The Marburg virus (MV) has emerged as a significant global threat, instigating multiple fatal outbreaks with a considerable mortality rate since its discovery and characterization in 1967. Its initial appearance spanned regions including Marburg, Frankfurt (Germany), Yugoslavia (now Serbia), and Belgrade, with Africa primarily bearing the brunt of its impact (Brauburger et al., 2012). According to the National Institute of Allergy and Infectious Diseases, the main cause of MVD is Marburg virus (Bente et al., 2009). The virus’s nomenclature stems from the city where it is devastating effects were most pronounced, resulting in seven deaths among 31 early patients (Brauburger et al., 2012). Investigation subsequently unveiled the virus’s origin in imported Ugandan green African monkeys (Gear et al., 1975). Contrary to the belief that MV posed a lesser threat, significant outbreaks in the Democratic Republic of the Congo (DRC) from 1998 to 2000 and in Angola from 2004 to 2005 demonstrated a fatality rate of 83% and 90%, respectively, dispelling this notion (Bausch et al., 2006; Qiu et al., 2014). Different variants were connected to the outbreak in the DRC, but just one version spread from person to person in Angola (Bertherat et al., 1999; Bausch et al., 2006). By 2008, reported MV cases surged to 452, with 368 confirmed deaths, raising concerns of underreporting (Brauburger et al., 2012). Despite receiving less media attention than its Filoviridae counterparts, MV’s elevated fatality rates underscore its significance. Recent cases in Guinea, Ghana, and the ongoing Equatorial Guinea outbreak accentuate the necessity for continuous surveillance and containment. The latter reported a swift succession of deaths, and Tanzania also reported fatalities attributed to the virus, highlighting the ongoing threat (Manohar et al., 2023). MVD’s impact spans hemorrhagic fever and organ dysfunction in both humans and non-human primates, affecting the liver, spleen, brain, kidneys, and causing coagulation anomalies (Mehedi et al., 2011; van Paassen et al., 2012). As a member of the Marburg virus genus within the Filoviridae family and Mononegavirales order, MV comprises a distinct species (Bukreyev et al., 2014). Its zoonotic connection to the Egyptian fruit bat (Rousettus aegyptiacus) and human-to-human transmission parallel other Ebola viruses, such as Sudan virus, Bundibugyo virus, and EBOV. Ongoing research has elucidated MV’s natural sources, including Hipposideros caffer, in tandem with Rousettus aegyptiacus (Towner et al., 2009). With an average incubation period of 5 to 10 days, ranging from 3 to 21 days, the virus infiltrates immune cells like monocytes, macrophages, and dendritic cells via compromised skin or mucosal surfaces. It initiates replication in the spleen, liver, and secondary lymphoid organs before propagating to hepatocytes, endothelial cells, fibroblasts, and epithelial cells. Additionally, it thwarts interferon type I (IFN-1) production (Yu et al., 2021). This review explores the evolutionary course of MVD outbreaks, succinctly delineating the virus’s structure and genome, elucidating MV’s origins, and detailing its diverse transmission modes among humans and non-human sources. We comprehensively examine MVD’s genesis through scrutinizing pathophysiology, cellular tropism, immune evasion, and critical host injury sites. Additionally, this overview encompasses current clinical data and treatments, underscoring the vital need for robust research to foster effective drugs and vaccines. By deepening comprehension of the virus’s historical progression and infection mechanisms, this review strengthens defenses against MV disease, driving the innovation of therapeutic agents and vaccines, thus supporting future researchers in countering this enduring health threat.

