Search

We present a case of mpox recurrence in a transgender woman with AIDS. Her recurrent lesions required several courses of antiviral therapy over a 5-month period and her monkeypox viral genome was subsequently noted to have tecovirimat resistance mutations. Interestingly, she developed a robust orthopoxvirus-specific T-cell response. [ABSTRACT FROM AUTHOR]

Monkeypox virus (MPV) infection has developed into a re-emerging disease, and despite the potential of tecovirimat and cidofovir drugs, there is currently no conclusive treatment. The treatment's effectiveness and cost challenges motivate us to use In Silico approaches to seek natural compounds as candidate antiviral inhibitors. Using Maestro 11.5 in Schrodinger suite 2018, available natural molecules with validated chemical structures collected from Eximed Laboratory were subjected to molecular docking and ADMET analysis against the highly conserved A42R Profilin-like Protein of Monkeypox Virus Zaire- 96-I-16 (PDB: 4QWO) with resolution of 1.52 Å solved 3D structure. Compared to the FDA-approved Tecovirimat, molecular docking revealed that Salsoline derivatives, Genistein, Semisynthetic derivative of kojic acid, and Naringenin had strengthened affinity (-8.9 to -10 kcal/mol) to 4QWO, and the molecular dynamic's simulation confirmed their high binding stability. In support of these results, the hydrogen bond analysis indicated that the Salsoline derivative had the most robust interaction with the binding pockets of 4QWO among the four molecules. Moreover, the comparative free energy analyses using MM-PBSA revealed an average binding free energy of the complexes of Salsoline derivative, Genistein, Semisynthetic derivative of kojic acid, Naringenin, of -106.418, -46.808, -50.770, and -63.319 kJ/mol, respectively which are lower than -33.855 kJ/mol of the Tecovirimat complex. Interestingly, these results and the ADMET predictions suggest that the four compounds are promising inhibitors of 4QWO, which agrees with previous results showing their antiviral activities against other viruses. [ABSTRACT FROM AUTHOR]

Background: In the 2022-2023 global outbreak, the United States and state of Texas recorded a total of 31,277 and 3,085 confirmed monkeypox (Mpox) cases respectively as of November 2023. This study aims to investigate the demographic characteristics and risk factors of Mpox outbreak in Houston and document the epidemiologic control measures implemented with their outcomes. Methods: Houston Health Department received reports of suspected Mpox cases via electronic case reports and laboratory reports from healthcare providers within Houston. These were then investigated and reclassified as either positive or negative using DNA polymerase chain reaction tests. All the reported cases received between May 2022 and January 2023 were included in this study using convenient sampling methods. Descriptive statistics using frequency distribution was used to analyze the sociodemographic, clinical features and travel history of the cases. A two-sided Chi-squared test was used to determine association between Mpox test results and risk factors with significant level set at P < 0.05. Other infection control measures such as community engagement, health education, tracking and contact tracing, vaccination, referrals and laboratory sample logistics support were implemented by the health department. Results: Out of the total of 1,625 suspected persons investigated for Mpox, 724 (44.6%) tested positive. Among the 724 confirmed cases, male was 700 (96.7%), females 20 (2.8%), transgender male 1 (0.1%), transgender female 3 (0.4%). Age groups 30-39 years constituted 43.6%, 18-29 years 27.4%, 40-49 years 18.2%, 50-59 years was 8%. Race distribution of positive cases was Whites 43.4%, African American 38.7%, Asian 1.4%. Risk factors with P < 0.05 included male gender, age groups 30-39 years and 40-49 years, travel history to Mpox endemic areas, recent sexual contact with known or suspected Mpox cases, human immunodeficiency virus seropositivity. Identifying as gay and bisexual were also statistically significant risk factors for Mpox infection. Conclusion: The timely implementation of primary and secondary prevention measures targeted at the most at-risk populations was very effective at curtailing the spread of Mpox infection within the city of Houston. [ABSTRACT FROM AUTHOR]

