Modified coptisine derivatives as an inhibitor against pathogenic Rhizomucor miehei, Mycolicibacterium smegmatis (Black Fungus), Monkeypox, and Marburg virus by molecular docking and molecular dynamics simulation-based drug design approach.

During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our in silico investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg viruses.

Lassa Fever. Part 2. Laboratory Diagnostics, Treatment, Development of Medications

Globalization and high-speed means of transportation contribute to the spread of infections dangerous to humans. Airborne pathogens have pandemic potential as currently shown in case of the novel coronavirus SARS-CoV-2. Natural focal Lassa fever (LF) common in West African countries, in 35 cases was registered in non-endemic geographical areas because any person infected with Lassa virus (LASV) is a long-term source of infection (up to two months). Cases of person-to-person infection in endemic territories are described. In Germany, the facts of secondary virus transmission from patients to doctors have been recorded during the examination and blood collection from an apparently healthy person as well as during the autopsy of a deceased subjects due to severe LF course. Nonspecific malaise symptoms in LF are also characteristic of numerous other diseases common on the African continent, e.g., malaria and typhoid fever or viral infections such as yellow fever, Chikungunya, dengue and Zika, monkey pox and Ebola virus disease. In this regard, there may be similar dermatological manifestations. Timely detection of cases and differential diagnosis are crucial to ensure safe patient care and use of affordable antiviral therapy for LL provided by the drug Ribavirin. Research methods for studying LASV use polymerase chain reaction (PCR) for detecting viral RNA, electron microscopy, isolation of infectious virus cultured sensitive cells, indirect immunofluorescence reaction, enzyme immunoassay (ELISA) and immuno-chromatographic assays for the detection of antibodies and/or antigen as well as immunoblotting. Currently, test kits based on molecular and genetic methods are mainly used for LF laboratory diagnostics. Since the 1980s, ribavirin has been used to treat patients with LF. The serum accumulation of the drug in large quantities causes hemolysis, development of anemia and impaired renal function. In this regard, treatment options are being considered with decline in its concentration due to combined use with other antiviral drugs. A search for new therapeutic agents capable of inhibiting viral replication at disease early stage has been in progress due to lack of any approved vaccines.

An unusually fulminant case of encephalomyelitis in an 80 year old

Background: There have been reports of demyelinating syndromes in association with COVID-19 and to a much lesser extent COVID 19 vaccines. The association between demyelination and vaccines, in general, remains controversial. We review a presentation of fulminant demyelination, and discuss antecedent COVID-19 vaccination, the formulation of a broader differential diagnosis and ultimately the pathologic diagnosis. Case presentation: An 80-year-old woman presented with seizure, encephalopathy, quadriparesis and ultimately expired. She received a SARS-CoV-2 vaccine one day prior. Imaging revealed contrast enhancing cerebral lesions, longitudinally extensive transverse myelitis. CSF was markedly inflammatory. Pathologic examination of the CNS lesions revealed demyelination and inflammation beyond white matter, not restricted to a perivenular distribution. Conclusion(s): This case depicts a seemingly fulminant course of a diffuse demyelinating syndrome characterized clinicopathologically as Marburg's variant of multiple sclerosis. There are several unique aspects of this case including the extremely rapid course, the unusual evolution of CSF abnormalities, with hypoglycorrhachia and markedly elevated protein. The proximity to vaccination is a pertinent association to document, though we cannot unequivocally prove causation.Copyright © 2022 The Authors

Enhancing vaccination of key populations: lessons and actions

Vaccination is effective in preventing the increase of disease, especially emerging infectious diseases (EIDs), and it is particularly important for people in close contact with infected sources and susceptible populations who are at increased risk of getting infectious diseases due to behavior, occupation or health. Despite targeted vaccination guidelines, inadequate vaccination of the key populations fails to receive widespread attention, resulting in a high-risk transition of disease from key populations to general populations. Strengthening the vaccination of the susceptible groups can effectively block the spread of pathogens to general populations, and reduce the consumption of medical resources in universal vaccination, which has significant economic value. In this review, we describe the prevalence of EIDs, analyze the experience and lessons of infectious disease vaccination in key populations through several cases, and further explore the causes for the decline in vaccination rates of key populations. According to the trends of EIDs, a plan to strengthen the vaccination of key populations is proposed to effectively prevent the transition of EIDs from key populations to general populations.

Approaches to demonstrating the effectiveness of filovirus vaccines: Lessons from Ebola and COVID-19.

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.

