Orthopoxvirus Infections Research Articles

Diagnostic Strategies in the Era of Monkeypox Resurgence: A Comprehensive Analysis.

The resurgence of monkeypox (Mpox), an orthopoxvirus infection closely related to smallpox, presents a significant global health challenge. This study presents a comprehensive overview of Mpox, focusing on its clinical manifestations, diagnostic strategies, and testing methodologies. A thorough review of the literature and available data on Mpox, emphasizing diagnostic assays, clinical indicators, and laboratory testing, constitutes the core of this analysis. The study involves insights from Mpox patients and healthcare professionals engaged in its diagnosis and management. Contextualizing the research within the global spread of Mpox addresses the complexities associated with the diagnosis of the disease. The findings illuminate diverse Mpox diagnostic techniques, encompassing viral culture, immunological methods, serology,quantitative polymerase chain reaction (qPCR), electron microscopy, and advanced technologies such as artificial intelligence (AI) and the GeneXpert system. qPCR is highlighted as the benchmark for MPXV detection and quantification. These diagnostic advancements have significantly enhanced the precision and efficiency of Mpox diagnosis, facilitating prompt identification and treatment of infected individuals. The study underscores the critical importance of accurate and timely diagnosis, proper handling and transportation of clinical specimens, and the imperative for point-of-care (POC) testing to control the global spread of Mpox.

Analysis of aerobiological studies with orthopoxviruses by U.S. Department of Defense

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

Cellular Pathophysiology in Zoonotic Transmission of Orthopoxviruses (OPXVs) from Animal Host to Human

Orthopoxviruses (OPXVs), belonging to the Poxviridae family, are large, double-stranded DNA viruses known for their zoonotic potential and impact on human and animal health. This review explores the transmission dynamics of OPXVs from animal hosts to humans and the underlying cellular pathophysiological mechanisms. Animal hosts such as rodents, primates, and livestock are central in the ecology of OPXVs, with transmission typically occurring through direct contact or exposure to contaminated materials. Clinical manifestations in animals range from skin lesions and fever to respiratory and gastrointestinal symptoms, reflecting the diverse tissue tropism of these viruses. Humans primarily acquire OPXVs through contact with infected animals or their products, highlighting the zoonotic risk posed by these viruses. At the cellular level, OPXV infections involve complex interactions between viral proteins and host cell receptors, triggering robust immune responses characterized by cytokine release and inflammation. The viruses replicate within the cytoplasm without accessing the host cell nucleus, evading detection by nuclear sensors and exploiting cellular machinery for viral assembly. A comprehensive grasp of OPXV transmission dynamics and cellular pathophysiology is requisite to devise effective prevention and control strategies. Insights into host immune responses and viral replication mechanisms provide a foundation for antiviral drug development and vaccine strategies. This review synthesizes current knowledge on OPXV ecology, transmission, and cellular interactions, emphasizing their significance in veterinary, medical, and public health contexts.

The Re-Emergence of Mpox: Old Illness, Modern Challenges.

The Mpox virus (MPXV) is known to cause zoonotic disease in humans. The virus belongs to the genus Orthopoxvirus, of the family Poxviridae, and was first reported in monkeys in 1959 in Denmark and in humans in 1970 in the Congo. MPXV first appeared in the U.S. in 2003, re-emerged in 2017, and spread globally within a few years. Wild African rodents are thought to be the reservoir of MPXV. The exotic trade of animals and international travel can contribute to the spread of the Mpox virus. A phylogenetic analysis of MPXV revealed two distinct clades (Central African clade and West African clade). The smallpox vaccine shows cross-protection against MPXV infections in humans. Those who have not previously been exposed to Orthopoxvirus infections are more vulnerable to MPXV infections. Clinical manifestations in humans include fever, muscle pain, headache, and vesicle formation on the skin of infected individuals. Pathognomonic lesions include ballooning degenerations with Guarnieri-like inclusions in vesicular epithelial cells. Alterations in viral genome through genetic mutations might favor the re-emergence of a version of MPXV with enhanced virulence. As of November 2023, 92,783 cases and 171 deaths have been reported in 116 countries, representing a global public health concern. Here, we provide insights on the re-emergence of MPXV in humans. This review covers the origin, emergence, re-emergence, transmission, pathology, diagnosis, control measures, and immunomodulation of the virus, as well as clinical manifestations. Concerted efforts of health professionals and scientists are needed to prevent the disease and stop its transmission in vulnerable populations.

Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections

The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.

Development of a multiplex real-time PCR assay for the simultaneous detection of mpox virus and orthopoxvirus infections

Since May 2022, the multi-country outbreak of monkeypox (mpox) has raised a great concern worldwide. Early detection of mpox virus infection is recognized as an efficient way to prevent mpox transmission. Mpox specific detection methods reported up to now are based on the SNPs among mpox virus and other orthopoxviruses. We have therefore developed a real-time PCR based mpox detection method targeting mpox virus specific sequences (N3R and B18Rplus). We have also optimized an orthopoxvirus detection system which targets the highly conserved E9L and D6R genes. The mpox and orthopoxvirus real-time PCR assays have a high sensitivity (1 copy/reaction) and specificity. Mpox viral DNA and clinical samples from mpox patients are detected with the mpox detection system. Furthermore, we have established a multiplex real-time PCR detection system allowing simultaneous and efficient detection of mpox and orthopoxvirus infections.

Design and computational evaluation of a novel multi-epitope hybrid vaccine against monkeypox virus: Potential targets and immunogenicity assessment for pandemic preparedness

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential.

Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection

The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.

Age-related antibody response to Orthopoxviruses and implications for public health measures: Insights from a South Korean study

BackgroundAfter the eradication of smallpox, there have been no specific public health measures for any Orthopoxviruses (OPXVs). Therefore, it is necessary to countermeasure OPXV infections after Mpox (formerly monkeypox) occurrences, such as the latest global outbreak in 2022–2023. This study aimed to provide crucial insights for the development of effective public health policy making against mpox in populations residing in regions where the virus is not prevalent. MethodsThis study used enzyme-linked immunosorbent assays (ELISA) to examine smallpox and mpox antibodies in Koreans with three different age groups. We analyzed 56 sera obtained from a tertiary care hospital in South Korea between September 2022 and April 2023. Plasma levels of antibodies against the viral proteins of smallpox (variola cytokine response-modifying protein B) and MPXV (A29) were measured using enzyme-linked immunosorbent assays. ResultsPlasma samples from participants in their early 40 s and older exhibited higher reactivity to viral antigens than those from younger participants. Furthermore, there was a strong positive correlation in antibody positivity for the two different viruses across the sera. ConclusionsThe presence of low antibody levels in participants ˂40 years may hinder their ability to defend against OPXV. Therefore, it is imperative to implement effective public health measures to mitigate the transmission of OPXV within the community. These findings serve as fundamental information for devising strategies to combat mpox efficiently, particularly in regions where the virus is not prevalent.

Orally available nucleoside analog UMM-766 provides protection in a murine model of orthopox disease.

Although smallpox has been eradicated, other orthopoxviruses continue to be a public health concern as exemplified by the ongoing Mpox (formerly monkeypox) global outbreak. While medical countermeasures (MCMs) previously approved by the Food and Drug Administration for the treatment of smallpox have been adopted for Mpox, previously described vulnerabilities coupled with the questionable benefit of at least one of the therapeutics during the 2022 Mpox outbreak reinforce the need for identifying and developing other MCMs against orthopoxviruses. Here, we screened a panel of Merck proprietary small molecules and identified a novel nucleoside inhibitor with potent broad-spectrum antiviral activity against multiple orthopoxviruses. Efficacy testing of a 7-day dosing regimen of the orally administered nucleoside in a murine model of severe orthopoxvirus infection yielded a dose-dependent increase in survival. Treated animals had greatly reduced lesions in the lung and nasal cavity, particularly in the 10 µg/mL dosing group. Viral levels were also markedly lower in the UMM-766-treated animals. This work demonstrates that this nucleoside analog has anti-orthopoxvirus efficacy and can protect against severe disease in a murine orthopox model.IMPORTANCEThe recent monkeypox virus pandemic demonstrates that members of the orthopoxvirus, which also includes variola virus, which causes smallpox, remain a public health issue. While currently FDA-approved treatment options exist, risks that resistant strains of orthopoxviruses may arise are a great concern. Thus, continued exploration of anti-poxvirus treatments is warranted. Here, we developed a template for a high-throughput screening assay to identify anti-poxvirus small-molecule drugs. By screening available drug libraries, we identified a compound that inhibited orthopoxvirus replication in cell culture. We then showed that this drug can protect animals against severe disease. Our findings here support the use of existing drug libraries to identify orthopoxvirus-targeting drugs that may serve as human-safe products to thwart future outbreaks.