Monkeypox virus, a close relative of variola virus, has significantly increased the incidence of monkeypox disease in humans, with several clinical symptoms. The sporadic spread of the disease outbreaks has resulted in the need for a comprehensive understanding of the molecular mechanisms underlying disease infection and potential therapeutic targets. Protein-protein interactions play a crucial role in various cellular processes and regulate different immune signals during virus infection. Computational algorithms have gained high significance in the prediction of potential protein interaction pairs. Here, we developed a comprehensive database called HuPoxNET (https://kaabil.net/hupoxnet/) using the state-of-the-art MERN stack technology. The database leverages two sequence-based computational models to predict strain-specific protein-protein interactions between human and monkeypox virus proteins. Furthermore, various protein annotations of the human and viral proteins such as gene ontology, KEGG pathways, subcellular localization, protein domains, and novel drug targets identified from our study are also available on the database. HuPoxNET is a user-friendly platform for the scientific community to gain more insights into the monkeypox disease infection and aid in the development of therapeutic drugs against the disease. [ABSTRACT FROM AUTHOR]

Objective: The 2022 global mpox outbreak disproportionately impacted people living with HIV. This review explores recent evidence on mpox in this group, focusing on clinical presentation, complications, treatment modalities and vaccine strategies. Recent findings: Recent studies have suggested that people with HIV diagnosed with mpox have a greater risk of proctitis and hospitalization compared with people without HIV. In addition, those with advanced immunosuppression face an elevated risk of severe mpox infection, which can lead to mortality. Comprehensive and prompt supportive care using antiretrovirals and mpox antivirals is crucial in this group. Although results from randomized clinical trials are still forthcoming, recent studies suggest that early initiation of tecovirimat can prevent disease progression in people with HIV. The non‐replicative attenuated smallpox vaccine is well tolerated and effective in preventing monkeypox virus infections in people with HIV. Further studies are needed regarding long‐term vaccine effectiveness for this population. Conclusion: Evaluating the risk of severe mpox in people living with HIV requires assessing the level of immune suppression and viral control. Universal access to vaccination is imperative to prevent the resurgence of future outbreaks. [ABSTRACT FROM AUTHOR]

Introduction To better understand the factors which influence the spread of monkeypox (mpox) infection, the patients that tested positive for mpox virus by real-time PCR in one of the main infectious diseases centers in Bucharest were analyzed in this study, amounting to one third of the confirmed cases in Romania. Methods Clinical data and laboratory tests were used to build the patient profiles. In the case of positive mpox results, next-generation sequencing of the viral genome was also performed to better comprehend the epidemiology of the infections and the evolutionary path of this virus. Results Among 47 patients with clinical suspicion of infection, 18 cases tested positive for mpox by real-time PCR (RT-PCR). Patients were mainly men who have sex with men (MSM), often coinfected with HIV-1 (half of the cases) and presenting with other sexually transmitted infections (STIs). Phylogenetic analysis was performed on 20 samples (15 patients) and indicated that mpox cases in Romania were the result of multiple importing events followed by local spread. A few sequences from European countries (Germany, Italy, France) and USA were found to be closely related to the Romanian sequences. Intra-host evolution was observed and documented in one patient with HIV-1 infection with uncontrolled viremia, showing slightly different mutation profiles in two body compartments. Conclusions This study showed that the mpox cases from Romania presented similar clinical, epidemiological and mutational features with those reported by other European countries. [ABSTRACT FROM AUTHOR]

Severe mpox has been observed in people with advanced human immunodeficiency virus (HIV). We describe clinical outcomes of 13 patients with advanced HIV (CD4 <200 cells/μL), severe mpox, and multiorgan involvement. Despite extended tecovirimat courses and additional agents, including vaccinia immune globulin, cidofovir, and brincidofovir, this group experienced prolonged hospitalizations and high mortality. [ABSTRACT FROM AUTHOR]