Marburg Virus- A threat during SARS-CoV-2 era: A Review.

In the German towns of Marburg, Frankfurt, and Belgrade in 1967, this single negative-stranded RNA virus was initially discovered. The importation of infected grivet monkeys from Uganda is what caused this virus-related sickness. As a result of the early link between viruses and non-human primates, this virus is frequently referred to as vervet monkey sickness. This virus causes Marburg hemorrhagic fever in humans and non-human primates. Human endothelial cells serve as the primary vehicle for replication. According to a 2009 report, the virus was being stored in Egyptian fruit bats (Rousettus aegyptiacus). Body fluids, unprotected sex, broken or injured skin, and other bodily fluids are the main routes of transmission. After the incubation period, symptoms like chills, headaches, myalgia, and stomach pain start to show up. There is no specific medication for such an infection, only hydration therapy and adequate oxygenation are followed. The following diagnostic techniques can be used to confirm the diagnosis: (i) an antibody-capture enzyme linked immunosorbent assay (ELISA); ii) an antigen capture ELISA test; iii) a serum neutralization test; iv) an RT PCR assay; v) electron microscopy; or vi) virus isolation by cell culture. Because MARV is a risk group 4 infection, laboratory staff must take strict precautions (RG-4).

Production and characterization of lentivirus vector-based SARS-CoV-2 pseudoviruses with dual reporters: Evaluation of anti-SARS-CoV-2 viral effect of Korean red ginseng.

Background: Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean red ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus. Methods: A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2. Results: The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect. Conclusion: The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.

Marburg virus disease: the paradox of Nigeria's preparedness and priority effects in co-epidemics.

Background: The recent outbreaks of Marburg virus disease (MVD) in Guinea and Ghana have become a major public health concern not only to the West African sub-region but a threat to global health. Main body of the abstract: Given the poorly elucidated ecological and epidemiological dynamics of the Marburg virus, it would be imprudent to preclude the possibility of another pandemic if urgent efforts are not put in place. However, the prior emergence and impact of COVID-19 and other co-occurring epidemics may add 'noise' to the epidemiological dynamics and public health interventions that may be required in the advent of a MVD outbreak in Nigeria. Short conclusion: Paying attention to the lessons learned from previous (and current) multiple epidemics including Avian Influenza, Yellow fever, Ebola virus disease, Monkeypox, Lassa fever, and COVID-19 could help avoid a potentially devastating public health catastrophe in Nigeria.

Recent outbreak of Marburg virus disease: Could it be a threat for global public health?

3 It has been linked to several outbreaks since its simultaneous identification and characterization in 1967 in Marburg and Frankfurt, Germany, as well as in Belgrade, Serbia. 4 A few documented cases of MVD have been reported in Africa from 1975 to 1985. [...]1998, MVD was not considered as fatal as the Ebola virus. Hemorrhagic fever syndromes though a crucial disease indication. Because they resembled more widespread illnesses like malaria and typhoid, early instances may be overlooked. There is currently no recognized vaccine or antiviral medication for treating MVD. 1 A few documented cases of MVD have been reported in Africa are undergoing Phase I, II, and III clinical studies. 12 A standardized literature review reported that antiviral drugs such as Galidesivir, Favipiravir, and Remdesivir showed promising results with an 83% to 100% success rate when the drugs are given at a specific dosage regimen. 2 Though their efficacy is not fully proven against a large population, their usage is not yet approved by the Food and Drug Administration (FDA) or any other authorized organization. 2 In brief, when the Marburg virus comes into human contact, it only takes a few days to cause a deathly situation, and effective treatment is not available yet. [...]it is more important to consider the outbreak of MVD as an alarming situation. There are some common overlapping symptoms of these three viral infections. [...]the global health-care authorities should develop and adopt differential diagnostic techniques for quick detection and isolation of cases.

FIFA World Cup 2022 and the Risk of emergence of Zoonotic Diseases

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. [ FROM AUTHOR]

A review of treating viral outbreaks with self-assembled nanomaterial-like peptides: From Ebola to the Marburg virus