The Marburg virus (MV) exhibits an enveloped and pleomorphic structure, displaying uniform diameter but variable length filamentous, non-segmented, rod-like, cobra-like, circular/annular, and branched particles (Chakraborty et al., 2022; Islam et al., 2023a). Its viral genome encompasses seven open reading frames (ORFs), namely nucleoprotein (NP), virion protein 35 (VP35), VP40, VP30, VP24, glycoprotein (GP), and large viral polymerase, all characterized as single-stranded negative-sense RNA (-ssRNA; Zhao et al., 2022). The non-coding regions of these seven genes contain cis-acting elements implicated in DNA replication, transcription, and packaging (Feldmann et al., 1992; Sanchez et al., 1993). The 3′ and 5′ ends of these genes possess unusually long non-coding nucleotide sequences and highly conserved transcription start and stop signals (Feldmann et al., 1992; Sanchez et al., 1993). Intergenic regions separate all MV genes except two, ranging from 4 to 97 nucleotides in length, and the transcription start and stop signals of the VP24 and VP30 genes share an overlapping sequence of five nucleotides (UAAUU). The nucleocapsid complex, comprising structural proteins NP, VP35, VP30, and L, envelops the MV genome (Becker et al., 1998). VP35, acting as a polymerase cofactor, and L, functioning as an RNA-dependent RNA polymerase, are essential for replication and transcription of viral genomes (Mühlberger et al., 1999). The host-derived membrane layer of MV is regularly spiked, where highly glycosylated protein (GP) plays a key role in binding to receptive host cells (Feldmann et al., 1991). VP40, responsible for budding and binding to the matrix and nucleocapsid, constitutes the inner matrix of a virion (Kolesnikova et al., 2004; Swenson et al., 2004). The interaction of the protein VP24 with the membrane NP and other cell membranes is vital for the release of virion progeny. Table 1 provides an overview of the characteristics and functions of the proteins in MV (Bamberg et al., 2005). Phylogenetic analysis of Marburg virus sequences has been conducted to ascertain sequence cohesion and identify splits between sequences of particular interest and well-known sequences that exhibit unexpectedly deep divergence (Peterson and Holder, 2012). From cDNA clones made from genomic RNA and mRNA, the first 3,000 nucleotides of the Marburg virus genome were identified (Sanchez et al., 1992). There is up to 21% nucleotide diversity among previously characterized East African strains of the Marburg virus, according to partial Marburg virus RNA sequence study (Towner et al., 2006). Serial passages of Marburg virus resulted in a single mutation in the region encoding the glycoprotein (GP; Alfson et al., 2018). To clarify the relationship between various Marburg virus strains, phylogenetic analysis of full-length or partial genomes of Marburg viruses obtained from people or bats has been carried out (Towner et al., 2009). Phylogenetic analysis showed the 2021 Guinean Marburg virus’ relationship to strains from the 2004–2005 Marburg virus outbreak in Angola, which are related to Marburg virus sequences obtained from bats in Sierra Leone (2017–2018). The viral genome sequence of the 2021 Guinean Marburg virus was recovered to 99.3% (Magassouba, 2021). Sequential mouse passaging and cell-culture adaption during deep sequencing of the Marburg virus genome have shown significant changes over time (Wei et al., 2017). An analysis was performed on the sequencing data to identify sites in viral mRNAs (Shabman et al., 2014). Structural and functional studies on the Marburg virus GP2 fusion loop have also been conducted (Liu et al., 2015). Marburg virus has been subjected to mutational and phylogenetic analysis, and the genome has been sequenced to identify changes over time shown in Figure 1 (Mühlberger, 2007).

