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There is a danger that a natural smallpox virus may be reintroduced from the unknown spring or that a similar virus with the same pathogenic properties may appear or that somebody may create a synthetic copy of such a virus. That is why it is crucial to have a proper laboratory pattern that may imitate a natural smallpox disease and other human orthopoxviruses. A rabbitpox virus may provoke a grave and highly contagious disease in rabbits with a high death rate. The symptoms of this disease in rabbits is similar to symptoms of natural smallpox in humans. There have been no cases of rabbitpox in humans.Purpose of the study – To summarize data on research of a rabbitpox virus and to analyze the symptoms of this disease in rabbits that is similar to a natural pox virus in humans. This analysis may contribute to the development of new drugs against smallpox.Study base sources – English scientific papers available on the Internet.Method of the study – Analytical.Results and discussion. Rabbitpox was first detected in 1930 in lab. rabbits in Utrecht, the Netherlands, then in the USA, at Rockfeller University in New York. From 1941 the outbreaks of rabbitpox were registered in research institutes in Europe and in the USA. However, there were no cases of this disease in rabbits in the wildlife. The analysis has demonstrated that the pattern “a rabbit–a rabbitpox virus” has been quite successful in pre-clinical studies of protective efficiency of orthopoxvirus vaccines, monoclonal antibodies, mRNA-based drugs and chemotherapeutic agents (thiosemicarbazone, Cidofovir, tecovirimat, Brincidofovir, etc.) for different transmission modes including inhalative one. This pattern is also useful for evaluation of diagnostic sets, employed for orthopoxviruses detection.Conclusion. Pattern “a rabbit–a rabbitpox virus” is safe for humans and is promising for simulation of different pathological states when we conduct various medical and biological studies of orthopoxvirus infections. It also may be used to evaluate the efficiency of immunobiological drugs against smallpox, chemotherapeutic agents and diagnostic sets.

Heterologous protein expression often faces significant challenges, particularly when the target protein has posttranslational modifications, is toxic, or is prone to misfolding. These issues can result in low expression levels, aggregation, or even cell death. Such problems are exemplified by the expression of phospholipase p37, a critical target for chemotherapeutic drugs against pathogenic human orthopoxviruses, including monkeypox and smallpox viruses. The complex structure and broad enzymatic activity of phospholipase p37 render it toxic to host cells, necessitating specialized strategies for heterologous expression. In our study, we addressed these challenges using the vaccinia virus F13 protein as a model. We demonstrated that p37 can be effectively synthesized in E. coli as a GST fusion protein by co-expressing it with the GroEL/ES chaperone system and Trigger Factor chaperone. [ABSTRACT FROM AUTHOR]

The growing concern about the monkeypox (Mpox) virus infection has garnered a lot of public attention. However, the treatment options available to combat the same is limited to tecovirimat. Additionally, in a possible incidence of resistance, hypersensitivity, or adverse drug reaction, it is imperative to devise and reinforce the second-line therapy. Thus, in this editorial, the authors suggest seven antiviral drugs that could potentially be repurposed to combat the viral illness. [ABSTRACT FROM AUTHOR]

We introduce a phylogeny-aware framework for predicting linear B-cell epitope (LBCE)-containing regions within proteins. Our approach leverages evolutionary information by using a taxonomic scaffold to build models trained on hierarchically structured data. The resulting models present performance equivalent or superior to generalist methods, despite using simpler features and a fraction of the data volume required by current state-of-the-art predictors. This allows the utilization of available data for major pathogen lineages to facilitate the prediction of LBCEs for emerging infectious agents. We demonstrate the efficacy of our approach by predicting new LBCEs in the monkeypox (MPXV) and vaccinia viruses. Experimental validation of selected targets using sera from infected patients confirms the presence of LBCEs, including candidates for the differential serodiagnosis of recent MPXV infections. These results point to the use of phylogeny-aware predictors as a useful strategy to facilitate the targeted development of immunodiagnostic tools. [ABSTRACT FROM AUTHOR]

In the last 10 years, scientists' interest in the horsepox pathogen has increased sharply due to the obtaining of its chimeric copy and the discussion of whether it was used to create early smallpox vaccines and the dangers of technologies that allow the restoration of extinct pathogens of dangerous infections.The aim of the work is to summarize the materials on modern studies of the horsepox virus.The source base of the study is English-language scientific literature available via the Internet.The research method is an analysis of scientific sources on horsepox from the general to the specific. We considered the area of distribution of the virus, its epidemiological danger, phylogenetic relationship, data on the sequencing of the horsepox virus genome and the likelihood of its use in the creation of the first vaccines, as well as obtaining its chimeric copy, on the basis of which a new smallpox vaccine was created – TNX-801.Results and discussion. The horsepox virus belongs to the poxvirus family, the orthopoxvirus genus. Classical horsepox has previously been reported only in Europe (France), Mongolia, and Kenya. The complete nucleotide sequence of the horsepox virus genome MNR-76 isolated in Mongolia has been determined. In addition to genes common to all orthopoxviruses, it includes intact genes specific only to this virus, the homologues of which are fragmented in the genome of other orthopoxviruses. Phylogenetic analysis of a number of orthopoxviruses was performed and a phylogenetic tree was constructed based on the conserved central region of the genome and some of the more variable terminal regions. The data obtained indicate that horsepox virus is most closely related to vaccinia virus and rabbitpox virus strains. Although horsepox is currently considered extinct, its pathogen may persist in unknown reservoirs. The data on the sequencing of the horsepox virus genome, strain MNR-76, suggest that horsepox virus could have served as the basis for the first smallpox vaccines. A chimeric copy of the horsepox virus was obtained using synthetic biology, which was used to create a new smallpox vaccine, TNX-801. On its basis, a recombinant vaccine against SARS-CoV-2 was constructed. The restoration of "extinct viruses" using synthetic biology methods has led to intense debates about the benefits and risks of such research.Conclusion. It cannot be ruled out that the use of modern genetic engineering technologies may lead not only to the development of effective vaccines, but also to the production of new orthopoxviruses pathogenic for humans and animals, or to the reintroduction of smallpox, which is especially dangerous in the context of the virtual absence of smallpox immunity in the population and international control over experiments in the synthetic biology of dangerous pathogens.

