Human Monkeypox Virus Research Articles

Exploration of natural compounds against the human mpox virus DNA-dependent RNA polymerase in silico

BackgroundLast year, the human monkeypox virus (hMPXV) emerged as an alarming threat to the community, with a detectable outbreak outside the African continent for the first time. According to The American Centers for Disease Control and Prevention (CDC), the virus is reported globally, with 86,746 confirmed cases (until April 08, 2023). DNA-dependent RNA polymerase (DdRp) is an essential protein for viral replication; hence it is a promising drug target for developing antiviral drugs against DNA viruses. Therefore, this study was conducted to search for natural compounds that could provide scaffolds for RNA polymerase inhibitors. MethodsIn this study, the DdRp structure of hMPXV was modeled and used to screen the natural compounds database (COCONUT). The virtual screening revealed 15 compounds able to tightly bind to the active site of the DdRp (binding energies less than −7.0 kcal/mol) compared to the physiological nucleotide, guanosine triphosphate (GTP). Molecular dynamics simulation was then performed on the top four hits and compared to GTP ResultsThe results revealed the potential of four compounds (comp289, comp295, comp441, and comp449) in binding the hMPXV DdRp active site with a comparable binding affinity (−17.06 ± 2.96, −11.6 ± 5.34, −14.85 ± 2.66, and −10.79 ± 4.49 kcal/mol) with GTP (−21.03 ± 7.55 kcal/mol) ConclusionThese findings may also pave the way for developing new hMPXV inhibitors based on natural product scaffolds. These results need further experimental validation but promising as it was validated by unbiased all-atom MD simulations and binding free energy calculations.

Monkeypox outbreak: observational analysis of confirmed human monkeypox virus cases in the province of padua

Monkeypox outbreak: observational analysis of confirmed human monkeypox virus cases in the province of padua

Monkeypox in Syria: Highlighting an awareness issue

BackgroundThe World Health Organization (WHO) verified 780 cases of monkeypox across 27 countries between 13 May 2022 and 2 June 2022. The aim of our study was to assess the level of awareness of human monkeypox virus among Syrian medical students, general practitioners, medical residents, and specialists. MethodsA cross-sectional online survey was performed in Syria between May 2 and September 8, 2022. The survey consisted of 53 questions within the following three categories: demographic information, work-related details, and monkeypox knowledge. ResultsIn total, 1257 Syrian healthcare workers and medical students were enrolled in our study. The animal host and incubation time for monkeypox were correctly identified by just 2.7% and 33.3% of responders, respectively. Sixty percent of the study sample thought that the symptoms of monkeypox and smallpox are identical. No statistically significant associations were found between predictor variables and knowledge regarding monkeypox (p-value > 0.05). ConclusionEducation and awareness regarding monkeypox vaccinations are of paramount importance. It is essential that clinical doctors are adequately aware of this disease, in order to avoid an uncontrolled situation, as experienced with COVID-19.

Hotel employees' knowledge of monkeypox's source, symptoms, transmission, prevention, and treatment in Egypt

BackgroundThe re-emerging human monkeypox virus (MPXV) poses a global threat. The rising number of confirmed MPXV cases worldwide is a significant reason for concern. This study aims to investigate (1) hotel employees' knowledge in Egypt of MPXV source, signs/symptoms, transmission, prevention, and treatment, (2) the primary sources of their information about MPXV, (3) whether or not they received information about MPXV from their hotels, and (4) the differences of employees’ knowledge in terms of gender, age, marital status, level of education, type of contract, professional category, hotel department, type of hotel, seniority in the hotel, and the number of hotel rooms. MethodsUsing a quantitative approach, we collected data from 453 employees in Egyptian hotels via a web-based questionnaire. The survey included questions regarding the MPXV source, signs/symptoms, transmission, prevention, and treatment, as well as its primary information sources. The questionnaire also included questions regarding participants’ demographics and hotel characteristics. ResultsThe findings indicated that more than half of hotel employees have inadequate knowledge of MPXV. Additionally, the majority of employees selected social media as their primary source of MPXV-related information. Surprisingly, most participants reported that their hotels neglected to provide them with the MPXV's information. Age, marital status, education, professional category, and tenure in the hotel all have a significant impact on their MPXV knowledge level. ConclusionThe current paper presents significant implications for both theory and practice. This study provides government agencies and hotels with guidelines for preventing the outbreak of MPXV. According to our knowledge, this is the first study conducted with hotel employees in the MPXV Egyptian context.