The fruit bat species Rousettus aegyptiacus is the most important natural source of MV infection. In addition, some Chiroptera and Hipposideros caffer may act as infectious agents. There are several ways in which MV strains can be transmitted from bat to bat. Recent research found MV in rectal, oral, and urine samples from infected bats as well as in blood and oral samples from bats that had come into contact with humans. According to this research, MV is horizontally transmitted from infected bats to bat contacts (Schuh et al., 2017). The findings of the previous study showed that MV was present in the tissues of the lungs, intestines, kidneys, bladder, salivary glands, and female reproductive tract of immunized bats, supporting the hypothesis that MV transmission might occur (Amman et al., 2012) both vertically and horizontally in reservoirs. It has also been suggested that bats could spread the illness to one another by bites (Amman et al., 2015), sexual contact (Amman et al., 2012), or hematophagous arthropods (Schuh et al., 2017). Direct contact (injured skin or mucous membranes) with the blood and other bodily fluids of infected people (urine, saliva, feces, vomit, breast milk, amniotic fluid, and semen) or indirect contact with contaminated surfaces and materials, such as contaminated clothing, bedding, and medical equipment, are the two main methods of interpersonal transmission after infection. Infection may happen if sick people are buried (Schwartz, 2019). Infected animals, particularly bushmeat (such as monkeys, chimpanzees, forest antelopes, and bats), whether alive or dead, can also spread the disease to humans (Figure 3; WHO, 2021a). Bushmeat consumption has been linked to Ebola virus (EBOV) outbreaks (Malik et al., 2023). Because numerous bushmeat species, including chimpanzees and forest antelope, are vulnerable to virus multiplication and consumption following infection (Heeney, 2015), they are regarded as intermediate hosts. There is growing concern about the persistence of filovirus in the testis as a potential route of transmission. Experimental trials have identified persistent MV infection of the immunoprivileged testicular tubules in male monkeys (Coffin et al., 2018). During the 1967 MV outbreak, the first possible case of sexual transmission was found. Two months after the recovery of a male patient, symptoms appeared in his wife, which were confirmed by the detection of MV antigen in his semen (Feldmann, 2018). Simultaneous testing of nine other convalescents for MV did not detect virus or viral antigen (Slenczka, 2017). In pregnant women, filovirus infection is usually more severe than in nonpregnant women, which may be due to decreased immune function or placental involvement (Brainard et al., 2016). Based on case reports, viral titers have been found in placental tissue, suggesting that hematogenous transplacental transmission is the most typical route of fetal infection (Bebell and Riley, 2015). Despite the high rates of pregnancy mortality, there is no proof that pregnant women are more prone to contracting filovirus than other people (Jamieson et al., 2014). Pregnant women who have MVD have an increased risk of stillbirths and spontaneous abortions (Schwartz, 2019). Little information is available on the effects of MVD infection in infants. There have been reports of several MVD clusters in newborns, some of whom had very mild symptoms (Borchert et al., 2002). MV can be present in the blood, organs, and tissues of sick or recovering individuals, suggesting that the virus can be transmitted through transfusion and transplantation. Filoviruses can survive for a very long time in liquid or dried materials (Piercy et al., 2010). They are inactivated by gamma irradiation, heating to 60°C for 60–75 min, or boiling for 5 min and are sensitive to fatty solvents, sodium hypochlorite, and other disinfectants (Kuhn, 2008; Feldmann et al., 2019).

Marburg virus disease (MVD) has an incubation period of two to 21 days. According to the World Health Organization (WHO), high fever, severe malaise, and headache are some of the sudden symptoms associated with Marburg virus infection. Patients frequently complain of muscle pain and pains at the same time. Patients may experience severe watery diarrhea, cramping in the stomach, nausea, and vomiting on the third day. Up to a week may pass during the phase of diarrhea. Patients frequently exhibit a characteristic appearance during this stage that is characterized by sunken eyes, indifferent facial expressions, and extreme sluggishness. Within 2 to 7 days of the onset of symptoms, a non-itchy rash commonly develops (Elsheikh et al., 2023). Hemorrhagic signs often appear 5 to 7 days after the initial episode, with fatal cases showing several sites of hemorrhage. Bleeding from the gums, nasal passages, and vagina usually accompany fresh blood in vomitus and feces. The problem of spontaneous bleeding at venipuncture sites is particularly difficult. High fevers characterize the illness’s severe stage. Involvement with the central nervous system might result in confusion, irritation, and violence. In the later stages of the illness, occasional observations of orchitis, which is defined by inflammation of one or both testicles, have been made (around day 15). Most frequently, death happens 8 to 9 days after the onset, generally after a serious bout of blood loss and a subsequent shock (Elsheikh et al., 2023). Direct contact with the blood, secretions, organs, or other bodily fluids of infected people, as well as with surfaces and objects contaminated with these fluids, can result in human-to-human transmission of the Marburg virus. This contact can happen through cuts, scrapes, or other breaks in the skin or mucous membranes. Exposure to fruit bat species can also cause transmission (Elsheikh et al., 2023). An alternative classification of MV clinical features includes a “Generalization Phase,” which is characterized by flu-like symptoms and rash, an “Early Organ Phase,” which involves manifestations in specific organs, like encephalitis or hemorrhages, and a “Late Organ/Convalescence Phase,” which is characterized by multiorgan failure, shock, coma, and either death or recovery. These phases, in that order, correspond to the first 4 days, the next 9 days, and the time after day 13 (Asad et al., 2020).