The recently re-emerged mpox (monkeypox) virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide. Numerous studies have contributed to our understanding of its evolution, pathophysiology, and clinical manifestations. The current outbreak of the mpox virus depicts its novel route of transmission as a new variant. However, the exact reason for its transition from an epidemic to a pandemic remains unclear. Furthermore, other poxviruses such as vaccinia virus, variola virus, and cowpox virus, also belong to the same genus, Orthopoxvirus. In the present review, our objective was to summarize the evidence on evolution, pathophysiology, and clinical manifestations of mpox virus and its related poxviruses. The present review would aid in a better understanding of the current circulating mpox virus and its differences from other poxviruses. In addition, the shared genetic factors contributing to virulence in these Orthopoxvirus highlight their evolutionary connections and genetic similarities. While they exhibit differences in virulence, studying these genetic relationships is crucial for understanding their biology, pathogenicity, and the development of effective vaccines and antiviral therapeutics to curb mpox disease.

The basis for criteria of the taxonomic classification of DNA and RNA viruses based on data of the genomic sequencing are viewed in this review. The genomic sequences of viruses, which have genome represented by double-stranded DNA (orthopoxviruses as example), positive-sense single-stranded RNA (alphaviruses and flaviviruses as example), non-segmented negative-sense single-stranded RNA (filoviruses as example), segmented negative-sense single-stranded RNA (arenaviruses and phleboviruses as example) are analyzed. The levels of genetic variability that determine the assignment of compared viruses to taxa of various orders are established for each group of viruses.

Discontinuation of vaccination after the completion of Smallpox global eradication program led to a sharp decrease in the level of collective immunity not only to smallpox but also to other orthopoxvirus infections. Over the past 10–15 years, the world has seen an increase in the frequency of diseases caused by smallpox viruses of cows, buffaloes, camels. The outbreak of mpox (a disease caused by the monkey pox virus) occurred in 2022–2023. Analysis of the literature data on the organization of the orthopoxvirus genome suggest that smallpox could have occurred in the past as a result of evolutionary changes in the zoonotic progenitor virus. In this regard, there is a threat of a new particularly dangerous anthropozoonosis, the pathogen of which can occur both naturally and artificially. The aim of the review is to analyze open science published data on aerobiological research with OPVs conducted by the U.S. Department of Defense from 1994-2013, which was a period of restricted research and storage of smallpox virus samples. The authors did not find any publications of the results of aerobiological research with orthopoxviruses conducted by the US Department of Defense after 2013 in open scientific sources. The review presents a data analysis in Russian and English-speaking scientist publication as well as those posted on the Internet. The presented results of aerobiological studies with orthopoxviruses indicate the interest of the US military department in carrying out experimental work of dual use, including monitoring of the properties of orthopoxviruses and a possible change in their pathogenicity for humans, selection of optimal laboratory models for studying the properties of orthopoxviruses, and the possibility of modeling the properties of the smallpox virus when using other orthopoxviruses (cowpox virus, rabbit pox virus, monkey pox virus), modeling of the main characteristics of the disease caused by the smallpox virus in humans and evaluation of the effectiveness of existing and newly developed vaccines against smallpox, comparative study of effectiveness of antiviral drugs for regular or post-exposure prophylaxis of naturally occurring smallpox and monkey smallpox.

Background/Objectives: Monkeypox (mpox) is currently the most common orthopoxvirus (OPXV) zoonotic disease, and, since 2022, there has been atypical person-to-person transmission observed in non-endemic countries. The present study aimed to investigate the frequency of monkeypox virus (MPXV) and OPXV DNA detection in recommended and alternative clinical materials taken during the acute and convalescent phases of infection in Bulgarian patients. Methods: The study included laboratory investigation by real time PCR of 181 clinical samples from 42 Bulgarian patients with possible mpox infections. Results: MPXV DNA was detected in 23/181 (12.71%), and OPXV DNA in 20/181 (11.05%) clinical samples. There were six mpox-confirmed patients aged 23 to 44. At the highest frequency, MPXV and OPXV DNA were detected in samples of vesicular contents (6/6) and nasal/oropharyngeal secretions (5/6 and 4/6) during the first three days from the appearance of clinical symptoms. We demonstrated MPXV and OPXV DNA in alternative samples (urine, feces, ejaculate, and saliva), and in follow-up patient samples, taken two weeks after mpox confirmation in the convalescent phase (vesicular contentsand urine). Conclusions: Our findings suggested that MPXV may be detected in a larger set of clinical materials, including alternatives, where the virus can persist for more than two weeks. [ABSTRACT FROM AUTHOR]

The recently re-emerged mpox (monkeypox) virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide. Numerous studies have contributed to our understanding of its evolution, pathophysiology, and clinical manifestations. The current outbreak of the mpox virus depicts its novel route of transmission as a new variant. However, the exact reason for its transition from an epidemic to a pandemic remains unclear. Furthermore, other poxviruses such as vaccinia virus, variola virus, and cowpox virus, also belong to the same genus, Orthopoxvirus. In the present review, our objective was to summarize the evidence on evolution, pathophysiology, and clinical manifestations of mpox virus and its related poxviruses. The present review would aid in a better understanding of the current circulating mpox virus and its differences from other poxviruses. In addition, the shared genetic factors contributing to virulence in these Orthopoxvirus highlight their evolutionary connections and genetic similarities. While they exhibit differences in virulence, studying these genetic relationships is crucial for understanding their biology, pathogenicity, and the development of effective vaccines and antiviral therapeutics to curb mpox disease. [ABSTRACT FROM AUTHOR]

The evolutionary pressures exerted by viral infections have led to the development of various cellular proteins with potent antiviral activities, some of which are known as antiviral restriction factors. TRIpartite Motif-containing protein 5 alpha (TRIM5α) is a well-studied restriction factor of retroviruses that exhibits virus- and host-species-specific functions in protecting against cross-primate transmission of specific lentiviruses. This specificity is achieved at the level of the host gene through positive selection predominantly within its C-terminal B30.2/PRYSPRY domain, which is responsible for the highly specific recognition of retroviral capsids. However, more recent work has challenged this paradigm, demonstrating TRIM5α as a restriction factor for retroelements as well as phylogenetically distinct viral families, acting similarly through the recognition of viral gene products via B30.2/PRYSPRY. This spectrum of antiviral activity raises questions regarding the genetic and structural plasticity of this protein as a mediator of the recognition of a potentially diverse array of viral molecular patterns. This review highlights the dynamic evolutionary footprint of the B30.2/PRYSPRY domain in response to retroviruses while exploring the guided 'specificity' conferred by the totality of TRIM5α's additional domains that may account for its recently identified promiscuity. [ABSTRACT FROM AUTHOR]

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ABSTRACT Mpox disease, caused by the monkeypox virus (MPXV), was recently classified as a public health emergency of international concern due to its high lethality and pandemic potential. MPXV is a zoonotic disease that emerged and is primarily spread by small rodents. Historically, it was considered mainly zoonotic and not likely to sustain human-to-human transmission. However, the worldwide outbreak of Clade IIb MPXV from 2020 to 2022 and ongoing Clade I MPXV epidemics in the Democratic Republic of the Congo and surrounding areas are a warning that human-adapted MPXVs will continually arise. Understanding the viral genetic determinants of host range, pathogenesis, and immune evasion is imperative for developing control strategies and predicting the future of Mpox. Here, we delve into the MPXV genome to detail genes involved in host immune evasion strategies for this zoonotic rodent-borne and human-circulating virus. We compare MPXV gene content to related Orthopoxviruses, which have narrow host ranges, to identify potential genes involved in species-specific pathogenesis and host tropism. In addition, we cover the key virulence factor differences that distinguish the MPXV clade lineages. Finally, we dissect how genomic reduction of Orthopoxviruses, through various molecular mechanisms, is contributing to the generation of novel MPXV lineages with increased human adaptation. This review aims to highlight gene content that defines the MPXV species, MPXV clades, and novel MPXV lineages that have culminated in this virus being elevated to a public health emergency of national concern.

