Network-Based Drug Repurposing and Genomic Analysis to Unveil Potential Therapeutics for Monkeypox Virus.

The emergence of the human monkeypox virus (MPXV) and the lack of effective medications have necessitated the exploration of various strategies to combat its infection. This study employs a network-based approach to drug discovery, utilizing the BLASTn and phylogenetic analysis to compare the MPXV genome with those of 18 related orthopoxviruses, revealing over 75% genomic similarity. Through a literature review, 160 human-host proteins linked to MPXV and its relatives were identified, leading to the construction of a human-host protein interactome. Analysis of this interactome highlighted 39 central hub proteins, which were then examined for potential drug targets. The process successfully revealed 15 targets already approved for use with medications. Additionally, the functional enrichment analysis provided insights into potential pathways and disorders connected with these targets. Four medications, namely Baricitinib, Infliximab, Adalimumab, and Etanercept, have been identified as potential candidates for repurposing to combat MPXV. In addition, the pharmacophore-based screening identified a molecule that is comparable to Baricitinib and has the potential to be effective against MPXV. The findings of the study suggest that ZINC22060520 is a promising medication for treating MPXV infection and proposes these medications as potential options for additional experimental and clinical assessment in the battle against MPXV.

MPox Skin Lesions.

Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo. Mpox was considered endemic in several African countries. A global outbreak of Mpox was first recognized in Europe in May 2022 and was declared a public health emergency of international concern on July 23, 2022. The first reported Mpox case in Indonesia was in October 2022 which was identified as an imported case, there were no new confirmed Mpox cases until 13 October 2023. Since then there were 72 cases of confirmed Mpox cases in Indonesia by the end of 2023, distributed across 6 provinces, mostly in the Java island.We present two different spectrums of Mpox skin lesions in patients living with HIV, with a positive polymerase chain reaction test for Mpox. The first patient is a 48-year-old male, who developed a maculopapular lesion, that was initially noticed on the face, the lesions were then spread to the back and hand. He identifies as men who have sex with men and living with HIV for the past 18 years. There were no lesions on the genitalia or mucosa. The second patient is a 28-year-old male, the initial symptom was fever, followed by skin lesions after around 1 week of fever. The lesion initially appears as pustules on the face and then spreads throughout the whole body, the lesions also grow larger and become pseudo-pustules and ulcers. There were also mucosal involvements in the mouth, making oral intake difficult. This patient also identified as men who have sex with men with multiple partners, HIV status was not known at the initial presentation. HIV screening was done with positive results.

Seasonal Patterns of Mpox Index Cases, Africa, 1970-2021.

Across 133 confirmed mpox zoonotic index cases reported during 1970-2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.

Socio-demographic determinants of the knowledge of Monkeypox Virus among the general public: a cross-sectional study in a Tertiary Care Center in Nepal.

BACKGROUND AND OBJECTIVE: Monkeypox virus (MPXV) is the causative agent of monkeypox's zoonotic infection and was declared a global emergency by the World Health Organization (WHO). Studies from different countries have shown insufficient knowledge among the general public on MPXV. This study aimed to assess the knowledge of the general public of Nepal on MPXV. METHODS: Three hundred people were interviewed in person in October 2022, and 282 complete responses were recorded. The questionnaire related to the knowledge of MPXV was derived from a previous study conducted among the general population of Saudi Arabia. Twenty-two questions were included that assessed the knowledge and attitude of Nepalese toward monkeypox. Statistical comparison between high and low knowledge was performed using Pearson's Chi-square test. Logistic regression models were deployed to establish the relationship between participants' knowledge and socio-demographic characteristics. RESULTS: Among the total respondents, 53.8% demonstrated high knowledge of monkeypox. People aged 18-25 years, unmarried people, and those living in urban areas had significantly higher levels of knowledge. Most respondents believed that MPXV is not a conspiracy or bioterrorism (63.1%) and agreed that it is likely to affect people's social and economic life as COVID-19 did (67.0%). The history of COVID-19 vaccination (aOR: 2.980; 95%CI: 1.227, 7.236) and the younger age (aOR: 2.975; 95%CI: 1.097, 8.069) were found to be significant determinants of the knowledge of the participants on monkeypox. CONCLUSION: We observed that most Nepalese populations had a high knowledge of monkeypox and that social media was the most valuable source of information.