MVD models, and lab animals can all be used to study host pathophysiology and immune responses, as is widely recognized. Currently, NHPs (mainly cynomolgus and rhesus monkeys, African vervet monkeys, and baboons), hamsters, guinea pigs, and mice have been used to establish four MV disease models. NHPs are the “gold standard” among these models because to their great susceptibility to MV infections, which are almost always fatal, and their specific clinical traits that are like those of human infections. Furthermore, it has been demonstrated (Bente et al., 2009), that NHPs can directly transmit the MV virus through close contact. In the Kenyan case from 1987, MV infection was found in the peripheral blood mononuclear cell population of infected macaques using immunohistochemical, electron microscopy, and flow cytometric investigations (Mehedi et al., 2011). These studies also identified viral antigen and virions in both circulating and tissue-associated macrophages. Thus, the idea that the mononuclear phagocytic system—which consists of macrophages, monocytes, Kupffer cells, and dendritic cells—is the first cell type that MV infection targets—has been put forth (Brauburger et al., 2012). The lymph nodes, liver, and spleen all displayed the most severe necrotic lesions. Reticuloendothelial cells are abundant in the tissues, allowing infected cells to spread and infect more organs. At the organ level, the liver is a key site for MV replication, and the virus preferentially targets lymphoid tissues there (Shifflett and Marzi, 2019). There has been monocytoidal, plasma cellular alteration in the lymphatic tissue. Sites of necrosis also contain basophilic entities, either in the form of inclusion bodies in parenchymal cells or near necrotic cells. The other organs, on the other hand, are all affected by infection and show pathological changes, such as isolated or widespread necrosis without obvious inflammatory responses. Patients on MARD typically experience proteinuria, a symptom of renal failure. Grossly pale, swollen, and exhibiting significant parenchymal deterioration as well as indications of tubular insufficiency, the injured kidneys are also enlarged. Plasma cells and monocytes are prevalent in the mucous membranes of the stomach and intestines. Alveolar macrophages are found in hemorrhagic, obstructed alveoli in the lungs, and since fibrin surrounds them, these alveoli occasionally stain with viral antigen. In addition to necrosis (Shifflett and Marzi, 2019). The crimson pulp of the spleen, the lymph nodes’ follicles and medulla, as well as the lymphocyte count, are all noticeably necrosed in humans. Surprisingly, bystander apoptosis promotes lymphocyte loss rather than virus infection of cells. Aspartate aminotransferase, alanine aminotransferase, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase rise are liver tests that are suggestive of MV infection because the asialoglycoprotein receptor, a receptor specific to the liver, can boost these enzymes. Given that the liver produces multiple clotting factors, the pathological alterations to the liver are probably a contributing factor to the abnormalities in coagulation seen following MV infection. Severe MARD patients that undergo multiorgan failure do so as a result of the fatal virus’s increased mass effect. A decrease in the production of the steroid-synthesizing enzyme, involvement of the adrenal gland, and its failure all increase the risk of hypotension and hypovolemia, which finally result in shock (Figure 4; Mehedi et al., 2011). The symptoms of this toxic hemorrhagic fever, which have nothing to do with jaundice, include hemorrhagic diatheses in the skin and mucous membranes. Most of the histological abnormalities in the skin tissue include endothelial cell necrosis, localized hemorrhage, swelling, and variable degrees of cutaneous edoema. Using immunohistochemical stains, it is possible to identify various antigens in epidermal dendritic cells, endothelial cells, and connective tissue fibroblasts. The sebaceous and sweat gland epithelium also contains these antigens. Viral inclusions and particles can be observed inside endothelial cells and connective tissue using electron microscopy. Furthermore, it has been shown that the structural protein VP40 of the MV successfully aids in evading the host immune reaction to IFN (Martines et al., 2015).