Relevance. After smallpox eradication, in conditions of population immunity to orthopoxviruses absence, Monkeypox virus became most significant orthopoxvirus, pathogenic for humans. Therefore the generalization of data on the areas of infection outbreaks, human diseases and methods of prevention and treatment of monkey pox is important task. Aim. To characterize the problem of monkeypox in the world based on an analysis of foreign scientific publications over the past 20 years. Materials and methods. The work used publications presented in the main international medical information databases PubMed, Web of Science, Embase, etc. To analyze the publications, the analytical epidemiological method was used. Results and discussion. Monkeypox virus, obtained and identified in 1958, by genetic and phenotypic differences divides on two clades: West-African with lethality 3.6% and Central-African (Congo Basin) with lethality 10%. Monkeypox virus transmission to men happens in two ways, either from animal-to-human or human-to-human. Monkey pox is endemic only on African continent, but In 2003 year the first outbreak, numbering 47 confirmed cases, was occurred in non-endemic country – USA and the largest monkeypox outbreak began in Nigeria in September 2017 year and continue to the present. Comparison of the genome sequences of strains, isolated from patients in non-endemic countries, showed, that it genetically close to West-african strains, belong to II clades and were descended from a common ancestor. Many cases of disease in humans in the current outbreak have been traced to sexual transmission especially among men, who identify ourselves as gay or bisexual. The basis method for identification of agent in present time is PCR-RT targeting on the tumor necrosis factor (TNF) receptor gene. Usually monkeypox of human is mild, self-limiting disease. The symptoms of monkeypox are varied and non-specific. One of the most frequently observed clinical symptoms is lymphadenopathy. Most patients recover during some weeks. However, specific antiviral treatment – tecovirimat (S-246) and brincidofovir (CMX-001) – may be used for seriously ill or immunocompromised individuals. For prophylactic disease in present time are use vaccines JYNNEOSTM, ACAM2000R and Aventis Pasteur (APSV). Conclusion. General vaccination against monkeypox don't develop accordingly to modern recommendations WHO. Ring vaccination is recommended to conduct for suppression of spread virus in nidus of infection among population. Timely international coordination is needed to prevent the global spread of a disease with epidemic potential.

The purpose of this study is to evaluate the effect of dose and frequency of immunization of BALB/c mice with intradermal (ID) injection of the LIVP strain of vaccinia virus (VACV) on the level of their protection against the ectromelia virus (ECTV), which is highly virulent for mice. Immunization of mice was carried out using a single or double ID injection of VACV LIVP with an interval of 28 days at a dose of 105 plaque-forming units (PFU), as well as a single injection at a dose of 106 PFU. In blood sera taken from mice during their lifetime, the dynamics of biosynthesis of VACV-specific IgG was determined with enzyme-linked immunosorbent assay (ELISA) up to 140 days postvaccination (dpv). At 142 dpv, groups immunized with the LIVP virus and control animals were intranasally infected with a lethal dose of ECTV and the indicators of clinical manifestations of infection, body weight of animals, and their death were monitored. At 28 dpv the level of antibodies in mice vaccinated with VACV LIVP at a dose of 106 PFU significantly exceeded this level in mice vaccinated with the same virus at a dose of 105 PFU. Repeated immunization with VACV LIVP at a dose of 105 PFU on 28 dpv led to a significant increase in the biosynthesis of virus-specific IgG and the level of analyzed antibodies in this group of mice corresponded to a similar indicator for the group of mice vaccinated once with VACV LIVP at a dose of 106 PFU. After infection with a lethal dose of ECTV, all animals in the control group (unvaccinated) died by the eighth day after infection, while those vaccinated with VACV LIVP once at a dose of 105 PFU died by the 14th day. In groups of mice vaccinated twice at a dose of 105 PFU and once at a dose of 106 PFU, 80% of the subjects survived. To maintain a long-term protective immune response to vaccination with live VACV, a high dose of this virus must be used. Alternatively, a lower vaccination dose can be used, but in this case, revaccination should be carried out. [ABSTRACT FROM AUTHOR]

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat. [ABSTRACT FROM AUTHOR]

After the abolition of the mandatory smallpox vaccination, the humanity lost the immunity not only to smallpox, but also to infections caused by pathogens of this family (Orthopoxvirus): monkeypox, cowpox, buffalo pox, camelpox. Since the camelpox and African gerbil viruses are the closest to the variola virus (genomic homology is 97%) in phylogenetic and genetic terms, it cannot be ruled out that a mutation in a small fragment of the genome of one of these viruses will lead to the replacement of a relatively safe virus with an epidemically dangerous pathogen. The purpose of is article is to summarize materials on the study of camelpox virus. The sources for this research is scientific articles and other English-language literature available via the Internet. The research method is an analysis of scientific sources on camelpox from the general to the specific. The authors considered the epizootic danger of the virus, its virulence for humans, phylogenetic relationship with other orthopoxviruses, means of specific prevention and treatment of camel pox in camels. The discussion and the results. The causative agent of camelpox causes a nodular-pastular rash on the skin and mucous membranes in Camelus dromedaries and Camelus bactrianus. The disease is contagious, and its epizootics lead to significant economic damage. From December 2008 to May 2009, several laboratory-confirmed cases of camelpox in humans were reported in India, Somalia and eastern Sudan. Nowadays for the identification of the camelpox virus, a RT-PCR test system with primers for the C18L gene is usually offered, which detects only this virus. The established host range of the virus is limited to one animal - the camel. To treat sick camels, chemotherapy drugs are used: cidofovir and tocoverimate (ST-246). For immunoprophylaxis, live and inactivated vaccines are used. The conclusion. Camelpox virus poses a risk to humans in regions where people raise camels and are in close contact with them. The immunodeficient populations of people may serve as an additional «window» for the penetration of this virus into human society. The genetic variability of the virus and the plasticity of its genome make it possible to obtain virus strains with altered properties. Synthetic biology methods create a risk, through small substitutions in the genome of the virus, of turning it into an epidemic danger for humans. Constant monitoring of this disease is necessary, since there is a danger of the transmission of camelpox from Kazakhstan to areas bordering the Russian Federation.