Monkeypox virus (MPV) infection has developed into a re-emerging disease, and despite the potential of tecovirimat and cidofovir drugs, there is currently no conclusive treatment. The treatment’s effectiveness and cost challenges motivate us to use In Silico approaches to seek natural compounds as candidate antiviral inhibitors. Using Maestro 11.5 in Schrodinger suite 2018, available natural molecules with validated chemical structures collected from Eximed Laboratory were subjected to molecular docking and ADMET analysis against the highly conserved A42R Profilin-like Protein of Monkeypox Virus Zaire-96-I-16 (PDB: 4QWO) with resolution of 1.52 Å solved 3D structure. Compared to the FDA-approved Tecovirimat, molecular docking revealed that Salsoline derivatives, Genistein, Semisynthetic derivative of kojic acid, and Naringenin had strengthened affinity (−8.9 to −10 kcal/mol) to 4QWO, and the molecular dynamic’s simulation confirmed their high binding stability. In support of these results, the hydrogen bond analysis indicated that the Salsoline derivative had the most robust interaction with the binding pockets of 4QWO among the four molecules. Moreover, the comparative free energy analyses using MM-PBSA revealed an average binding free energy of the complexes of Salsoline derivative, Genistein, Semisynthetic derivative of kojic acid, Naringenin, of −106.418, −46.808, −50.770, and −63.319 kJ/mol, respectively which are lower than −33.855 kJ/mol of the Tecovirimat complex. Interestingly, these results and the ADMET predictions suggest that the four compounds are promising inhibitors of 4QWO, which agrees with previous results showing their antiviral activities against other viruses.

Mpox has recently re-emerged as a global entity of concern. We report one of the first pediatric cases in the United States and provide updated recommendations relevant to infection control and prevention measures of those in close contact with mpox.

The 2022 monkeypox outbreak, caused by the zoonotic monkeypox virus, has spread across 6 World Health Organization regions (the Americas, Africa, Europe, Eastern Mediterranean, Western Pacific, and South-East Asia) and was declared a public health emergency of international concern on July 23, 2022. The global situation is especially concerning given the atypically high rate of person-to-person transmission, which suggests viral evolution to an established human pathogen. Pregnant women are at heightened risk of vertical transmission of the monkeypox virus because of immune vulnerability and natural depletion of population immunity to smallpox among reproductive-age women, and because orthopoxviral cell entry mechanisms can overcome the typically viral-resistant syncytiotrophoblast barrier within the placenta. Data on pregnancy outcomes following monkeypox infection are scarce but include reports of miscarriage, intrauterine demise, preterm birth, and congenital infection. This article forecasts the issues that maternity units might face and proposes guidelines to protect the health of pregnant women and fetuses exposed to the monkeypox virus. We review the pathophysiology and clinical features of monkeypox infection and discuss the obstetrical implications of the unusually high prevalence of anogenital lesions. We describe the use of real-time polymerase chain reaction tests from mucocutaneous and oropharyngeal sites to confirm infection, and share an algorithm for the antenatal management of pregnant women with monkeypox virus exposure. On the basis of the best available knowledge from prenatal orthopoxvirus infections, we discuss the sonographic features of congenital monkeypox and the role of invasive testing in establishing fetal infection. We suggest a protocol for cesarean delivery to avoid the horizontal transmission of the monkeypox virus at birth and address the controversy of mother-infant separation in the postpartum period. Obstetrical concerns related to antiviral therapy with tecovirimat and vaccinia immune globulin are highlighted, including the risks of heart rate-corrected QT-interval prolongation, inaccuracies in blood glucose monitoring, and the predisposition to iatrogenic venous thromboembolism. The possibility of monkeypox vaccine hesitancy during pregnancy is discussed, and strategies are offered to mitigate these risks. Finally, we conclude with a research proposal to address knowledge gaps related to the impact of monkeypox infection on maternal, fetal, and neonatal health.

The Los Angeles County Department of Public Health established a surveillance system to identify complicated (advanced human immunodeficiency virus [HIV] or hospitalized) mpox cases. From 1 August to 30 November 2022, we identified 1581 mpox cases, of which 134 (8.5%) were complicated. A subset of 8 cases did not recover after either initiating or completing a course of oral tecovirimat. All 8 patients were HIV positive and had advanced HIV (CD4 count <200 cells/μL). We identified 8 distinct mutations previously associated with tecovirimat resistance in specimens collected from 6 patients. Ongoing surveillance of viral evolution requires close coordination between health departments and frontline providers. [ABSTRACT FROM AUTHOR]

The binding site of tecovirimat (inhibitor of the p37 orthopox membrane protein) is determined by molecular modeling methods (docking and dynamics). It is shown that tecovirimat (or ST-246) is bonded in the region of the H(N)KD phospholipase domain, thus forming a series of intermolecular contacts with N312 and K314 key amino acid residues. This binding site can be considered as a possible location for other small molecules with a pharmacophore profile similar to tecovirimat. [ABSTRACT FROM AUTHOR]