To prevent the disease’s spread, the WHO has prescribed several measures to manage the virus (Mittler et al., 2018). When caring for patients with suspected or confirmed Marburg virus infections, healthcare professionals should take extra precautions to prevent infection. This means avoiding contaminated things and surfaces including soiled bedding and clothing in addition to the patient’s blood and bodily fluids. When near patients with MVD (within 1 m), healthcare staff should wear gloves, a clean, non-sterile long sleeve gown, and facial protection (a face shield or a medical mask and goggles). Residents of the affected areas should endeavor to educate the public about the signs and symptoms of the virus and the precautions that must be taken to prevent a pandemic. Healthcare professionals should think about building isolation units to immediately segregate MV-infected patients and stop person-to-person transmission (Brauburger et al., 2012). With the creation of accurate test diagnoses for suspected instances, the concept of halting transmission will also be strengthened even more. Contrary to previous epidemics, the deployment of barrier nursing techniques and training of hospital staff have benefited the general populace and decreased the incidence of nosocomial infections. Safe burial practices, sanitation standards, and public awareness campaigns are necessary to keep the virus under control since, as previously mentioned, close contact with the remains of infected people also contributes to the transmission of infection (Brauburger et al., 2012). Additionally, it is important to avoid direct contact with bodily fluids like blood, saliva, vomit, urine, and other bodily fluids from infected people. Additionally, care must be taken when handling vegetative items, such as infected needles and pins. It is also advisable to stay away from prospective carriers who are still alive and those who have passed away (such as monkeys, chimps, gorillas, fruit bats, and pigs; Government of Canada, 2023). Additionally, it is imperative that visitors to fruit bat colonies’ mines and caves wear gloves and other protective gear, including masks. The WHO further advises male MV disease survivors to practice safe sex and hygiene for 12 months from the onset of symptoms or until their semen has tested negative for MV twice (WHO, 2021a). Infection combat for Viral Hemorrhagic Fevers in the African Health Care Setting is a set of useful, hospital-based guidelines that the CDC and WHO have created in order to combat this deadly infection. Using locally accessible materials and minimal resources, this guideline intends to assist healthcare facilities in identifying cases and preventing the transmission of nosocomial diseases (CDC, 2023b). The European Network for Infectious Diseases (EUNID) outlines strategies for containing group 3 and 4 pathogen infections. Handling highly infectious diseases (HID) like MV requires cautious procedures in labs and hospitals. EUNID recommends initiating treatment for MV cases in high-level isolation units (HLIU), emphasizing isolation and cautious management. It advocates constructing specialized HLIUs for HID patients. Emergency departments must follow protocols for suspected MV cases. Laboratory personnel should inactivate samples, perform bedside tests, and adhere to safety measures. Intensive care for MV patients demands extra precautions and well-supported negative-pressure breathing apparatus. Careful management, including mask treatments and intubation, is crucial. Children with MV require careful handling to prevent spread. EUNID also offers guidelines for investigational interventions, emphasizing patient bedside procedures to minimize transmission risks (Brouqui et al., 2009).