Recent Advances in Research and Management of Human Monkeypox Virus: An Emerging Global Health Threat.

In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of the Congo (DRC). In this study, researchers analyzed data from Central Africa: two distinct MPXV clades were confirmed by sequencing the genomes of MPXV isolates from Western Africa, the United States, and Central Africa. By comparing open reading frames across MPXV clades, scientists can infer which virus proteins might account for the observed variation in pathogenicity in humans. Monkeypox can be prevented and controlled with a better understanding of MPXV's molecular etiology and epidemiological and clinical features. In light of the current outbreaks worldwide, we provide updated information on monkeypox for medical professionals in this review.

Human Monkeypox Virus (hMPXV) Remerges - Another Global Health Concern during the COVID-19 Disaster

Human Monkeypox Virus (hMPXV) Remerges - Another Global Health Concern during the COVID-19 Disaster

Deciphering the complete human-monkeypox virus interactome: Identifying immune responses and potential drug targets.

Monkeypox virus (MPXV) is a dsDNA virus, belonging to Poxviridae family. The outbreak of monkeypox disease in humans is critical in European and Western countries, owing to its origin in African regions. The highest number of cases of the disease were found in the United States, followed by Spain and Brazil. Understanding the complete infection mechanism of diverse MPXV strains and their interaction with humans is important for therapeutic drug development, and to avoid any future epidemics. Using computational systems biology, we deciphered the genome-wide protein-protein interactions (PPIs) between 22 MPXV strains and human proteome. Based on phylogenomics and disease severity, 3 different strains of MPXV: Zaire-96-I-16, MPXV-UK_P2, and MPXV_USA_2022_MA001 were selected for comparative functional analysis of the proteins involved in the interactions. On an average, we predicted around 92,880 non-redundant PPIs between human and MPXV proteomes, involving 8014 host and 116 pathogen proteins from the 3 strains. The gene ontology (GO) enrichment analysis revealed 10,624 common GO terms in which the host proteins of 3 strains were highly enriched. These include significant GO terms such as platelet activation (GO:0030168), GABA-A receptor complex (GO:1902711), and metalloendopeptidase activity (GO:0004222). The host proteins were also significantly enriched in calcium signaling pathway (hsa04020), MAPK signaling pathway (hsa04010), and inflammatory mediator regulation of TRP channels (hsa04750). These significantly enriched GO terms and KEGG pathways are known to be implicated in immunomodulatory and therapeutic role in humans during viral infection. The protein hubs analysis revealed that most of the MPXV proteins form hubs with the protein kinases and AGC kinase C-terminal domains. Furthermore, subcellular localization revealed that most of the human proteins were localized in cytoplasm (29.22%) and nucleus (26.79%). A few drugs including Fostamatinib, Tamoxifen and others were identified as potential drug candidates against the monkeypox virus disease. This study reports the genome-scale PPIs elucidation in human-monkeypox virus pathosystem, thus facilitating the research community with functional insights into the monkeypox disease infection mechanism and augment the drug development.