Knowledge and Attitude of Human Monkeypox Viral Infection Among Healthcare Practitioners and Students in Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Human monkeypox (Mpox) is a viral zoonotic infectious disease occurs mostly in central and western Africa that can be transmitted to humans and animal. On July 2022, the World Health Organization declared the global Mpox outbreak, which considered as a huge health issue. The prevalence of Mpox in Saudi Arabia has been very low until now. AIM: This research aims to assess knowledge and attitudes of healthcare practitioners and students toward human Mpox in Saudi Arabia. METHODS:  A cross-sectional study conducted among healthcare practitioners and students in Saudi Arabia assessing knowledge, practice and attitudes towards Mpox infection. We conducted descriptive statistics for all variables. RESULTS: A total of 212 participants were included in the study. The majority of participants provided correct responses about the type of microorganisms that cause human Mpox infection and were aware about the low prevalence of the Mpox in Saudi Arabia, but they were not able to identify the correct number of cases in Saudi Arabia. About the symptoms of Mpox, participants showed good knowledge about the common symptoms like skin rash but poor knowledge about less common symptoms like lymph-node swelling. About 70% of participants were aware of the effectiveness of antiviral drugs to treat Mpox. CONCLUSION: Gaps in knowledge were detected among participants. Therefore, increasing knowledge of Mpox by providing educational courses for healthcare practitioners and healthcare students is crucial.

A Peculiar Presentation of Syphilis as a Mysterious Rash: A Dermatological Dilemma.

A renowned poet in the ancient city of Verona by the name of Girolamo Fracastoro coined the term syphilis in 1530. The stigma and shame that embodied this affliction has been time immemorial and disabling for patients. The hypothesis of the spread from the warm tropics of west and central Africa to the Iberian Peninsula accompanied by the slave trade has been a tale for centuries. Malignant syphilis is a rare skin manifestation of Treponema pallidum infection and a variant of secondary syphilis. The rash is frequently associated with HIV-infected patients, often with low cluster differentiation 4 (CD4) cell count. The authors reported a unique case involving a 46-year-old woman who presented with a one-week history of skin eruptions at various stages. Subsequent laboratory tests revealed a strong positive result for Treponema pallidum and a positive Rapid Plasma Reagin (RPR) test with a titer of 1:16. She received doxycycline because she had a history of penicillin anaphylaxis in the past. She did well, with a remarkable improvement in symptoms - a positive outcome for this catastrophic stigmatizing, rare diagnosis.

Evaluation of Monkeypox as an Unrecognized Sexually Transmitted Disease: A Rare Case of Monkeypox Infection with HIV and Syphilis Coinfection.

Monkeypox (MPX) virus is endemic in Africa. However, since May 2022, many cases have been reported worldwide in many non-endemic regions as well. The virus usually spreads from animals to humans or from humans to humans through respiratory droplets or after contact with infected lesions. In the recent outbreak of MPX, many cases did not have any travel history to endemic areas and were reported in men who have sex with men (MSM) along with the diagnosis of other sexually transmitted diseases (STDs). However, MPX is not yet considered a sexually transmitted infection (STI), even though a relationship between MPX and other STIs may exist with a possible facilitating action on their spreading. We present a similar case of MPX infection in an MSM patient with concomitant HIV and syphilis infections and no travel history to an endemic area.

Validity and Reliability of the Knowledge, Attitudes and Practices Instrument Regarding Monkey Pox in Peru.