The ocular manifestations of Monkeypox virus (Mpox) infection remain incompletely characterized. Our goal is to present a case series of non-healing corneal ulcers with associated uveitis caused by Mpox infection as well as management recommendations for Mpox-related ophthalmic disease (MPXROD). Retrospective case series. Two male patients with recent hospitalization for systemic Mpox infection presented with non-healing corneal ulcer associated with anterior uveitis and severe IOP elevation. Despite initiation of conservative medical treatment including corticosteroid treatment for uveitis, in both cases, there was clinical progression with enlarging cornea lesions. Both cases received oral tecovirimat with complete healing of the corneal lesion. Corneal ulcer and anterior uveitis are rare complications of Mpox infection. Although Mpox disease is generally anticipated to be self-limited, tecovirimat may be an effective intervention in poorly healing Mpox keratitis. Corticosteroids should be used with caution in Mpox uveitis, as they might lead to worsening infection. [ABSTRACT FROM AUTHOR]

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]

Human immunodeficiency virus (HIV)–associated immunosuppression may increase the risk of hospitalization with mpox. Among persons diagnosed with mpox in the state of Georgia, we characterized the association between hospitalization with mpox and HIV status. People with HIV and a CD4 count <350 cells/mm3 or who were not engaged in HIV care had an increased risk of hospitalization. [ABSTRACT FROM AUTHOR]

To gauge the safety and utility of extended tecovirimat/cidofovir for severe mpox, here we report our experience caring for 4 patients with mpox and advanced human immunodeficiency virus (HIV) at the Hospitals of the University of Pennsylvania during the 2022 global outbreak. Three patients had recurrent courses complicated by superinfections, coinfections and insufficient nutrition/housing, requiring extended tecovirimat (5–16 weeks) and cidofovir (1–12 doses) with probenecid and fluids. At follow-up, patients had undetectable HIV RNA on antiretrovirals, improved ulcers and stable renal function on antivirals. Serology guided cessation for one 7-month cidofovir course. Overall findings support a comprehensive approach of prolonged tecovirimat/cidofovir with antiretrovirals for severe mpox, while addressing social factors. [ABSTRACT FROM AUTHOR]

Background We conducted a multicentric national study (SEIMC-CEME-22), to describe the clinical and epidemiological profile of the mpox outbreak in Spain, including the management of the disease. Methods This was a retrospective national observational study conducted by Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) and Foundation SEIMC-GESIDA. We included patients with a confirmed mpox diagnosis before 13 July 2022, and attended at the Spanish health network (the early phase of the outbreak). Epidemiological, clinical, and therapeutic data were collected. Results Of a total of 1472 patients from 52 centers included, 99% of them were cisgender men, mostly middle-aged, and 98.6% were residents in Spain. The main suspected route of transmission was sexual exposure, primarily among MSM. Occupational exposure was reported in 6 patients. Immunosuppression was present in 40% of patients, mainly due to human immunodeficiency virus (HIV). Only 6.5% of patients had been vaccinated against orthopoxvirus. Virus sequencing was performed in 147 patients (all B.1 lineage). Rash was the most frequent symptom (95.7%), followed by fever (48.2%), adenopathies (44.4%) myalgias (20.7%), proctitis (17%), and headache (14.7%). Simultaneously diagnosed sexually transmitted infections included syphilis (n = 129), gonococcal infection (n = 91), HIV (n = 67), chlamydia (n = 56), hepatitis B (n = 14), and hepatitis C (n = 11). No therapy was used in 479 patients (33%). Symptomatic therapies and antibiotics were used in 50% of cases. The most used therapy regimens were systemic corticoids (90 patients), tecovirimat (6 patients), and cidofovir (13 patients). Smallpox immunoglobulins were used in 1 patient. Fifty-eight patients were hospitalized, and 1 patient died. Conclusions Mpox outbreak in Spain affected primarily middle-aged men who were sexually active and showed a high rate of HIV infection. A range of heterogeneous therapeutics options was performed. [ABSTRACT FROM AUTHOR]