The illness is caused by a virus that has no known cure and can only be passed from person to person or animal to animal through direct contact. Getting vaccinated is the greatest way to prevent the Marburg virus from spreading. Unfortunately, there is no Marburg virus vaccine available for use in the prevention of infection currently. Despite this, researchers have been working hard to create a vaccine for the Marburg virus, and several potential strategies have been assessed. Vaccination strategies, including the use of inactivated or destroyed Marburg virus particles, have been studied and assessed (Hunegnaw et al., 2021; Cross et al., 2022). This approach involves growing the virus in a petri dish and then killing it with heat or chemicals. The inactivated viral particles are then employed to create a vaccine. Vaccines against numerous viruses, including polio and hepatitis A, have been successfully developed using this method. One approach that has been studied is the use of a live-attenuated strain of the Marburg virus as a vaccine. This method involves making the virus less infectious or virulent by laboratory manipulation. After then, the engineered virus is used to make a vaccine. Measles and mumps can be prevented by the use of vaccines that include reduced forms of the infectious agent. The third sort of vaccination strategy that has been researched is the use of vaccines that are based on viral vectors. The core of this method is to deliver genetic material from the Marburg virus into the body via a non-pathogenic virus. An immune response will be triggered by the presence of the genetic material, protecting the body from the Marburg virus (Matassov et al., 2018; Cross et al., 2020). Infectious diseases like Ebola can be prevented and treated by vaccines that use viruses as “vectors.” A fourth method that has been tried and tested is the use of protein-based vaccines. The purpose of this method, which involves the use of a protein isolated from the Marburg virus, is to provoke an immune response. Vaccines frequently include the protein, which has been created using recombinant DNA technology. Protein-based vaccines have proven to be effective, leading to the development of preventative measures against diseases like human papillomavirus (HPV). Vaccines against Marburg virus are currently in development, although there are other choices. Possible vaccine targets include the use of vesicular stomatitis virus (VSV) as a vector, the VSV-EBOV-MV vaccine is a viral vector-based vaccination that protects against both Ebola and Marburg (Woolsey et al., 2022). The vaccine is currently being tested in clinical settings after displaying encouraging outcomes in preclinical research. The Ad26.ZEBOV/MV vaccine delivers antigens against the Ebola and Marburg viruses using an adenovirus as a vector. The NIH oversees developing this vaccine. After showing promising results in preclinical tests, the vaccine is currently being studied in clinical settings. The vesicular stomatitis virus (VSV) serves as a vector to transmit genetic material from the Ebola and Marburg viruses for the rVSVG-ZEBOV-GP/MV-GP viral vector-based immunization. Researchers from the University of Maryland created this vaccination. The vaccine is currently being tested in clinical settings after displaying encouraging outcomes in preclinical studies. A Marburg virus vaccine known as mRNA-1,360 creates an antiviral protein using mRNA technology. The vaccine is currently being tested in clinical settings after displaying encouraging outcomes in preclinical studies. The Marburg Vax vaccine is a dead virus-based immunization since it is made from inactivated Marburg virus particles. Its main goal is to provide protection (Jones et al., 2005; Marzi et al., 2019, 2021). The vaccine is currently being tested in clinical settings after displaying encouraging outcomes in preclinical studies. The creation of a Marburg virus vaccine is essential for stopping future epidemics. Although there are many ways to make vaccines, the relevant authorities have not yet approved any treatments or vaccines for MV. Prior to the 2013–2016 EBOV pandemic, there was a paucity of significant public sector investment for the development of pharmaceutical countermeasures, despite the catastrophic effects of filovirus infections on public health. However, funding for basic and translational studies of filoviruses has increased since 2016 as a result of biodefense and research grants. As a result, the licensing procedure for EBOV vaccines and medications to be used in suppressing outbreaks has advanced. With the help of this financing, MV was able to expand its study of animal models and preventative measures, both of which are essential before the start of clinical testing. In NHP research, several approaches have showed promise, and these approaches are now being developed via Phase I clinical trials for the clinical development of vaccines and antivirals (Marzi et al., 2015; Krause et al., 2020). Since almost the moment the virus was identified, a MV vaccine has been under development, but results have been patchy. Only a few of the prospective MV vaccination platforms have shown protective efficacy in NHPs, despite being extensively tested in rodent models. The MV glycoprotein (GP) is used by all presently available successful vaccine candidates as their primary antigen. It offers defense against a variety of RAVV and MV strains. As MV vaccines, fast-acting, live-attenuated, non-replicating, and replicating viral vector regimens may be utilized in multidose, single-dose, and other forms. In the event of an outbreak, reactive vaccination campaigns would make use of single-dose, quick-acting vaccinations. There are, however, a number of candidate vaccines that could be employed for at-risk groups’ regular vaccination. The duration of the acquired immunity created by the vaccine will determine whether additional immunizations are required (Dean et al., 2020; WHO, 2023c).