Phylogenetic landscape of Monkeypox Virus (MPV) during the early outbreak in New York City, 2022

ABSTRACT Monkeypox (MPOX) is a zoonotic disease endemic to regions of Central/Western Africa. The geographic endemicity of MPV has expanded, broadening the human-monkeypox virus interface and its potential for spillover. Since May 2022, a large multi-country MPV outbreak with no proven links to endemic countries has originated in Europe and has rapidly expanded around the globe, setting off genomic surveillance efforts. Here, we conducted a genomic analysis of 23 MPV-infected patients from New York City during the early outbreak, assessing the phylogenetic relationship of these strains against publicly available MPV genomes. Additionally, we compared the genomic sequences of clinical isolates versus culture-passaged samples from a subset of samples. Phylogenetic analysis revealed that MPV genomes included in this study cluster within the B.1 lineage (Clade IIb), with some of the samples displaying further differentiation into five different sub-lineages of B.1. Mutational analysis revealed 55 non-synonymous polymorphisms throughout the genome, with some of these mutations located in critical regions required for viral multiplication, structural and assembly functions, as well as the target region for antiviral treatment. In addition, we identified a large majority of polymorphisms associated with GA > AA and TC > TT nucleotide replacements, suggesting the action of human APOBEC3 enzyme. A comparison between clinical isolates and cell culture-passaged samples failed to reveal any difference. Our results provide a first glance at the mutational landscape of early MPV-2022 (B.1) circulating strains in NYC.

Population-based survey of human monkeypox disease knowledge in the Philippines: An online cross-sectional study.

In July 2022, the human monkeypox virus was declared by the World Health Organization, a public health emergency of global concern. This study investigated the Filipinos' knowledge of monkeypox and determined the demographic variables that predicted it. Correlational and cross-sectional design adhering to STROBE guidelines. Participants were recruited conveniently through social media platforms (n=575). This study used a 21-item monkeypox knowledge survey questionnaire to collect data from July to September 2022. Logistic regression analysis was used to analyse the data. Most participants (53.74%) were above 30 years old, females (68.87%), residing in Luzon (54.96%), college graduates (61.04%), Catholics (78.61%) and employed (68%). Social media, particularly Facebook (57.91%), is the common source of monkeypox-related information (78.61%). Participants' age (>30 years old) is the only predictor of monkeypox infection knowledge (aOR: 3.13; 95%CI: 1.25-7.87, p=.015). They are three times more likely to be knowledgeable than those under 30. The findings highlight the importance of evidence-based strategies for increasing public knowledge and awareness. The government, healthcare workers and the public should adopt proactive preventive measures against human monkeypox to prevent future pandemics. No patient or public contribution has been made in this study. What problem did the study address? Assessing people's knowledge about monkeypox will help the government and healthcare workers (HCWs) create policies to prevent the spread of the virus. To the best of my knowledge, this is the first study that used a national online survey to assess Filipinos' human monkeypox knowledge. What were the main findings? Most participants had insufficient knowledge of the monkeypox infection. Participants' primary source of monkeypox infection information is social media, specifically Facebook. Participants older than 30 had higher knowledge of monkeypox infection. Where and on whom will the research have impact? Raising public awareness and knowledge about monkeypox disease prevents viral transmission in the community. HCWs (e.g., nurses, midwives, and doctors) should report monkeypox patients to appropriate health authorities. Standard and droplet precautions should be practiced and taught to the public to prevent the virus' spread. The government and HCWs should intensify monkeypox awareness programs to increase the public's knowledge and awareness of the disease. They can utilize social media platforms to disseminate correct and relevant information.

Investigation of a mpox outbreak in Central African Republic, 2021-2022

Human monkeypox virus is spreading globally, and more information is required about its epidemiological and clinical disease characteristics in endemic countries. We report the investigation of an outbreak in November 2021 in Central African Republic (CAR). The primary case, a hunter, fell ill after contact with a non-human primate at the frontier between forest and savannah. The ensuing investigation in a small nearby town concerned two families and four waves of inter-human transmission, with 14 confirmed cases, 11 suspected cases and 17 non-infected contacts, and a secondary attack rate of 59.5% (25/42). Complications were observed in 12 of the 19 (63.2%) confirmed and suspected cases with available clinical follow-up data: eight cases of bronchopneumonia, two of severe dehydration, one corneal ulcer, one abscess, two cutaneous superinfections, and six cutaneous sequelae (cheloid scars, or depigmentation). There was one death, giving a case fatality ratio of 1/25 (4.0%) for confirmed and suspected cases. This outbreak, with the largest number of confirmed cases ever described in CAR, confirms the potential severity of the disease associated with clade I monkeypox viruses, and highlights the need for rapid control over virus circulation to prevent the further national and international spread of infection.