Background Data on tecovirimat effectiveness for human mpox are limited. We conducted a retrospective cross-sectional interview-based study to identify associations between tecovirimat treatment and the mpox clinical course. Methods Using public health surveillance data from King County, Washington, we recruited and interviewed persons diagnosed with mpox during May–October 2022. We calculated descriptive statistics on demographics, vaccination status, comorbidities, and symptoms including 3 self-reported dates (symptom onset, first date of symptom improvement, and illness resolution). We used multivariable linear regression, stratified by illness severity, to evaluate the association of tecovirimat treatment with time to symptom improvement and time to illness resolution. We compared individuals who did not receive tecovirimat to participants who started tecovirimat early (≤5 days from symptom onset) and late (>5 days and ≤28 days from symptom onset) in their illness. Results Of 465 individuals diagnosed with mpox, 115 (25%) participated in this study. Eighty participants (70%) received tecovirimat and 43 (37%) initiated tecovirimat early. Sixty-eight (59%) reported severe symptoms during their illness, including proctitis (n = 38 [33%]), rectal bleeding (n = 27 [24%]), or severe pain (n = 24 [21%]). In the multivariable analysis, early tecovirimat was associated with shorter time to symptom improvement (−5.5 days, P =.04) among participants with severe illness but not among those with nonsevere illness (0.9 day, P =.66). Early tecovirimat was not associated with faster illness resolution, regardless of severity. Conclusions Our small study suggests that early tecovirimat initiation may hasten subjective symptomatic improvement in people with severe mpox. Larger randomized trials are needed to evaluate this finding. [ABSTRACT FROM AUTHOR]

Following the worldwide surge in mpox (monkeypox) in 2022, cases have persisted in Asia, including South Korea, and sexual contact is presumed as the predominant mode of transmission, with a discernible surge in prevalence among immunocompromised patients. Drugs such as tecovirimat can result in drug‐resistant mutations, presenting obstacles to treatment. This study aimed to ascertain the presence of tecovirimat‐related resistant mutations through genomic analysis of the monkeypox virus isolated from a reported case involving prolonged viral shedding in South Korea. Here, tecovirimat‐resistant mutations, previously identified in the B.1 clade, were observed in the B.1.3 clade, predominant in South Korea. These mutations exhibited diverse patterns across different samples from the same patient and reflected the varied distribution of viral subpopulations in different anatomical regions. The A290V and A288P mutant strains we isolated hold promise for elucidating these mechanisms, enabling a comprehensive analysis of viral pathogenesis, replication strategies, and host interactions. Our findings imply that acquired drug‐resistant mutations, may present a challenge to individual patient treatment. Moreover, they have the potential to give rise to transmitted drug‐resistant mutations, thereby imposing a burden on the public health system. Consequently, the meticulous genomic surveillance among immunocompromised patients, conducted in this research, assumes paramount importance. [ABSTRACT FROM AUTHOR]

Monkeypox virus, a close relative of variola virus, has significantly increased the incidence of monkeypox disease in humans, with several clinical symptoms. The sporadic spread of the disease outbreaks has resulted in the need for a comprehensive understanding of the molecular mechanisms underlying disease infection and potential therapeutic targets. Protein–protein interactions play a crucial role in various cellular processes and regulate different immune signals during virus infection. Computational algorithms have gained high significance in the prediction of potential protein interaction pairs. Here, we developed a comprehensive database called HuPoxNET (https://kaabil.net/hupoxnet/) using the state-of-the-art MERN stack technology. The database leverages two sequence-based computational models to predict strain-specific protein–protein interactions between human and monkeypox virus proteins. Furthermore, various protein annotations of the human and viral proteins such as gene ontology, KEGG pathways, subcellular localization, protein domains, and novel drug targets identified from our study are also available on the database. HuPoxNET is a user-friendly platform for the scientific community to gain more insights into the monkeypox disease infection and aid in the development of therapeutic drugs against the disease.

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (

Background Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce. Methods We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation. Results Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75–45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0–47.9) and 22.4 (16.6–29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0–12.1) and 0 (0–0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P >.05). Conclusions MPXV DNA detectability varies by specimen type and persists for over 3–4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study. [ABSTRACT FROM AUTHOR]

Monkeypox (mpox), a virus belonging to the orthopoxvirus family, can cause a zoonotic infectious disease with morbidity and cosmetic complications. Therefore, effective antiviral drugs with appropriate safety profiles are important for the treatment of patients with mpox. To date, there is no FDA‐approved drug for the treatment of mpox. However, tecovirimat, brincidofovir, and cidofovir are the candidate therapies for the management of mpox. Given the safety concerns following the use of these medications, we aimed to review evidence on the clinical considerations of mpox antiviral medications that will be useful to guide clinicians in the treatment approach. Based on the current evidence, tecovirimat has favorable clinical efficacy, safety, and side effect profile and it can be considered as first‐line treatment for mpox. [ABSTRACT FROM AUTHOR]

