （MARV/Ang） can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice （MARV/Ang-MA）, with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate （NHP） model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs （MARV/Ang- GA）. Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1x10-1 TCID50 （median tissue culture infective dose）. Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.
基金supported by the Public Health Agency of Canada(PHAC)partially supported by the NIH and CIHR grants to X.G.Qiu(U19 AI109762-1 and CIHR-IER-143487,respectively)+1 种基金the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates （NHPs）, causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.
基金supported by Important National Science & Technology Specific Projects (2012ZX10004403)
文摘Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.