Human Monkey pox virus in Democratic Republic of the Congo: a potential health threat?

Human Monkey pox virus in Democratic Republic of the Congo: a potential health threat?

The outbreak of the monkeypox virus in the shadow of the pandemic.

The human monkeypox virus (MPXV) was first identified in 1959. Since then, the incidence of the disease has been sporadic. The endemic regions were identified in Africa's central and western areas. However, the infection started to spread in 2017 to non-endemic regions such as North and South America, Europe, and Asia. Since May 2022, the non-endemic areas reported 62,635 till 20th September 2022. Although the monkeypox virus has a mortality of ≥ 10%, it showed only 82 mortalities worldwide in 2022. The common symptoms include chills, fever, fatigue, and skin lesions, and the complications include secondary respiratory tract infections, encephalitis, blindness, and severe diarrhea. The factors responsible for spreading the virus include improper handling and consumption of infected bushmeat, unprotected sexual intercourse, contact with an infected person, no smallpox vaccination, improper hygiene, lower diagnostic capacity, and strong travel history from the endemic regions. The therapeutic strategy is symptom-based treatment and supportive care. Antivirals and vaccines such as Tecovirimat, Brincidofovir, Cidofovir, Imvamune, and ACAM2000 have shown promising results. The primary purpose of the review is to perform an epidemiological study and investigate the pathobiology, diagnosis, prevention, treatment, and some associated complications of the monkeypox virus in 2022.

Monkeypox Awareness Among the Syrian Doctors and Medical Students: A Cross Sectional Study

Background: World Health Organization (WHO) verified 780 cases of monkeypox across 27 countries between 13 May 2022 and 2 June 2022. The World Health Organization (WHO) classified the growing worldwide monkeypox epidemic a PHEIC on July 23; the bulk of confirmed cases have been found in European locations. The purpose of this research is to assess the level of awareness toward human monkeypox virus among the Syrian medical students, general practitioners (GPs), medical residents, and specialists. Methods: We performed a cross-sectional online survey in Syria between 2 may and 8 September, 2022 to assess medical students', general practitioners', residents', and specialists' knowledge about the monkeypox virus. The utilized tool was developed with input from the World Health Organization, the Centers for Disease Control and Prevention, and cross-sectional studies conducted in Indonesia. The survey has 53 questions divided into three groups: demographic information, work-related details, and monkeypox knowledge. The time-efficient and simple snowball method of sampling was used. Version 28.0 of SPSS was used to analyze the data. Results: A total of 1257 healthcare workers and medical students throughout all of Syria's governorates took part in the research. The percentage of responders who learned anything about monkeypox in medical school was just 6.2% (n = 78). As a whole, students scored 10.23 out of a possible 15, with 11 being the adequate level for knowledge. About half of the participants (n = 700) are familiar with the term "monkeypox." As well, half of the respondents (n = 663) just learned about monkeypox during the last few days, while almost half (n = 530) only learned about it within the past month. Almost participants didn't know adequately about monkeypox. The natural host and incubation time for monkeypox were correctly identified by just 2.7% of responders and 33.3% of the whole population, respectively. 1.8% of participants gave the right response when asked about the symptoms of monkeypox. Sixty percent of the study sample think the symptoms of monkeypox and smallpox are identical. The females had higher knowledge toward monkeypox (aOR = 1.5, 95% CI = 1.26-1.80, p<0.001) than males. Respondents who are specialist doctors had higher knowledge toward monkeypox (aOR = 2.96, 95% CI = 2.24-3.92, p<0.001) than others. Conclusion: Due to the critical lack of knowledge about monkeypox among Syrian clinicians and undergraduate medical students, urgent action to solve this local issue is required. Therefore, education and awareness regarding monkeypox vaccinations are of paramount importance. In order to improve the medical community's capacity to respond to human monkeypox cases and report them into a disease surveillance system, it is crucial that doctors have a better understanding of the illness.