This article delineates the systematic identification, synthesis, and impurity control methods used during the manufacturing process development of tecovirimat, an antiviral drug that treats monkeypox. Critical impurities were synthesized, and their chemical structure was confirmed through NMR analysis, GC, and HPLC mass spectrometry. The results established a thorough approach to identify, address, and control impurities to produce high-quality tecovirimat drug substance in accordance with International Conference on Harmonization (ICH)-compliant standards. This study is the first of its kind to evaluate both process and genotoxic impurities in tecovirimat, demonstrating effective control measures during commercial sample investigations and scaling up to a 60-kg batch size. The findings highlight the importance of critical impurity characterization and control in pharmaceutical development and production to ensure the safety and efficacy of the final product.

Background. On 23 July 2022, the World Health Organization declared a Public Health Emergency of International Concern. Monkeypox is a zoonotic viral disease caused by the monkeypox virus that is transmitted from animals to humans or from human to human. To date, treatment for human monkeypox is mostly symptomatic, as there is no specific standard antiviral treatment. Persons with severe symptoms and signs, immunocompromised patients, children younger than 8 years, and pregnant individuals should be considered for specific antiviral treatment. Objective. This study aims to assess effectiveness of antiviral drugs in treatment of human monkeypox. Methodology. Published clinical trials and cohort studies on the role of antivirals in the management of human monkeypox that were identified through a comprehensive search of electronic databases up to April 1, 2023. The patients included were children and adults confirmed with monkeypox. The diagnosis was based on PCR or clinical symptoms. The intervention was antivirals administration in human monkeypox patients, versus supportive treatment/placebo. Outcome measured include the duration of monkeypox until recovery, need for hospitalization, and ICU admission. Results. We included four completed studies with 195 participants assessing the safety, pharmacokinetics, and efficacy of antiviral treatments for human monkeypox compared to placebo. Three studies investigated Tecovirimat (st-246), and one investigated Brincidofovir. Both drugs were safe, tolerable, and effective with no serious adverse effects. The other 5 studies were not completed and are ongoing. Conclusion. There are currently no approved antivirals for the treatment of monkeypox; some medications could be authorized for outbreak use and are now under investigation, such as Tecovirimat, Cidofovir, and Brincidofovir.

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.

We assessed tecovirimat treatment equity for 3,740 mpox patients in New York, New York, USA, during the 2022 mpox emergency; 32.4% received tecovirimat. Treatment rates by race/ethnicity were 38.8% (White), 31.3% (Black/African American), 31.0% (Hispanic/Latino), and 30.1% (Asian/Pacific Islander/other). Future public health emergency responses must prioritize institutional and structural racism mitigation.

Cardiac involvement, such as myocarditis and pericarditis, can be a severe complication of monkeypox virus (mpox) infection and could be related to other co-infections with cardiac involvement. Tecovirimat is an antiviral specifically designed to inhibit smallpox infection diffusion and approved by the FDA for other Orthopoxvirus infections; its efficacy in mpox-infected patients is not well established.We present the case of a cardiac complication during mpox infection in a previously undiagnosed Lyme disease in a 42-year-old man living with HIV.Two days after the typical maculopapular rash, the patient reported a rise in body temperature up to 39 °C, chest pain without irradiation, and shortness of breath. We found an increase in troponin level, a slight reduction in ejection fraction, and grade 2 AV block (Mobitz 1 and 2) with frequent sinus pauses (the longest of 10.1 s). Given the suspicion of myopericarditis with cardiac conduction system involvement, the patient was admitted to the Intermediate Care Unit for continuous monitoring and further evaluation. Treatment included Ibuprofen 600 mg every 12 hours (bid) and colchicine 1 mg once daily for anti-inflammatory purposes. Concomitantly, treatment with tecovirimat was started at 600 mg bid for a total of 14 days. Cardiac MRI with gadolinium showed mild interstitial edema and pericardial enhancement. However, despite the clinical and laboratory resolution of the acute phase, bradycardia with episodes of AV block persisted at follow-up, suggesting the possibility of an additional etiology. Thus, the patient was investigated for Lyme disease because high-degree AV block is the most common presentation of Lyme carditis. Serological results evidenced a previous Borrelia burgdorferi senso latu. We decided to start treatment with doxycycline 100 mg every 12h, even pending the uncertainty of the role of a previous Lyme disease in determining the cardiac rhythm disturbances. At the evaluation on day 44, the patient was systemically well, and after cardiologist consultation, pace-maker implantation was not deemed indicated.This case underscores the importance of considering alternative causes of carditis when the clinical picture remains unclear or persists after the acute phase.