Abstract Objectives The purpose of this study was to evaluate possible factors that might be accompanied by high level of human monkey pox (HMPX) knowledge and to explain the relationship between HMPX knowledge and Beliefs regarding emerging viral infections. Study design A descriptive cross-sectional study was conducted for the implementation of this study. Methods Study was conducted at two general hospitals in Mansoura City (Old General Hospital and International Hospital) El Dakahlia Governorate among 620 healthcare workers (HCWs) using a self-managed questionnaire for 1 week (1 to 7 January 2023). The questionnaire has items adapted from the previously published literature to assess HMPX knowledge and Beliefs regarding emerging viral infections. Results The mean age of the study sample was 27.97 years and most of them were female (86.1%). Physicians and other HCWs (nurses, laboratory technicians, radiographer technicians, and pharmacists) had significantly different levels of knowledge of monkeypox for the majority of the questions. A higher belief was found among two items: viruses are biological weapons manufactured by the superpowers to take global control and the government is misleading the public about the cause of the virus. Conclusion This study discovered lower levels of knowledge of HMPX among HCWs in Egypt. Beliefs about emerging viral infections were widespread, and future research should look into their potential negative impact on health behavior.

Monkeypox (now Mpox), a zoonotic disease caused by the monkeypox virus (MPXV) is an emerging threat to global health. In the time span of only six months, from May to October 2022, the number of MPXV cases breached 80,000 and many of the outbreaks occurred in locations that had never previously reported MPXV. Currently there are no FDA-approved MPXV-specific vaccines or treatments, therefore, finding drugs to combat MPXV is of utmost importance. The A42R profilin-like protein of the MPXV is involved in cell development and motility making it a critical drug target. A42R protein is highly conserved across orthopoxviruses, thus A42R inhibitors may work for other family members. This study sought to identify potential A42R inhibitors for MPXV treatment using computational approaches. The energy minimized 3D structure of the A42R profilin-like protein (PDB ID: 4QWO) underwent virtual screening using a library of 36,366 compounds from Traditional Chinese Medicine (TCM), AfroDb, and PubChem databases as well as known inhibitor tecovirimat via AutoDock Vina. A total of seven compounds comprising PubChem CID: 11371962, ZINC000000899909, ZINC000001632866, ZINC000015151344, ZINC000013378519, ZINC000000086470, and ZINC000095486204, predicted to have favorable binding were shortlisted. Molecular docking suggested that all seven proposed compounds have higher binding affinities to A42R (-7.2 to -8.3 kcal/mol) than tecovirimat (-6.7 kcal/mol). This was corroborated by MM/PBSA calculations, with tecovirimat demonstrating the highest binding free energy of - 68.694 kJ/mol (lowest binding affinity) compared to the seven shortlisted compounds that ranged from -73.252 to -97.140 kJ/mol. Furthermore, the 7 compounds in complex with A42R demonstrated higher stability than the A42Rtecovirimat complex when subjected to 100 ns molecular dynamics simulations. The protein-ligand interaction maps generated using LigPlot+ suggested that residues Met; Glu3, Trp4, Ile7, Arg127, Val128, Thr131, and Asn133 are important for binding. These seven compounds were adequately profiled to be potential antivirals via PASS predictions and structural similarity searches. All seven potential lead compounds were scored Pa > Pi for antiviral activity while ZINC000001632866 and ZINC000015151344 were predicted as poxvirus inhibitors with Pa values of 0.315 and 0.215, and Pi values of 0.052 and 0.136, respectively. Further experimental validations of the identified lead compounds are required to corroborate their predicted activity. These seven identified compounds represent solid footing for development of antivirals against MPXV and other orthopoxviruses. [ABSTRACT FROM AUTHOR]

A global outbreak of predominantly sexually transmitted mpox infections, outside endemic regions, was reported in May 2022. Thereafter, risk groups were vaccinated against smallpox, a structurally related orthopoxvirus. In the current study, we analyzed T cell responses against peptides derived from orthopoxviruses in 33 HIV-positive patients after two vaccinations against smallpox and in 10 patients after mpox infection. We established an ELISpot assay, detecting either the secretion of the pro-inflammatory cytokine interferon (IFN)-γ or interleukin (IL)-2. After vaccination, 21 out of 33 patients (64%) showed specific IFN-γ secretion and 18 (55%) specific IL-2 secretion, defined as >3-fold higher specific value than negative control and at least 4 spots above the negative control. After mpox infection, all patients showed specific IFN-γ secretion and 7 out of 10 (70%) IL-2 secretion. In vaccinated patients, IFN-γ responses were significantly lower than in patients with mpox infection (median response 4.5 vs. 21.0 spots, p < 0.001). The same trend was observed for IL-2 responses. After mpox infection, IL-2 ELISpot results positively correlated with CD8+ T cells (p < 0.05). Thus, T cell responses were detectable in two thirds of HIV-positive patients after vaccination and were even more abundant and vigorous after mpox infection. [ABSTRACT FROM AUTHOR]

Monkeypox is an emerging zoonotic disease caused by the monkeypox virus (MPXV) and shares similarities with the other Orthopoxviruses. This review aimed to explore the morphology of MPXV, clinical manifestations, and mitigation strategies in the developing nations. Clinically, MPXV resembles smallpox. It has an unidentified natural host, despite it has been isolated from the rope squirrels and Sooty mangabeys. Transmission occurs through the respiratory excretions, saliva, contact with lesions, and potentially via the feces. The disease comprises a prodromal phase and subsequent skin rash. Originating in 1959 following a monkey outbreak in Copenhagen's research institute; the initial human case was documented in 1970 in the Democratic Republic of Congo. The virus subsequently dispersed globally; impacting several nations such as UK, USA, Israel, and Singapore. Thus, in addition to the healthcare infrastructure, combating monkeypox in the developing countries requires bolstering the disease surveillance, public awareness, diagnostic capabilities, and vaccination campaigns. Sustainable international collaboration and extensive scientific investigations are crucial for safeguarding the public health and preventing further spread of this viral disease.