Cases of the Marburg virus have started to rise and there is an urgent need to find a cure or therapy before another world-wide quarantine is introduced. There are no treatments for this virus other than giving infected people plenty of water due to excessive bleeding. Here, we report a growing strategy to use self-assembled nano peptides to attach to and inhibit viruses from replicating. Specifically, we summarize the research of others who have used this approach for Ebola, SARS-CoV-2, and other viruses and even provide our own eight octapeptides that show interference with the Marburg virus and viral RNA. These peptides self-assemble in a similar matter as the virus itself self-assembling along the viral RNA. These eight octapeptides (KLVVGDRAS, GDRASIEK, EILLAREL, ARELTLRK, FLSFCSLF, CSLFLPKL, WITWMTIW, and MTIWIPEI) were selected based on a conserved nanoparticle core sequence containing both N- and C- terminal lobes. The total atomic contact energy of these peptides as determined through computational modeling are: -110.97501, -118.57263, -99.82477, -120.60967, -17.14494, -52.11275, -14.02828, and -45.64357 kcal/mol, respectively. Collectively with results from other researchers who have designed self-assembled nano peptides to passivate other viruses, this report summarizes the strong attraction that can occur between candidate peptides to the Marburg virus. Further in vitro and in vivo studies of these peptides are needed to fully evaluate their efficacy to treat the Marburg virus, but clearly this review article demonstrates that there is a strong future for using self-assembled nano peptides to prevent and treat viral outbreaks.

Bat and bat-borne hantaviruses

Hantaviruses are important pathogenes of natural focal diseases that causes hemorrhagic fever with renal syndrome and Hantavirus pulmonary syndrome. According to the latest classification of the International Committee on Taxonomy of Viruses, hantaviruses can be divided into 53 species, 7 genera, and 4 subfamilies. Hantaviruses are widely found in Rodentia, Chiroptera, and Insectivora, and later also found in reptile, Actinopterygii, and Agnatha. There are many species of bats, which are the second largest group of mammals in the world after rodents. At present, 1 446 species have been reported, accounting for about 22% of global mammals. In addition, bats have strong flight ability and are widely distributed in all continents except Antarctica. As the host animal of viruses, bats bear a variety of viruses, and many emerging infectious pathogens such as Marburg virus, Hendra virus, and Nipah virus have been confirmed to come from bats. Bats have also been associated to Ebola virus, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2. In recent decades, more and more bat-borne hantaviruses have been discovered. Bats and bat-borne hantaviruses have an important research value. Therefore, this paper reviews the latest classification of Hantavirus and bat-borne hantaviruses.

miR-142 Targets TIM-1 in Human Endothelial Cells: Potential Implications for Stroke, COVID-19, Zika, Ebola, Dengue, and Other Viral Infections.

T-cell immunoglobulin and mucin domain 1 (TIM-1) has been recently identified as one of the factors involved in the internalization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells, in addition to angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), neuropilin-1, and others. We hypothesized that specific microRNAs could target TIM-1, with potential implications for the management of patients suffering from coronavirus disease 2019 (COVID-19). By combining bioinformatic analyses and functional assays, we identified miR-142 as a specific regulator of TIM-1 transcription. Since TIM-1 has been implicated in the regulation of endothelial function at the level of the blood-brain barrier (BBB) and its levels have been shown to be associated with stroke and cerebral ischemia-reperfusion injury, we validated miR-142 as a functional modulator of TIM-1 in human brain microvascular endothelial cells (hBMECs). Taken together, our results indicate that miR-142 targets TIM-1, representing a novel strategy against cerebrovascular disorders, as well as systemic complications of SARS-CoV-2 and other viral infections.

Synthesis and Antiviral Properties of Camphor-Derived Iminothiazolidine-4-Ones and 2,3-Dihydrothiazoles.

A set of heterocyclic products was synthesized from natural (+)-camphor and semi-synthetic (-)-camphor. Then, 2-Imino-4-thiazolidinones and 2,3-dihydrothiazoles were obtained using a three-step procedure. For the synthesized compounds, their antiviral activity against the vaccinia virus and Marburg virus was studied. New promising agents active against both viruses were found among the tested compounds.

Marburg virus outbreak in Ghana: An impending crisis.

Since the initial identification of the Marburg virus in 1967, it has sporadically emerged in several countries throughout Africa, including Zimbabwe, Kenya, South Africa, the Democratic Republic of the Congo (DRC), Uganda, and Zimbabwe. Due to the concurrent occurrence of other epidemics like the coronavirus disease 2019 (COVID-19), this outbreak could endanger the healthcare systems in these many African nations. Recently, two cases of the Marburg virus were detected in Ghana for the first time. However, there has been a noticeable lack of information concerning this recent outbreak of July 2022 in Ghana. Therefore, this article seeks to provide an overview of this outbreak in Ghana to better understand the most recent status and current efforts being made to mitigate the dissemination of the Marburg virus. We also suggest recommendations that may contribute to limiting the burden of this virus.