Background Human mpox is a viral disease caused by an Orthopoxvirus, human mpox virus (hMPXV), typically causing fever and a rash. Mpox has historically been endemic to parts of Central and West Africa, with small numbers of imported cases reported elsewhere, but starting May 2022 an unprecedented global outbreak caused by clade IIb hMPXV was reported outside traditionally endemic countries. This prompted the initiation of MOSAIC, a cohort study implemented in Europe and Asia that aims to describe clinical and virologic outcomes of PCR-confirmed hMPXV disease, including those who receive antiviral therapy. The focus of this article, however, is on describing the study protocol itself with implementation process and operational challenges. Methods MOSAIC recruits participants of any age with laboratory-confirmed mpox disease who provide informed consent. Participants enrol in the cohort for a total of six months. Blood, lesion and throat samples are collected at several timepoints from the day of diagnosis or the first day of treatment (Day 1) until Day 28 for PCR detection of hMPXV. Clinical data are collected by clinicians and participants (via a self-completion questionnaire) for six months to characterize the signs and symptoms associated with the illness, as well as short- and more long-term outcomes. Discussion The design and prompt implementation of clinical research response is key in addressing emerging outbreaks. MOSAIC began enrolment within two months of the start of the international mpox epidemic. Enrolment has been stopped and the last follow-up visits are expected in January 2024. ICTRP registration EU CT number: 2022-501132-42-00 (22/06/2022)

Background The 2022 global mpox outbreak was notable for transmission between persons outside of travel and zoonotic exposures and primarily through intimate contact. An understanding of the presentation of mpox in people with human immunodeficiency virus (HIV) and other immunocompromising conditions and knowledge of the efficacy of tecovirimat continue to evolve. Methods This retrospective study describes clinical features and outcomes of persons with mpox who received tecovirimat. Data were obtained via medical record review of patients prescribed tecovirimat in a health system in New York City during the height of the outbreak in 2022. Results One hundred thirty people received tecovirimat between 1 July and 1 October 2022. People with HIV (n = 80) experienced similar rates of recovery, bacterial superinfections, and hospitalization compared to patients without immunocompromising conditions. Individuals determined to be severely immunocompromised (n = 14) had a higher risk of hospitalization than those without severe immunocompromise (cohort inclusive of those with well-controlled HIV, excluding those without virologic suppression, n = 101): 50% versus 9% (P <.001). Hospitalized patients (n = 18 [13% of total]) were primarily admitted for bacterial superinfections (44.4%), with a median hospital stay of 4 days. Of those who completed follow-up (n = 85 [66%]), 97% had recovery of lesions at time of posttreatment assessment. Tecovirimat was well tolerated; there were no reported severe adverse events attributed to therapy. Conclusions There were no significant differences in outcomes between people with HIV when evaluated as a whole and patients without immunocompromising conditions. However, mpox infection was associated with higher rates of hospitalization in those with severe immunocompromise, including patients with HIV/AIDS. Treatment with tecovirimat was well tolerated. Key Points: In our mpox cohort, people with HIV had similar rates of recovery and complications as those without HIV or other immunocompromising conditions. Severe immunocompromise was associated with a higher hospitalization rate. Tecovirimat was well tolerated, with minimal side effects. [ABSTRACT FROM AUTHOR]