Introduction. Following the successful eradication of smallpox, mass vaccination against this disease was discontinued in 1980. The unvaccinated population continues to be at risk of infection due to military use of variola virus or exposure to monkeypox virus in Africa and non-endemic areas. In cases of these diseases, rapid diagnosis is of great importance, since the promptness and effectiveness of therapeutic and quarantine measures depend on it. The aim of work is to develop a kit of reagents for enzyme-linked immunosorbent assay (ELISA) for fast and highly sensitive detection of orthopoxviruses (OPV) in clinical samples. Materials and methods. The efficiency of virus detection was evaluated by single-stage ELISA in the cryolisate of CV-1 cell culture samples infected with vaccinia, cowpox, rabbitpox, and ectromelia viruses, as well as in clinical samples of infected rabbits and mice. Results. The method of rapid ELISA was shown to allow the detection of OPV in crude viral samples in the range of 5.0 1025.0 103 PFU/ml, and in clinical samples with a viral load exceeding 5 103 PFU/ml. Conclusions. The assay involves a minimum number of operations and can be performed within 45 minutes, which makes it possible to use it in conditions of a high level of biosecurity. Rapid ELISA method was developed using polyclonal antibodies, which significantly simplifies and reduces the cost of manufacturing a diagnostic system.

Monkeypox (now Mpox), a zoonotic disease caused by the monkeypox virus (MPXV) is an emerging threat to global health. In the time span of only six months, from May to October 2022, the number of MPXV cases breached 80,000 and many of the outbreaks occurred in locations that had never previously reported MPXV. Currently there are no FDA-approved MPXV-specific vaccines or treatments, therefore, finding drugs to combat MPXV is of utmost importance. The A42R profilin-like protein of the MPXV is involved in cell development and motility making it a critical drug target. A42R protein is highly conserved across orthopoxviruses, thus A42R inhibitors may work for other family members. This study sought to identify potential A42R inhibitors for MPXV treatment using computational approaches. The energy minimized 3D structure of the A42R profilin-like protein (PDB ID: 4QWO) underwent virtual screening using a library of 36,366 compounds from Traditional Chinese Medicine (TCM), AfroDb, and PubChem databases as well as known inhibitor tecovirimat via AutoDock Vina. A total of seven compounds comprising PubChem CID: 11371962, ZINC000000899909, ZINC000001632866, ZINC000015151344, ZINC000013378519, ZINC000000086470, and ZINC000095486204, predicted to have favorable binding were shortlisted. Molecular docking suggested that all seven proposed compounds have higher binding affinities to A42R (–7.2 to –8.3 kcal/mol) than tecovirimat (–6.7 kcal/mol). This was corroborated by MM/PBSA calculations, with tecovirimat demonstrating the highest binding free energy of –68.694 kJ/mol (lowest binding affinity) compared to the seven shortlisted compounds that ranged from –73.252 to –97.140 kJ/mol. Furthermore, the 7 compounds in complex with A42R demonstrated higher stability than the A42R-tecovirimat complex when subjected to 100 ns molecular dynamics simulations. The protein-ligand interaction maps generated using LigPlot+ suggested that residues Met1, Glu3, Trp4, Ile7, Arg127, Val128, Thr131, and Asn133 are important for binding. These seven compounds were adequately profiled to be potential antivirals via PASS predictions and structural similarity searches. All seven potential lead compounds were scored Pa > Pi for antiviral activity while ZINC000001632866 and ZINC000015151344 were predicted as poxvirus inhibitors with Pa values of 0.315 and 0.215, and Pi values of 0.052 and 0.136, respectively. Further experimental validations of the identified lead compounds are required to corroborate their predicted activity. These seven identified compounds represent solid footing for development of antivirals against MPXV and other orthopoxviruses.

Mpox is a neglected zoonotic disease endemic in West and Central Africa. The Mpox outbreak with more than 90,000 cases worldwide since 2022 generated great concern about future outbreaks and highlighted the need for a simple and rapid diagnostic test. The Mpox virus, MPV, is a member of the Orthopoxvirus (OPV) genus that also contains other pathogenic viruses including variola virus, vaccinia virus, camelpox virus, and cowpox virus. Phylogenomic analysis of 200 OPV genomes identified 10 distinct phylogroups with the New World OPVs placed on a very long branch distant from the Old World OPVs. Isolates derived from infected humans were found to be distributed across multiple phylogroups interspersed with isolates from animal sources, indicating the zoonotic potential of these viruses. In this study, we developed a simple and sensitive colorimetric LAMP assay for generic detection of Old World OPVs. We also developed an MPV-specific probe that differentiates MPV from other OPVs in the N1R LAMP assay. In addition, we described an extraction-free protocol for use directly with swab eluates in LAMP assays, thereby eliminating the time and resources needed to extract DNA from the sample. Our direct LAMP assays are well-suited for low-resource settings and provide a valuable tool for rapid and scalable diagnosis and surveillance of OPVs and MPV. [ABSTRACT FROM AUTHOR]

Mpox is the most prevalent Orthopoxvirus infection in humans. Several clinical characteristics of mpox distinguish this disease from other rash illnesses. Complications are not uncommon. New therapeutics and vaccines are likely to change the course of the disease, especially in immunocompromised individuals. Clinicians must ensure that access to treatment and prevention measures are guaranteed especially in this particular population. This review exposes the epidemiology, clinical spectrum and updated considerations in treatment and prevention within the mpox global outbreak. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate possible factors that might be accompanied by high level of human monkey pox (HMPX) knowledge and to explain the relationship between HMPX knowledge and Beliefs regarding emerging viral infections. Study design: A descriptive cross-sectional study was conducted for the implementation of this study. Methods: Study was conducted at two general hospitals in Mansoura City (Old General Hospital and International Hospital) El Dakahlia Governorate among 620 healthcare workers (HCWs) using a self-managed questionnaire for 1 week (1 to 7 January 2023). The questionnaire has items adapted from the previously published literature to assess HMPX knowledge and Beliefs regarding emerging viral infections. Results: The mean age of the study sample was 27.97 years and most of them were female (86.1%). Physicians and other HCWs (nurses, laboratory technicians, radiographer technicians, and pharmacists) had significantly different levels of knowledge of monkeypox for the majority of the questions. A higher belief was found among two items: viruses are biological weapons manufactured by the superpowers to take global control and the government is misleading the public about the cause of the virus. Conclusion: This study discovered lower levels of knowledge of HMPX among HCWs in Egypt. Beliefs about emerging viral infections were widespread, and future research should look into their potential negative impact on health behavior. [ABSTRACT FROM AUTHOR]