Marburg virus disease: A deadly rare virus is coming.

Two cases of the deadly Marburgvirus were reported in Ghana, which might be a new global virus alert following COVID-19 and novel monkeypox. Thus far, there is no vaccine or treatment for Marburg virus disease, which is a disease with a mortality rate as high as that of Ebola. Although now human infections with Marburgvirus occurred mainly in Africa, outbreaks were twice reported in Europe over the past 55 years. A concern is that globalization might promote its global viral transmission, just like what happened with COVID-19. The current study has briefly summarized the etiology, epidemiology, and clinical symptoms of the Marburgvirus as well as vaccine development and experimental treatments in order to prevent and control this virus.

A platform trial design for preventive vaccines against Marburg virus and other emerging infectious disease threats.

BACKGROUND: The threat of a possible Marburg virus disease outbreak in Central and Western Africa is growing. While no Marburg virus vaccines are currently available for use, several candidates are in the pipeline. Building on knowledge and experiences in the designs of vaccine efficacy trials against other pathogens, including SARS-CoV-2, we develop designs of randomized Phase 3 vaccine efficacy trials for Marburg virus vaccines. METHODS: A core protocol approach will be used, allowing multiple vaccine candidates to be tested against controls. The primary objective of the trial will be to evaluate the effect of each vaccine on the rate of virologically confirmed Marburg virus disease, although Marburg infection assessed via seroconversion could be the primary objective in some cases. The overall trial design will be a mixture of individually and cluster-randomized designs, with individual randomization done whenever possible. Clusters will consist of either contacts and contacts of contacts of index cases, that is, ring vaccination, or other transmission units. RESULTS: The primary efficacy endpoint will be analysed as a time-to-event outcome. A vaccine will be considered successful if its estimated efficacy is greater than 50% and has sufficient precision to rule out that true efficacy is less than 30%. This will require approximately 150 total endpoints, that is, cases of confirmed Marburg virus disease, per vaccine/comparator combination. Interim analyses will be conducted after 50 and after 100 events. Statistical analysis of the trial will be blended across the different types of designs. Under the assumption of a 6-month attack rate of 1% of the participants in the placebo arm for both the individually and cluster-randomized populations, the most likely sample size is about 20,000 participants per arm. CONCLUSION: This event-driven design takes into the account the potentially sporadic spread of Marburg virus. The proposed trial design may be applicable for other pathogens against which effective vaccines are not yet available.

FUTURE PANDEMICS: AGENTS, POTENTIAL AND IMPACTS

The ongoing COVID-19 pandemic has changed the dimensions of human life. This new novel coronavirus has taken the world through a plethora of challenges affecting the health, economy, social and global security. As of 25 May 2021, with the death of 34, 72, 068 people and 167, 011, 807 affected, it’s high time to focus on measures to save future generations. The covid vaccination drive has started and the WHO approved vaccines are Oxford-AstraZeneca, Pfizer-BioNTech, Sinopharm-BBIBP, Moderna, and Johnson & Johnson. Dated 23 May 2021, a total of 1, 489, 727, 128 vaccine doses have been administered worldwide. WHO Director-General Tedros Adhanom Ghebreyesus has put forward the concept of an integrated One Health approach to public health, animal health and the environment, during the opening of the 27thTripartite Annual Executive Committee Meeting World Organization for Animal Health (OIE) to prevent future pandemics (17 February 2021). Four international organizations - the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), the United Nations Environment Programme (UNEP) and the World Health Organization (WHO) will operate under One Health approach to identify the links between the health of people, animals, and the environment. This will contribute to safeguard the human race. He also warned about the possibility of the next pandemic threat - Disease X and other zoonotic diseases which could arise anytime. According to the WHO chief, the COVID-19 pandemic demonstrated “intimate” linkages between the health of humans, animals and ecosystems, as zoonotic diseases spread between animals and people. For combatting the next pandemic, the World Health Organisation (WHO) prepared a global strategy for a pandemic response, the research and development (R&D) Blueprint. This R&D Blueprint has a list of identified priority diseases and a roadmap response plan for each of them. The diseases which pose a significant public health risk because of their potential to cause pandemics, as well as the lack of sufficient countermeasures against these (diseases), includes Crimean-Congo hemorrhagic fever (CCHF), MERS, SARS, Ebola, Nipah and several other dangerous infectious diseases. In this chapter, we will discuss some priority diseases which could arise as a future pandemic. © 2022 by Nova Science Publishers, Inc.