In silico discovery of potent inhibitors against monkeypox’s major structural proteins

Monkeypox virus (MPXV) outbreak in non-endemic countries is a worldwide public health emergency. An enveloped double-stranded DNA virus belongs to the genus Orth poxvirus. A viral zoonotic infection known as monkeypox has been a serious risk to public health, especially in Africa. However, it has recently spread to other continents, so it might soon become a worldwide problem. There is an increased risk of transmission of the virus because there is a lack of effective treatment that cures the disease. To stop the multi-country outbreak from spreading, it is important to discover effective medications urgently. The objective of the current study is to swiftly find new treatments for the monkeypox virus using advanced computational approaches. By investigating five potential MPXV targets (DNA ligase, Palmytilated Extracellular Enveloped Virus (EEV) membrane protein, Scaffold protein D13, Thymidylate Kinase, and Viral core cysteine proteinase), this research was carried out using cutting-edge computational techniques against human monkeypox virus infection. Here we present the accurate 3D structures and their binding cavities of the selected targets with higher confidence using AlphaFold 2 and SiteMap analysis. Molecular docking and MD simulation analysis revealed the top five potential lead compounds with higher binding affinity and stability toward selected targets. Binding free energy calculations and other essential dynamics analysis supports the finding. The selected lead compounds utilizing virtual screening and drug repurposing approach reported in this study are beneficial for medical scientists and experimental biologists in drug development for the treatment of human MPXV.Communicated by Ramaswamy H. Sarma

Emergence of monkeypox: a worldwide public health crisis.

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.

The monkeypox diagnosis, treatments and prevention: A review.

The world is currently dealing with a second viral outbreak, monkeypox, which has the potential to become an epidemic after the COVID-19 pandemic. People who reside in or close to forest might be exposed indirectly or at a low level, resulting in subclinical disease. However, the disease has lately emerged in shipped African wild mice in the United States. Smallpox can cause similar signs and symptoms to monkeypox, such as malaise, fever, flu-like signs, headache, distinctive rash, and back pain. Because Smallpox has been eliminated, similar symptoms in a monkeypox endemic zone should be treated cautiously. Monkeypox is transmitted to humans primarily via interaction with diseased animals. Infection through inoculation via interaction with skin or scratches and mucosal lesions on the animals is conceivable significantly once the skin barrier is disrupted by scratches, bites, or other disturbances or trauma. Even though it is clinically unclear from other pox-like infections, laboratory diagnosis is essential. There is no approved treatment for human monkeypox virus infection, however, smallpox vaccination can defend counter to the disease. Human sensitivity to monkeypox virus infection has grown after mass vaccination was discontinued in the 1980s. Infection may be prevented by reducing interaction with sick patients or animals and reducing respiratory exposure among people who are infected.

First case of mpox diagnosed in Queensland, Australia: clinical and molecular aspects.

First case of mpox diagnosed in Queensland, Australia: clinical and molecular aspects.

Molecular evolution of the human monkeypox virus.

