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Signal Transduction and Targeted Therapy Dec 2023In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and... (Review)
Review
In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.
Topics: Humans; Artificial Intelligence; Mpox (monkeypox); Antibodies; Disease Outbreaks; Antiviral Agents
PubMed: 38148355
DOI: 10.1038/s41392-023-01675-2 -
Nature Microbiology Nov 2023Mpox virus (MPXV) primarily infects human skin to cause lesions. Currently, robust models that recapitulate skin infection by MPXV are lacking. Here we demonstrate that...
Mpox virus (MPXV) primarily infects human skin to cause lesions. Currently, robust models that recapitulate skin infection by MPXV are lacking. Here we demonstrate that human induced pluripotent stem cell-derived skin organoids are susceptible to MPXV infection and support infectious virus production. Keratinocytes, the predominant cell type of the skin epithelium, effectively support MPXV infection. Using transmission electron microscopy, we visualized the four stages of intracellular virus particle assembly: crescent formation, immature virions, mature virions and wrapped virions. Transcriptional analysis showed that MPXV infection rewires the host transcriptome and triggers abundant expression of viral transcripts. Early treatment with the antiviral drug tecovirimat effectively inhibits infectious virus production and prevents host transcriptome rewiring. Delayed treatment with tecovirimat also inhibits infectious MPXV particle production, albeit to a lesser extent. This study establishes human skin organoids as a robust experimental model for studying MPXV infection, mapping virus-host interactions and testing therapeutics.
Topics: Humans; Mpox (monkeypox); Monkeypox virus; Induced Pluripotent Stem Cells; Organoids
PubMed: 37828248
DOI: 10.1038/s41564-023-01489-6 -
Advances in Experimental Medicine and... 2024The family Poxviridae is a large family of viruses with a ubiquitous distribution, subdivided into two subfamilies: Chordopoxvirinae (poxviruses of vertebrates) and... (Review)
Review
The family Poxviridae is a large family of viruses with a ubiquitous distribution, subdivided into two subfamilies: Chordopoxvirinae (poxviruses of vertebrates) and Entomopoxvirinae (poxviruses of insects). Only three species from the first subfamily, Orthopoxvirus (OPV), Molluscipoxvirus and Parapoxvirus, can infect the human being. In the paediatric population, viruses belonging to the first two subfamilies have the greatest importance. Following the eradication of smallpox in 1980, vaccination of the general population was discontinued after careful consideration of the risks and benefits. However, nearly all children and most of the world's population had little to no protection against OPV. The aim of this chapter is to review the current evidence on the aetiology, clinical manifestations, diagnosis and management of Poxviridae infections in children.
Topics: Humans; Child; Poxviridae Infections; Poxviridae; Child, Preschool; Infant; Animals
PubMed: 38801580
DOI: 10.1007/978-3-031-57165-7_13 -
Pediatric Emergency Care Nov 2023Human mpox (formerly known as monkeypox) is a zoonotic disease that causes a smallpox-like infection in humans. The mpox virus, the causative agent of mpox, was first...
Human mpox (formerly known as monkeypox) is a zoonotic disease that causes a smallpox-like infection in humans. The mpox virus, the causative agent of mpox, was first reported to cause human disease in a 9-month-old infant in the Democratic Republic of the Congo in 1970. Since that time, periodic outbreaks in primarily endemic regions have occurred, typically secondary to transmission from wildlife reservoirs. However, in May 2022, after a rapid rise in worldwide cases in largely nonendemic countries, the World Health Organization declared mpox a Public Health Emergency of International Concern. As of January 2022, more than 80,000 cases of mpox in nonendemic countries have occurred, and more than 25,000 cases in the United States alone. Most of these cases occurred in adults, with the highest frequency among men who had sex with men. Children and adolescents represented only 0.3% of US cases as of September 2022, with most infections in young children the result of direct contact with an infected household member. Although infection remains uncommon in US children and teens, pediatric emergency and urgent care providers should be aware of the clinical features, treatment, and prophylaxis of this important emerging infectious disease.
Topics: Adolescent; Adult; Infant; Male; Humans; Child; Child, Preschool; Mpox (monkeypox); Awareness; Disease Outbreaks
PubMed: 37902655
DOI: 10.1097/PEC.0000000000003063 -
Ocular Immunology and Inflammation Apr 2024
Topics: Animals; Humans; Mpox (monkeypox); Zoonoses; Disease Outbreaks
PubMed: 38527231
DOI: 10.1080/09273948.2023.2298177 -
Pediatric Emergency Care Nov 2023
Topics: Humans; Mpox (monkeypox)
PubMed: 37902656
DOI: 10.1097/01.pec.0000995496.96949.81 -
The New England Journal of Medicine Sep 2023
Topics: Humans; Mpox (monkeypox)
PubMed: 37672692
DOI: 10.1056/NEJMp2212931 -
Advances in Experimental Medicine and... 2024Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral... (Review)
Review
Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.
Topics: Humans; Animals; Poxviridae Infections; Antiviral Agents; Pneumonia, Viral; Poxviridae; Vaccinia virus; Smallpox; Variola virus
PubMed: 38801579
DOI: 10.1007/978-3-031-57165-7_12 -
Advances in Experimental Medicine and... 2024The complex cytoplasmic DNA virus known as the fowlpox virus (FWPV) is a member of the avipoxvirus genus, Subfamily Chordopoxvirinae, and Family Poxviridae. The large... (Review)
Review
The complex cytoplasmic DNA virus known as the fowlpox virus (FWPV) is a member of the avipoxvirus genus, Subfamily Chordopoxvirinae, and Family Poxviridae. The large genome size of FWPV makes it a potential vector for the creation of vaccines against a range of serious veterinary and human ailments. It also allows for multiple gene insertion and the generation of abortive infection in mammalian cells. The virus, which causes fowlpox in chickens and turkeys, is mainly transmitted to poultry through aerosols or biting insects. Fowlpox is a highly contagious disease that affects both domestic and wild birds, causing cutaneous and/or diphtheritic illnesses. To control the illness, strict hygiene practices and immunization with FWPV attenuated strains or antigenically similar pigeon pox virus vaccines are employed. Recent years have seen an increase in fowlpox outbreaks in chicken flocks, primarily due to the introduction of novel forms of FWPV. It is believed that the pathogenic characteristics of these strains are enhanced by the integration of reticuloendotheliosis virus sequences of variable lengths into the FWPV genome. The standard laboratory diagnosis of FPV involves histopathological analysis, electron microscopy, virus isolation on chorioallantoic membrane (CAM) of embryonated chicken eggs or cell cultures, and serologic techniques. For quick and consistent diagnosis, polymerase chain reaction (PCR) has proven to be the most sensitive method. PCR is used in concert with restriction endonuclease enzyme analysis (REA) to identify, differentiate, and characterize the molecular makeup of isolates of the fowlpox virus. Sequencing of the amplified fragments is then done.
Topics: Fowlpox virus; Animals; Fowlpox; Chickens; Genome, Viral
PubMed: 38801571
DOI: 10.1007/978-3-031-57165-7_4 -
Cell Mar 2024In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly...
In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust TÂ cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).
Topics: Animals; Humans; Mice; Macaca fascicularis; Monkeypox virus; Mpox (monkeypox); Smallpox Vaccine; Vaccines, Combined; Vaccinia virus
PubMed: 38366591
DOI: 10.1016/j.cell.2024.01.017