Two antiviral agents, T-705 (favipiravir) and remdesivir, have exhibited efficacy against Marburg virus disease (MVD) through preclinical investigations. These agents function as RNA polymerase inhibitors, impeding viral replication and transcription processes (Furuta et al., 2013; Bixler et al., 2018; Marlin et al., 2022). T-705 (favipiravir), a pyrazinecarboxamide derivative, boasts comprehensive antiviral activity across diverse viruses and holds clinical approval in Japan for addressing influenza (Zhu et al., 2018; Zadeh et al., 2022). A research study disseminated by the National Center for Biotechnology Information (NCBI) proposes T-705 as a viable therapeutic candidate against Marburg virus, particularly valuable for outbreak scenarios due to its prompt and secure oral administration following exposure (Zhu et al., 2018; Zadeh et al., 2022). Angola, a mouse-adapted Marburg virus strain, was used to infect mice in a different investigation, and T-705 showed excellent survivability in these mice (Zhu et al., 2018; Zadeh et al., 2022). Oral dosing that began 1 or 2 days after infection and continued for 8 days resulted in full mouse survival. Remdesivir functions as a monophosphoramidate nucleoside prodrug, which undergoes intracellular metabolic alteration into an active nucleoside triphosphate form, thereby inhibiting viral RNA polymerase (Malin et al., 2020). Notably, a study revealed the curative effectiveness of remdesivir in nonhuman monkeys infected with the Marburg virus experimentally, particularly when therapy started 5 days after inoculation (Porter et al., 2020). Remdesivir was demonstrated to be effective against a variety of RNA viruses in vitro and using macaque models, including the Ebola virus, Lassa virus, and Marburg virus (Malin et al., 2020). This research was published in Clinical Microbiology Reviews. It is imperative to acknowledge that the efficacy and safety of these agents in human MVD cases remain untested. Moreover, the application of antiviral drugs necessitates integration with supplementary control measures, including case isolation, surveillance, contact tracing, laboratory services, secure burials, and community mobilization, to ensure the effective management of MVD outbreaks (Cross et al., 2018; Zhu et al., 2018). T-705, also known as Favipiravir, has demonstrated effectiveness in vitro and in vivo against Marburg virus infection (Zhu et al., 2018). Mice that had been intraperitoneally infected with Marburg virus that had been modified for mice completely survived when given T-705 beginning 1 or 2 days after infection and continuing for 8 days (Zhu et al., 2018). Vero E6 cells showed no negative effects (Zhu et al., 2018). A broad-spectrum antiviral drug called Remdesivir has previously shown antiviral effectiveness against filoviruses including the Marburg virus (Levien and Baker, 2021). Respiratory failure and organ malfunction, including low albumin, low potassium, low red blood cell count, low platelet count, which aids clots, and yellow skin coloring, are the most frequent side events in Remdesivir trials for COVID-19 (Zadeh et al., 2021). Pyrexia, sleeplessness, multi-organ malfunction, DVT, and hypersensitivity/anaphylactic reactions connected to the infusion are additional negative consequences (Levien and Baker, 2021). A combination therapy of monoclonal antibodies (mAbs) and remdesivir has been shown to induce an 80% protection rate against Marburg virus in rhesus macaques (Cross et al., 2021; Rees, n.d.). The combination therapy was initiated 5 days post-inoculation with Marburg virus (Cross et al., 2021). High temperature, severe headaches, severe malaise, muscle aches and pains, gastrointestinal problems, migraines, and dizziness are all signs of Marburg virus sickness (Kortepeter et al., 2020; WHO, 2021b,c). Marburg virus sickness has a case fatality ratio that can reach 88%, but it can be significantly reduced with proper patient care (WHO, 2021b). In summary, Remdesivir has shown antiviral activity against filoviruses like Marburg virus, whereas T-705 has showed efficacy against Marburg virus infection in vitro and in vivo. In rhesus macaques, monoclonal antibody and remdesivir combination therapy has been reported to result in an 80% protection rate against Marburg virus. High temperature, severe headaches, severe malaise, muscle aches and pains, gastrointestinal problems, migraines, and disorientation are all signs of Marburg virus sickness.