Objective: To analyze the questionnaire of the validity and reliability of knowledge, attitudes and practices concerning Mpox. Methods: This was an instrumental, cross-sectional study. The sample consisted of 178 citizens from 3 sectors of Peru, who responded to a virtual questionnaire regarding knowledge, attitudes and practices concerning Mpox. The validity and reliability process of the questionnaire was carried out using Aiken's V, Cronbach's Alpha, McDonald's Omega and principal component analysis. Results: After expert evaluation, the questionnaire was shown to have adequate content validity for measuring knowledge, attitudes and practices concerning Mpox, each in their respective dimensions, with Aiken's V values above 0.90. For construct validity, exploratory factor analysis was used and the items were grouped into four dimensions for the level of knowledge, three dimensions for attitudes, and two for practices. With respect to the reliability analysis, the application of Cronbach's α statistic and McDonald's ω, obtained values above 0.70. Conclusion: The results of the research enabled the attainment of a questionnaire that meets the adequate psychometric characteristics in order to be applied.

Clinical and Epidemiological Interventions for Monkeypox Management in Children: A Systematic Review.

This review aims to compile the available literature on monkeypox, identify risk factors for developing the disease, and recommend effective preventative methods to reduce the number of reported cases and fatalities in children and pregnant women. In seeking out pertinent studies on monkeypox virus in children and pregnant women, we searched the literature using the databases Cochrane Library, Google Scholar, PubMed, EMBASE, Web of Science, and Scopus up to 1st February 2023. This study analyzed data from case studies of monkeypox in children and pregnant women. Clinical data and test findings of monkeypox patients less than 18 years old and pregnant women were analyzed. The Newcastle-Ottawa Scale was used to do the quality evaluation. Our record examination spanned the years 1985 to 2023 and found 17 children and five pregnant female patients treated with monkeypox in various hospitals/community centers. Zaire, Gabon, Chicago, Sierra Leone, Central African Republic, Northern DR Congo, Liberia, Cameroon, the Democratic Republic of the Congo, the United Kingdom, the Netherlands, and Florida all contributed to the 14 studies analyzed. There were no studies identified for meta-analysis of selected case studies of hospitalized children and pregnant women who were diagnosed with monkeypox. The incidence, prevalence, clinical characteristics, diagnosis, management, prevention, vaccinations, infant care, and care for expectant mothers are all discussed in this systematic review of monkeypox in children. Our research findings may provide a foundation for further focused research and the development of related recommendations or guidelines.

Adrenal Insufficiency Secondary to Monkeypox Infection: A Case Report.

Our case report confirms adrenal insufficiency following three weeks of monkeypox infection in an immunocompetent patient. As there is no specific treatment for monkeypox, steroid replacement therapy remains the cornerstone of managing adrenal insufficiency. By highlighting the importance of early identification and tracing in our case report, we contribute to the growing body of knowledge on monkeypox and emphasize the importance of identifying adrenal insufficiency and other complications like meningoencephalitis, prompting a significant early intervention that can help manage these complications effectively, potentially improving patient outcomes. In addition, understanding disease progression by tracing monkeypox cases provides valuable information on the disease's natural history, including the timeline and sequence of symptoms, associated complications, and outcomes, to avoid any small chance related to our lack of validated knowledge or incorrect assessment of the disease or the associated complications between an exposure and an effect in the target organs.

Monkeypox Virus and Other Emerging Outbreaks: An Overview and Future Perspective.

Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now become a matter of concern since cases have been reported in non-endemic countries around mid-June 2022, especially in the European region, with the transmission not related to travel. The diagnosis is made by PCR testing of the skin lesions. Even though treatment is symptomatic, antiretrovirals, such as tecovirimat, are used in severe cases. Vaccination with second and third generation vaccines is approved for prophylaxis in high risk individuals. Unfortunately, these options of treatment and prevention are only available in high income countries at the moment. This review, through a thorough literature search of articles from 2017 onward, focuses on epidemiology, clinical manifestations, challenges, treatment, prevention and control of MPX virus and how they can be corelated with other viral outbreaks including COVID-19, Acute Hepatitis of unknown origin, Measles and Dengue, to better predict and therefore prevent its transmission. The previous COVID-19 pandemic increased the disease burden on healthcare infrastructure of low-middle income countries, therefore, this recent MPX outbreak calls for a joint effort from healthcare authorities, political figures, and NGOs to combat the disease and prevent its further spread not only in high income but also in middle- and low-income countries.

ChatGPT Applications and Challenges in Controlling Monkey Pox in Pakistan.

Generative Pre-trained Transformer-based Chatbot (ChatGPT) is an emerging OpenAI application with its greater role in revolutionizing the world. ChatGPT can generate a massive amount of data by using the simple textual input. ChatGPT has its role in supporting the communities to make deciding role in healthcare sector. This paper aims to provide information about monkey pox (mpox) infection in Pakistan. Moreover, this paper analyzes the text-based information given by ChatGPT and narrates potential advantages and disadvantages about mpox infection. Spread of infection, symptoms and diagnose of mpox, control and management, and government responsibilities are major identified advantages. Findings of this paper also show some potential issues of ChatGPT AI application, which are as lack of latest data about mpox in Pakistan, reliability and performance issues, cost and resources for appropriate development and implementation of Open AI application in healthcare. Future works can be carried out to address these limitations in ChatGPT AI application.

Mpox associated with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus among people with HIV.

We report three cases of mpox (disease caused by the monkeypox virus) that developed in people with HIV co-infected with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus (PVL-MRSA), diagnosed in mid-February 2023. All three cases had preserved HIV immune status, and their mpox was mild and resolved without antiviral medications, but the trigger for their visit was the presence and history of skin and soft tissue infections. Our cases suggest that mpox is already prevalent among sexually active MSM in Tokyo, Japan. PVL-MRSA has been extremely rare in the general population of Japan, but several literatures reported widespread prevalence of PVL-MRSA among sexually active MSM-HIV. Mpox will become prevalent in the future in a population of sexually active MSM at high risk for PVL-MRSA infection, requiring an understanding of the interaction and pathogenesis of the two diseases.

Mpox (monkeypox) information on TikTok: analysis of quality and audience engagement.

BACKGROUND: Online information on mpox (monkeypox) is not well studied. We have analysed the video content, information quality, and audience engagement of mpox-related videos on TikTok. METHODS: Using a hashtag-based searching strategy, we identified 2462 mpox-related videos on TikTok from 1 January to 11 August 2022; 85 were included after exclusion criteria screening. Videos were evaluated for content on features and treatment of mpox. Video and information quality was assessed using the DISCERN instrument and the Journal of the American Medical Association (JAMA) criteria. We recorded video source, evaluation scores, and viewer engagement metrics. The Kruskal-Wallis test was used for statistical analysis and multiple linear regression for factor-association studies. RESULTS: Of the 85 videos, two assessed all content topics and highlighted 33% of all content items in clinical guidelines. The overall average score for the videos was 39.56 of 80 on the DISCERN instrument and 1.93 of 4 on the JAMA criteria. No video met all JAMA criteria. Subgroup analysis based on author identity suggested the variance in video scores by source (p<0.05 for all). Overall scores were higher for videos produced by doctors and science communicators than for those made by institutional users, nurses, and the general public. Multiple linear regression analysis showed that having people in the video (69.20, p=0.0001) and including information on treatment choices (1.15, p=0.045) were significant, independent determinants of audience engagement. CONCLUSION: Public-directed TikTok videos on mpox frequently provide incomplete, inaccurate information, highlighting the potential risks of using TikTok as a health information source.

The 2022 Monkeypox Epidemic and What Has Led to the Current State of the Disease in the US: A Systematic Review.