As of 29 August 2023, a total of 89,596 confirmed cases of Mpox (monkeypox) have been documented across 114 countries worldwide, with 157 reported fatalities. The Mpox outbreak that transpired in 2022 predominantly affected young men who have sex with men (MSM). While most cases exhibited a mild clinical course, individuals with compromised immune systems, particularly those living with HIV infection and possessing a CD4 count below 200 cells/mm3, experienced a more severe clinical trajectory marked by heightened morbidity and mortality. The approach to managing Mpox is primarily symptomatic and supportive. However, in instances characterized by severe or complicated manifestations, the utilization of antiviral medications becomes necessary. Despite tecovirimat's lack of official approval by the FDA for treating Mpox in humans, a wealth of positive clinical experiences exists, pending the outcomes of ongoing clinical trials. Brincidofovir and cidofovir have also been administered in select cases due to the unavailability of tecovirimat. Within the scope of this narrative review, our objective was to delve into the clinical attributes of Mpox and explore observational studies that shed light on the utilization of these antiviral agents. [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]

Background: In May 2022, a multi-national mpox outbreak was reported in several non-endemic countries. The only licensed treatment for mpox in the European Union is the orally available small molecule tecovirimat, which in Orthopox viruses inhibits the function of a major envelope protein required for the production of extracellular virus. Methods: We identified presumably all patients with mpox that were treated with tecovirimat in Germany between the onset of the outbreak in May 2022 and March 2023 and obtained demographic and clinical characteristics by standardized case report forms. Results: A total of twelve patients with mpox were treated with tecovirimat in Germany in the study period. All but one patient identified as men who have sex with men (MSM) who were most likely infected with mpox virus (MPXV) through sexual contact. Eight of them were people living with HIV (PLWH), one of whom was newly diagnosed with HIV at the time of mpox, and four had CD4+ counts below 200/µl. Criteria for treatment with tecovirimat included severe immunosuppression, severe generalized and/or protracted symptoms, a high or increasing number of lesions, and the type and location of lesions (e.g., facial or oral soft tissue involvement, imminent epiglottitis, or tonsillar swelling). Patients were treated with tecovirimat for between six and 28 days. Therapy was generally well-tolerated, and all patients showed clinical resolution. Conclusions: In this cohort of twelve patients with severe mpox, treatment with tecovirimat was well tolerated and all individuals showed clinical improvement. [ABSTRACT FROM AUTHOR]

Purpose of Review: The 2022 global mpox outbreak is a significant public health challenge. This review provides a summary of recent advancements in mpox phylogenetics, epidemiology, transmission, clinical presentation, treatment, and vaccination. Recent Findings: The 2022 outbreak saw a shift in epidemiology, with human-to-human transmission, particularly among men who have sex with men (MSM), becoming the primary mode of spread. Among IIb.B.1 sequences, there is evidence for an emerging human-adapted monkeypox virus (MPXV). Antiviral treatments like tecovirimat have shown promise in severe cases. Two doses of the non-replicative 3rd generation vaccine MVA-BN provide better protection than a single dose. Summary: This outbreak underscores the importance of global surveillance, prompt response, and effective vaccination strategies in managing emerging infectious diseases. Efforts to destigmatize the disease and increase awareness among high-risk populations are vital in curbing transmission. Continued research and international collaboration are essential for understanding the MPXV and improving preparedness for future outbreaks. [ABSTRACT FROM AUTHOR]

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Since May 2022, there have been nearly 87,000 documented cases of mpox worldwide, with 119 deaths. Pharmacological interventions for mpox include the MVA-BN smallpox vaccine, tecovirimat, cidofovir, its pro-drug brincidofovir, and vaccinia immune globulin intravenous (VIGIV). The literature search and information gathering for this review included the PubMed database focusing on mpox and monkeypox, in combination with tecovirimat, brincidofovir, cidofovir, VIGIV, and smallpox vaccine. WHO.int, CDC.gov, FDA.gov, and ClinicalTrials.gov websites were accessed for the most recent information on the mpox outbreak. Mechanisms for deployment and access to treatment including expanded access, emergency use, and clinical trials will be discussed. Treatment outcomes with safety data will be presented. The vaccine as a preventive measure, along with numerous treatment options, largely controlled the outbreak, although deployment of each could be improved upon to hasten and broaden access. More widespread coverage by the vaccine is necessary to prevent future resurgence of mpox. Tecovirimat has emerged as a safe frontline treatment for mpox, while brincidofovir use has been limited by safety concerns. VIGIV and cidofovir should be reserved for the most severe cases in which other options are not fully effective. [ABSTRACT FROM AUTHOR]