Recently, in 2022, new cases of human monkeypox virus (hMPXV) occurred in Europe and North America. The first case was reported in Europe in May 2022, and subsequently, more than 50 000 new cases were confirmed in 100 countries. Currently, the classification of hMPXV according to the nextstrain occurs in five big clades (1A, A.1, A.2, A.1.1, and B.1).According to the resurgence of smallpox-like disease caused by hMPXV and the spread of the virus to the European and American continents, in the present study, we review and summarize the molecular evolution of the hMPXV, determining the molecular evolution of the main clades.A total of 442 hMPXV whole-genome sequenceswith available information from the country and sampling date (between October 2017 and 2022), were obtained and evaluated using the Bayesian method.The clade B.1 which is currently circulating was the most frequent (n = 415; 93.9%). The other clades presented the following frequencies: 1A (n = 13; 2.9%), A.1 (n = 10; 2.3%), A.2 (n = 3; 0.7%) and A.1.1 (n = 1; 0.2%) The overall nucleotide divergence of hMPXV was 5.590e-5. The 1A clade was detected between 2017 and 2020. A.1 was observed, and between 2019 and 2022 some A.2 sequences were detected. In 2022, the great predominance of B.1 was observed. The common ancestor of the hMPXV belongs to the clade 1A and the time to the Most Recent Common Ancestor (tMRCA) was 2017-04-04 (Highest Posterior Density 95% (HPD95%): 2017-03-09; 2017-08-04) on the West African continent. The tMRCA of A.1 was 2018-05-21 (HPD95%: 2018-05-20; 2018-07-04) with divergence of 6.885e-5 substitutions per site per year. This clade was of West African origin but was eventually detected in European countries. Also, A.2 was detected with sequences of North America and showed tMRCA of 2019-07-15 (HPD95%: 2018-11-18; 2020-02-24). A.1.1 showed tMRCA from 2021 to 06-05 (HPD95%: 2021-06-05; 2021-11-26) and this clade was detected in North America and was the precursor for the globally spreading B.1 which tMRCA was 2022-04-26 (HPD95%: 2022-02-27; 2022-04-26). hMPXV has been spread from West Africa to the United Kingdom, Israel, Singapore, the USA, Canada, Portugal, Spain, Ireland, France, Belgium, the Netherlands, Switzerland, Germany, Italy, Slovenia, Austria, the Republic Czech, Sweden, and Finland. hMPXV also reached countries such as Brazil, Mexico, Australia, and Taiwan.The common ancestor of the hMPXV belongs to the clade 1A with origin in the West African continent. Clade B.1 was responsible for the recent widespread worldwide. Immunization to prevent the spread of hMPXV is not yet available to the public, future studies should focus on the development of effective vaccines to contain the spread of this virus.

Recently Added Frameshift Mutation in Human Monkeypox Virus (hMPXV) OPG191 Gene.

Human monkeypox virus (hMPXV) has caused sporadic outbreaks intermittently across countries in recent years, with the largest outbreak in 2022. However, the underlying mechanisms remain unclear. This study searched for recently developed structural variants of the viral genome. A total of 22 hMPXV whole genome sequences were randomly selected from the National Center for Biotechnology Information GenBank sequence database for initial screening. As a result, a recent frameshift mutation based on a 2-base insertion in a coding region was identified at the 3' terminal of the OPG191 gene, which encodes MPXVgp168 (B7R) protein. With this insertion, the protein was prematurely truncated, and the last 11 amino acids were missing, with 3 alternative amino acids added. Among the hMPXV genome sequences registered in the GenBank database as of January 2023, 61 sequences lacked the 2-base insertion and 3,362 sequences were inserted. All 61 sequences without mutations were collected before 2020, whereas 3,358 (99.9%) of the 3,362 sequences with the insertion were collected during or after 2022. These findings imply that a 2-base insertion has recently emerged and has been fixed among the virus population that prevailed in 2022. In summary, a recently emerged frameshift mutation with a 2-base insertion was identified in hMPXV OPG191 gene. Although the structural and functional consequences of this mutation on virulence and infectivity are unknown, research on the possible associations between this mutation and recent hMPXV outbreaks is warranted.

Efficient Inactivation of Monkeypox Virus by World Health Organization‒Recommended Hand Rub Formulations and Alcohols.

Increasing nonzoonotic human monkeypox virus (MPXV) infections urge reevaluation of inactivation strategies. We demonstrate efficient inactivation of MPXV by 2 World Health Organization‒recommended alcohol-based hand rub solutions. When compared with other (re)emerging enveloped viruses, MPXV displayed the greatest stability. Our results support rigorous adherence to use of alcohol-based disinfectants.