Clinical trials have been conducted for some drugs to treat MV; some of these trials have been completed and others are ongoing. MV drug development has progressed much more slowly than preclinical and clinical trials for the treatment of EBOV. Antiviral effectiveness against MV infections in nonhuman primates (NHPs) has long been regarded as the gold standard to assess prospective efficacy in humans and support subsequent clinical trials, much like EBOV. Following exposure in NHPs with advanced disease, several promising strategies, such as pan-filoviral small-molecule antivirals and MV-specific monoclonal antibodies, have shown excellent success. Table 5 shows the biologics currently being tested in clinical trials, along with their current status and research center location (Citeline Clinical, 2023).

The emergence of Marburg virus (MV) has presented a complex global challenge characterized by fatal outbreaks and significant clinical hurdles. The extensive analysis conducted in this study sheds light on the multifaceted nature of MV, encompassing its origin, transmission dynamics, clinical manifestations, and the intricate interplay between the virus and its human hosts. The documented outbreaks underscore the urgency of understanding and effectively addressing the threat posed by MV to global health security. Throughout this investigation, it has become evident that the clinical challenges posed by MV are substantial, with its virulent nature leading to high mortality rates and a range of severe symptoms. The lack of specific antiviral therapies or vaccines further amplifies the urgency of comprehensive prevention and control strategies. The cases studied emphasize the need for rapid, coordinated responses involving healthcare providers, researchers, and governmental bodies to curtail the impact of MV outbreaks. The global perspective on MV’s emergence emphasizes the need for proactive, multidisciplinary approaches to prevent and mitigate its devastating impact. The lessons learned from past outbreaks underscore the importance of preparedness, collaboration, and innovation in addressing this ongoing threat to public health. Through these concerted efforts, we can hope to avert future MV outbreaks and minimize their toll on human lives.

Looking ahead, several crucial research and intervention directions emerge from our analysis. First, continued efforts are imperative to elucidate the intricate mechanisms of MV transmission from its reservoir hosts to humans, allowing for the identification of potential intervention points. Collaborative studies integrating virology, epidemiology, and ecology will be pivotal in achieving a comprehensive understanding of the virus’s life cycle. Second, the development of effective preventative measures remains paramount. Advances in vaccine technologies offer promise for the creation of MV-specific vaccines, analogous to strategies employed against related pathogens. In parallel, research should focus on identifying small molecule antiviral compounds that can impede MV replication and spread. Third, bolstering healthcare infrastructure in regions susceptible to MV outbreaks is essential. Strengthening diagnostic capabilities, training healthcare workers in effective infection control measures, and establishing rapid response protocols are vital components of managing MV cases and preventing wider disseminations.

SSr, DS, SK, and AS: concept and original draft. RR, AA, SA, SR, SSa, ZA-q, PB, AM, AR-M, and RS: reviewing and editing. RS: supervision. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.