Introduction: Compared with previous geographically localized outbreaks of monkeypox (MPOX), the scale of the 2022 global mpox outbreak has been unprecedented, yet the clinical features of this outbreak remain incompletely characterized. Methods: We identified patients diagnosed with mpox by polymerase chain reaction (PCR; n = 36) from July to September 2022 at a single, tertiary care institution in the USA. Demographics, clinical presentation, infection course, and histopathologic features were reviewed. Results and Conclusion: Men who have sex with men (89%) and people living with HIV (97%) were disproportionately affected. While fever and chills (56%) were common, some patients (23%) denied any prodromal symptoms. Skin lesions showed a wide range of morphologies, including papules and pustules, and lesions showed localized, not generalized, spread. Erythema was also less appreciable in skin of colour patients (74%). Atypical clinical features and intercurrent skin diseases masked the clinical recognition of several cases, which were ultimately diagnosed by PCR. Biopsies showed viral cytopathic changes consistent with Orthopoxvirus infections. All patients in this case series recovered without complications, although six patients (17%) with severe symptoms were treated with tecovirimat without complication. [ABSTRACT FROM AUTHOR]

In 1980, the World Health Assembly officially declared smallpox eradicated in the world, which allowed developed countries to stop preventive vaccination against this disease. However, circulating and emerging orthopoxviruses along with the lack of herd immunity prompt the need for emergency smallpox vaccines meeting the current requirements for biologicals.The aim of the study was to analyse the safety and efficacy of third-generation smallpox vaccines based on the MVA strain of vaccinia virus compliant with the current (stricter) immunogenicity and safety requirements in healthy subjects and especially in patients with underlying health conditions, considering the lack of herd immunity to orthopoxviruses.The authors analysed the existing experience with smallpox vaccines. The vaccines based on the modified vaccinia Ankara (MVA) strain hold a special place amongst other third-generation vaccines, as this strain is safe and can be used for creating vector vaccines. Bavarian Nordic produces the MVA-based vaccine under three brand names (Imvanex in the EU, Jynneos™ in the USA, and IMVAMUNE® in Canada). According to the results of MVA-based vaccine clinical trials in healthy volunteers and patients with various underlying conditions, the main mild adverse drug reactions (erythema, pain, pruritus, and swelling) were mostly registered at the injection site. The systemic adverse drug reactions included fatigue, headache, myalgia, and chills; several subjects developed upper respiratory tract infections, nausea, and gastroenteritis, which resolved spontaneously within a day. MVA-based vaccines did not cause any cardiac abnormalities, including myo- or pericarditis. Thus, the vaccines may be used in patients with eczema, atopic dermatitis, inflammatory skin conditions, HIV, tuberculosis, cardiac abnormalities, as well as in children, adolescents, and pregnant women. The optimal intradermal immunisation dose was 1×108 TCID50. Two injections at this dose induced a pronounced humoral and cell-mediated immune response comparable to that induced by one administration of a first-generation smallpox vaccine. At this dose, the study vaccine also boosted pre-existing immunity conferred by a first-generation vaccine. The US Centers for Disease Control and Prevention recommend Jynneos™ for preventing monkeypox in adults (18 years of age and older).

Human and animal infections with Orthopoxvirus have become more prevalent in recent years. Although smallpox has been eradicated, vaccinations continue to play a role in controlling the spread of Orthopoxvirus diseases. First generation vaccines were successfully commercialized, and they were widely used previously. Besides, several second-generation vaccines that emphasize sterile cell culture techniques for vaccine production have been developed. Some of the third-generation vaccines also successfully trigger immune responses in the host, and they are being researched as safer substitutes for smallpox vaccines. Extensive work is still being done on the creation of fourth-generation smallpox vaccines, which include the creation of DNA subunit vaccines. Clinical studies must be conducted to evaluate the efficacies of these vaccines. Vaccine was effective in preventing smallpox infection. To achieve the Sustainable Development Goals of the United Nations, a new paradigm for vaccination research and product development must be established. [ABSTRACT FROM AUTHOR]

Background: Human Monkeypox is a zoonotic disease. The Monkeypox virus belongs to the orthopoxvirus family, and it is a double-stranded DNA virus which is mainly found among rodents and other animals and is expected to have been transmitted incidentally to humans and is further spread through human-to-human transmission. Aim: To give a clear picture of the extent of the monkeypox virus and thereby depict the future risk of community transmission of the virus. Methods: A descriptive study has been conducted by analyzing secondary data from the Centre of Disease Control, UK and the cumulative cases and deaths are calculated. This is an evidence basis analysis which describes a clear picture of the arising risk due to the monkeypox virus. Result: It was identified that data collected from reliable sources give a clearer picture of the prevalence of the monkeypox virus among men. Conclusion: With the current knowledge of the devastation caused by the COVID-19 pandemic, it is crucial to examine pathophysiology and transmission to prevent its effect on public health and its propensity to spread like a pandemic. All the governments, health agencies and organizations along with related stakeholders must work on prevention policies to control monkeypox. [ABSTRACT FROM AUTHOR]

ABSTRACT Members of the Orthopoxvirus genus can cause severe infections in humans. Global vaccination against smallpox, caused by the variola virus, resulted in the eradication of the disease in 1980. Shortly thereafter, vaccination was discontinued, and as a result, a large proportion of the current population is not protected against orthopoxviruses. The concerns that the variola virus or other engineered forms of poxviruses may re-emerge as bioweapons and the sporadic outbreaks of zoonotic members of the family, such as Mpox, which are becoming more frequent and prevalent, also emphasize the need for an effective treatment against orthopoxviruses. To date, the most effective way to prevent or control an orthopoxvirus outbreak is through vaccination. However, the traditional vaccinia-based vaccine may cause severe side effects. Vaccinia immune globulin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of vaccine adverse reactions and was also used occasionally for the treatment of severe orthopoxvirus infections. However, this treatment carries many disadvantages and is also in short supply. Thus, a recombinant alternative is highly needed. In this study, two non-human primates were immunized with live vaccinia virus, producing a robust and diverse antibody response. A phage-display library was constructed based on the animal’s lymphatic organs, and a panel of neutralizing monoclonal antibodies (mAbs), recognizing diverse proteins of the vaccinia virus, was selected and characterized. These antibodies recognized both mature virion and enveloped virion forms of the virus and exhibited high affinity and potent in vitro neutralization capabilities. Furthermore, these monoclonal antibodies were able to neutralize Mpox 2018 and 2022 strains, suggesting a potential for cross-species protection. We suggest that a combination of these mAbs has the potential to serve as recombinant therapy both for vaccinia vaccine adverse reactions and for orthopoxvirus infections. Importance In this manuscript, we report the isolation and characterization of several recombinant neutralizing monoclonal antibodies (mAbs) identified by screening a phage-display library constructed from lymphatic cells collected from immunized non-human primates. The antibodies target several different antigens of the vaccinia virus, covering both mature virion and extracellular enveloped virion forms of the virus. We document strong evidence indicating that they exhibit excellent affinity to their respective antigens and, most importantly, optimal in vitro neutralization of the virus, which exceeded that of vaccinia immune globulin. Furthermore, we present the ability of these novel isolated mAbs (as well as the sera collected from vaccinia-immunized animals) to neutralize two Mpox strains from the 2018 to 2022 outbreaks. We believe that these antibodies have the potential to be used for the treatment of vaccinia vaccine adverse reactions, for other orthopoxvirus infections, and in cases of unexpected bioterror scenarios.