Monkeypox virus (MPOX) is a zoonotic disease in humans. It is similar genetically to its virus family member, smallpox. This virus has been studied since the 1970s. The virus remains endemic to the Congo and West African regions, but non-endemic spreads have been cited. The most recent non-endemic outbreak in the spring of 2022 amidst the current COVID-19 pandemic is of interest due to its impact on global medical, economic, and societal climates. This literature review aims to highlight the virology, clinical signs and symptoms, diagnosis, prevention, and treatment of MPOX and discuss the social implications of the recent 2022 outbreak. We hope this review can pinpoint important clinical pearls of the MPOX virus and its societal impacts to further promote important discussion of this virus and its disease.

Monkeypox and drug repurposing: seven potential antivirals to combat the viral disease.

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.

Designing of thiazolidinones against chicken pox, monkey pox, and hepatitis viruses: A computational approach.

Computational designing of four different series (D-G) of thiazolidinone was done starting from different amines which was further condensed with various aldehydes. These underwent in silico molecular investigations for density functional theory (DFT), molecular docking, and absorption, distribution metabolism, excretion, and toxicity (ADMET) studies. The different electrochemical parameters of the compounds are predicted using quantum mechanical modeling approach with Gaussian. The docking software was used to dock the compounds against choosing PDB file for chickenpox, human immunodeficiency, hepatitis, and monkeypox virus as 1OSN, 1VZV, 6VLK, 1RTD, 3I7H, 3TYV, 4JU3, and 4QWO, respectively. The molecular interactions were visualized with discovery studio and maximum binding affinity was observed with D8 compounds against 4QWO (-13.383 kcal/mol) while for compound D5 against 1VZV which was -12.713 kcal/mol. Swiss ADME web tool was used to assess the drug-likeness of the designed compounds under consideration, and it is concluded that these molecules had a drug-like structure with almost zero violations.

Monkeypox infection in pregnancy: a systematic review and metaanalysis.

OBJECTIVE: The World Health Organization has recently declared a monkeypox outbreak as a public health emergency of global concern. The main aim of this systematic review was to ascertain the maternal and perinatal outcomes of pregnancies complicated by monkeypox infection. DATA SOURCES: The Medline, Embase, and Cochrane databases were searched on June 25, 2022 utilizing combinations of the relevant medical subject heading terms, key words, and word variants for "monkeypox" and "pregnancy." STUDY ELIGIBILITY CRITERIA: The search and selection criteria were restricted to the English language. METHODS: The outcomes observed were miscarriage; intrauterine, neonatal, and perinatal death; preterm birth, vertical transmission, and maternal symptoms. A metaanalysis of proportions was used to analyze the data. RESULTS: Four studies were included. All the cases in the present systematic review presented with symptoms and signs of monkeypox infection. There was no case of maternal death. Miscarriage occurred in 39% of cases (95% confidence interval, 0-89.0), whereas intrauterine fetal death occurred in 23.0% (95% confidence interval, 0-74.0) of cases. The overall incidence of late fetal and perinatal loss was 77.0% (95% confidence interval, 26.0-100), whereas only 23% (95% confidence interval, 0-74.0) of the included fetuses survived to birth. The incidence of preterm birth before 37 weeks of gestation was 8.0% (95% confidence interval, 0-62.0). Vertical transmission occurred in 62.0% (95% confidence interval, 3.0-100) of cases. When stratifying the analysis according to gestational age at infection, fetal loss was found to occur in 67.0% (95% confidence interval, 9.0-99.0) of cases with first-trimester infection and in 82.0% (95% confidence interval, 17.0-100) of those with second-trimester infection. CONCLUSION: Monkeypox infection in pregnancy is associated with a high risk of perinatal loss and vertical transmission. The preliminary results from this systematic review affected by a very small number of included cases highlight the need for thorough maternal and fetal surveillance in pregnancies complicated by monkeypox infection.