The purpose of this review is to give an up-to-date, thorough, and timely overview of monkeypox (Mpox), a severe infectious viral disease. Furthermore, this review provides an up-to-date treatment option for Mpox. The monkeypox virus (MPXV) has remained the most virulent poxvirus for humans since the elimination of smallpox approximately 41 years ago, with distribution mainly in central and west Africa. Mpox in humans is a zoonotically transferred disease that results in symptoms like those of smallpox. It had spread throughout west and central Africa when it was first diagnosed in the Republic of Congo in 1970. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease's global significance. A better understanding of Mpox's dynamic epidemiology may be attained by increased surveillance and identification of cases. [ABSTRACT FROM AUTHOR]

Monkeypox has emerged as the most significant human pathogen in recent times and is a rapidly growing threat to public health globally. Monkeypox virus is an orthopoxvirus, that belongs to the Poxviridae family. The smallpox virus also belongs to this family. Monkeypox virus, endemic to Central and West Africa can infect various animal species but can also transmit to humans. Monkeypox viruses circulate among wild animals and usually spread to people when they eat or have other close contacts with infected animals. Getting bitten or scratched by the infected animal, direct contact with its bodily fluids, blood, blisters or scabs; indirect contact with lesion material, e.g. contaminated bedding, linens and even eating the undercooked animal infected with monkeypox, could result in transmission. Among humans, Monkeypox is contracted through close physical contact, and contact with contaminated materials. Monkeypox presents with fever, headaches, myalgia, and enlarged lymph nodes. This is followed by a rash that starts from mouth to face and spreads to the trunk and arms. The illness is usually mild and patients fully recover within four weeks. Nucleic acid testing (NAT) is the primary diagnostic tool for detection. Polymerase chain reaction (PCR) is the preferred method for NAT. Treatment is mainly supportive and is directed to alleviate symptoms, prevent long-term sequelae and mitigate disease spread. Patients require isolation and symptomatic care. The smallpox vaccine, antiviral agents and vaccinia immunoglobulin (VIG) have been used in earlier outbreaks but sufficient evidence to recommend their use is still lacking.

The monkeypox virus (MPXV) is the cause of a zoonotic infection similar to smallpox. Although it is endemic to Africa, it has recently begun to circulate in other parts of the world. In July 2022, the World Health Organization declared monkeypox an international public health emergency. This review aims to provide an overview of this neglected zoonotic pathogen. MPXV circulates as two distinct clades, the Central African and West African, with case fatality rates of 10.6% and 3.6%, respectively. The risk of infection is greater for those who work with animals or infected individuals. The virus’ entry into the human body provokes both natural and acquired immunity. Although natural killer cells, CD4 + T cells, and CD8 + T cells play an essential role in eradicating MPXV, there is still a gap in the understanding of the host immune response to the virus. Currently, there are no specific therapeutic guidelines for treating monkeypox; however, some antiviral drugs such as tecovirimat and cidofovir may help to abate the severity of the disease. The use of nonpharmaceutical interventions and immunization can reduce the risk of infection. Increased surveillance and identification of monkeypox cases are crucial to understand the constantly shifting epidemiology of this resurging and intimidating disease. The present review provides a detailed perspective on the emergence and circulation of MPXV in human populations, infection risks, human immune response, disease diagnosis and prevention strategies, and future implications, and highlights the importance of the research community engaging more with this disease for an effective global response.

The 2022 monkeypox outbreak has created a new global health threat and pandemic. Monkeypox virus is a descendant of the genus Orthopoxvirus, producing a febrile skin rash disease in humans. Monkeypox is zoonotic transmitted and transmitted from human to human in several ways. Even though this disease is self-limited, it creates important community health worries due to its inconvenience and widespread complications. Herein, we discussed the up-to-date current situation of monkeypox regarding its epidemiology, clinical manifestations, current in-use therapeutics, necessary protective measures, and response to potential occurrences considering the recent pandemic. Also, in this review, a comparative genomic analysis of the recent circulating strains that have been recovered from various countries including, Egypt, USA, Spain, Japan and South Africa has been investigated.

The human monkeypox virus (MPV), a zoonotic illness that was hitherto solely prevalent in Central and West Africa, has lately been discovered to infect people all over the world and has become a major threat to global health. Humans unintentionally contract this zoonotic orthopoxvirus, which resembles smallpox, when they come into contact with infected animals. Studies show that the illness can also be transferred through frequent proximity, respiratory droplets, and household linens such as towels and bedding. However, MPV infection does not presently have a specified therapy. Smallpox vaccinations provide cross-protection against MPV because of antigenic similarities. Despite scant knowledge of the genesis, epidemiology, and ecology of the illness, the incidence and geographic distribution of monkeypox outbreaks have grown recently. Polymerase chain reaction technique on lesion specimens can be used to detect MPV. Vaccines like ACAM2000, vaccinia immune globulin intravenous (VIG-IV), and JYNNEOS (brand name: Imvamune or Imvanex) as well as FDA-approved antiviral medications such as brincidofovir (brand name: Tembexa), tecovirimat (brand name: TPOXX or ST-246), and cidofovir (brand name: Vistide) are used as therapeutic medications against MPV. In this overview, we provide an outline of the MPV's morphology, evolution, mechanism, transmission, diagnosis, preventative measures, and therapeutic approaches. This study offers the fundamental information required to prevent and manage any further spread of this emerging virus. [ABSTRACT FROM AUTHOR]

The paper highlights the current knowledge on infection biology, epidemiology and evolution of monkeypox virus (MPXV), cowpox virus (CPXV), buffalopox virus (CPXV), camelpox virus (CMLPV), as well as addresses some factors that modulate dynamics of orthopoxvirus transmission, manifestation of orthopoxvirus infections and their preservation in nature. Despite the elimination of the historically infamous smallpox, orthopoxviruses remain a serious veterinary and health problem. Their role is currently increasing while the number of persons not immune to smallpox grows. Along with this, there is a genetic transformation of pathogens. In this regard, the risks of human infection with orthopoxviruses of zoonotic nature are increasing. The problem of monkeypox, cowpox, buffalopox and camelpox and the respective agents included in the genus of zoonotic orthopox viruses presents the greatest interest. Along with the increased number of human monkeypox cases in 2020–2022, a retrospective analysis of the last 20 years shows that the activity of monkeypox outbreaks in the XXI century intensified in Central African countries. Cowpox outbreaks in Europe and camelpox outbreaks in Southwestern and Central Asia have also become more active. In 2011, in India, the camelpox virus overcame the interspecies barrier and caused a clinical pox-like disease in humans. Scientists are alarmed by these facts as the camelpox virus genomeis 99% homologous to the genome of the small poxvirus. This requires strengthening the epizootological and epidemiological monitoring of orthopoxvirus zoonotic pathogens.

ABSTRACT Viruses with large, double-stranded DNA genomes captured the majority of their genes from their hosts at different stages of evolution. The origins of many virus genes are readily detected through significant sequence similarity with cellular homologs. In particular, this is the case for virus enzymes, such as DNA and RNA polymerases or nucleotide kinases, that retain their catalytic activity after capture by an ancestral virus. However, a large fraction of virus genes have no readily detectable cellular homologs, meaning that their origins remain enigmatic. We explored the potential origins of such proteins that are encoded in the genomes of orthopoxviruses, a thoroughly studied virus genus that includes major human pathogens. To this end, we used AlphaFold2 to predict the structures of all 214 proteins that are encoded by orthopoxviruses. Among the proteins of unknown provenance, structure prediction yielded clear indications of origin for 14 of them and validated several inferences that were previously made via sequence analysis. A notable emerging trend is the exaptation of enzymes from cellular organisms for nonenzymatic, structural roles in virus reproduction that is accompanied by the disruption of catalytic sites and by an overall drastic divergence that precludes homology detection at the sequence level. Among the 16 orthopoxvirus proteins that were found to be inactivated enzyme derivatives are the poxvirus replication processivity factor A20, which is an inactivated NAD-dependent DNA ligase; the major core protein A3, which is an inactivated deubiquitinase; F11, which is an inactivated prolyl hydroxylase; and more similar cases. For nearly one-third of the orthopoxvirus virion proteins, no significantly similar structures were identified, suggesting exaptation with subsequent major structural rearrangement that yielded unique protein folds. IMPORTANCE Protein structures are more strongly conserved in evolution than are amino acid sequences. Comparative structural analysis is particularly important for inferring the origins of viral proteins that typically evolve at high rates. We used a powerful protein structure modeling method, namely, AlphaFold2, to model the structures of all orthopoxvirus proteins and compared them to all available protein structures. Multiple cases of recruitment of host enzymes for structural roles in viruses, accompanied by the disruption of catalytic sites, were discovered. However, many viral proteins appear to have evolved unique structural folds.

Monkeypox is an infectious disease caused by an orthopoxvirus. It is characterized in particular by a rash occurring within 1 to 3 days after an initial non-specific phase. Cases not directly linked to a trip to Central or West Africa or people returning from a trip have been reported in many countries and the situation is therefore changing very quickly. In France, 4,982 cases of monkeypox have been identified to date. The significant and sudden increase from April 2022 in the number of autochthonous cases in several regions not endemic for MPXV and far from each other, by human-to-human transmission, makes this virus an emerging biological pathogen. How does this infection present and how to prevent it? [ABSTRACT FROM AUTHOR]

Orthopoxviruses (OPXVs) belong to a group of nucleo-cytoplasmic large DNA viruses. Human pathogenic OPXVs (hpOPXVs) include at least five viruses, among which smallpox virus and monkeypox virus are the most dangerous viral pathogens. Both viruses are classified as category-one human infectious pathogens in China. Although smallpox was globally eradicated in the 1980 s, it is still a top biosecurity threat owing to the possibility of either being leaked to the outside world from a laboratory or being weaponized by terrorists. Beginning in early May 2022, a sudden outbreak of monkeypox was concurrently reported in more than 100 disparate geographical areas, representing a public health emergency of international concern, as declared by the World Health Organization (WHO). In this review, we present the reasons for hpOPXVs such as monkeypox virus presenting a potential threat to public health. We then systematically review the historical and recent development of vaccines and drugs against smallpox and monkeypox. In the final section, we highlight the importance of viromics studies as an integral part of a forward defense strategy to eliminate the potential threat to public health from emerging or re-emerging hpOPXVs and their variants. [ABSTRACT FROM AUTHOR]

The eradication of smallpox was an enormous achievement due to the global vaccination program launched by World Health Organization. The cessation of the vaccination program led to steadily declining herd immunity against smallpox, causing a health emergency of global concern. The smallpox vaccines induced strong, humoral, and cell-mediated immune responses, protecting for decades after immunization, not only against smallpox but also against other zoonotic orthopoxviruses that now represent a significant threat to public health. Here we review the major aspects regarding orthopoxviruses' zoonotic infections, factors responsible for viral transmissions, as well as the emerging problem of the increased number of monkeypox cases recently reported. The development of prophylactic measures against poxvirus infections, especially the current threat caused by the monkeypox virus, requires a profound understanding of poxvirus immunobiology. The utilization of animal and cell line models has provided good insight into host antiviral defenses as well as orthopoxvirus evasion mechanisms. To survive within a host, orthopoxviruses encode a large number of proteins that subvert inflammatory and immune pathways. The circumvention of viral evasion strategies and the enhancement of major host defenses are key in designing novel, safer vaccines, and should become the targets of antiviral therapies in treating poxvirus infections. [ABSTRACT FROM AUTHOR]

The orthopoxvirus (OPV) genus includes several species that infect humans, including variola, monkeypox, vaccinia, and cowpox. Variola and monkeypox are often life‐threatening diseases, while vaccinia and cowpox are usually associated with local lesions. The epidemic potential for OPVs may be lower than respiratory‐borne viruses or RNA viruses. However, OPVs are notable for their spread and distribution in different environments and among different hosts. The emergence or re‐emergence of OPVs in the human population can also occur in wild or domestic animals as intermediate hosts. More effective and safer vaccines for poxvirus can be developed by understanding how immunity is regulated in poxvirus and vaccines for DNA viruses. Downstream events in cells affected by the virus are regulated functionally by a series of characteristics that are affected by host cell interactions and responses of cells against viral infections, including the interferon pathway and apoptosis. Furthermore, infection outcome is greatly influenced by the distinct selection of host‐range and immune‐modulatory genes that confer the potential for pathogenesis and host‐to‐host transmission and the distinct host‐range properties of each immune‐modulatory gene. The present study reviewed the effective factors in human‐restricted tropism and virus pathogenicity in OPVs. [ABSTRACT FROM AUTHOR]

Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. Methods: The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. Results: The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Conclusion: Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments. [ABSTRACT FROM AUTHOR]