An Attenuated and Highly Immunogenic Variant of the Vaccinia Virus.

The vaccinia virus (VACV) has been used for prophylactic immunization against smallpox for many decades. However, the VACV-based vaccine had been highly reactogenic. Therefore, after the eradication of smallpox, the World Health Organization in 1980 recommended that vaccination against this infection be discontinued. As a result, there has been a rise in the occurrence of orthopoxvirus infections in humans in recent years, with the most severe being the 2022 monkeypox epidemic that reached all continents. Thus, it is crucial to address the pressing matter of developing safe and highly immunogenic vaccines for new generations to combat orthopoxvirus infections. In a previous study, we created a LAD strain by modifying the LIVP (L) VACV strain, which is used as a first-generation smallpox vaccine in Russia. This modification involved introducing mutations in the A34R gene to enhance extracellular virion production and deleting the A35R gene to counteract the antibody response to the viral infection. In this study, a strain LADA was created with an additional deletion in the DNA of the LAD strain ati gene. This ati gene directs the production of a major non-virion immunogen. The findings indicate that the LADA VACV variant exhibits lower levels of reactogenicity in BALB/c mice during intranasal infection, as compared to the original L strain. Following intradermal immunization with a 105 PFU dose, both the LAD and LADA strains were found to induce a significantly enhanced cellular immune response in mice when compared to the L strain. At the same time, the highest level of virus-specific IFN-γ producing cells for the LAD variant was detected on the 7th day post-immunization (dpi), whereas for LADA, it was observed on 14 dpi. The LAD and LADA strains induced significantly elevated levels of VACV-specific IgG compared to the original L strain, particularly between 28 and 56 dpi. The vaccinated mice were intranasally infected with the cowpox virus at a dose of 460 LD50 to assess the protective immunity at 62 dpi. The LADA virus conferred complete protection to mice, with the LAD strain providing 70% protection and the parent strain L offering protection to only 60% of the animals.

2-Aryl-1-hydroxyimidazoles possessing antiviral activity against a wide range of orthopoxviruses, including the variola virus.

Scientific interest in orthopoxvirus infections and search for new highly effective compounds possessing antiviral activity against orthopoxviruses have significantly increased as a result of worldwide mpox outbreak in 2022. The present work deals with the synthesis of new 2-arylimidazoles exhibiting in vitro activity not only against the vaccinia virus, cowpox virus and ectromelia (mousepox) virus but also against the variola virus. Among the imidazole derivatives under consideration (1-hydroxyimidazoles, 1-methoxyimidazoles, 1-benzyloxyimidazoles, and imidazole N-oxides), the most promising antiviral activity is demonstrated by 1-hydroxyimidazoles, which may exist as two prototropic tautomers. Both of these tautomers may be manifested in different crystal structures of these compounds, according to single-crystal X-ray diffraction analysis, while predominantly one of them (N-hydroxy-tautomeric form) is present in DMSO-d 6 solutions and in the gaseous state, as shown by NMR spectroscopy and quantum-chemical calculations. The leader compound 1-hydroxy-2-(4-nitrophenyl)imidazole 4a demonstrated the highest selectivity indices against the vaccinia virus (SI = 1072) and the variola virus (SI = 373).

A review of the synthetic strategies toward the antiviral drug tecovirimat.

This review provides a comprehensive analysis of synthetic routes for tecovirimat, an antiviral drug used to treat orthopoxvirus infections, including monkeypox and smallpox. We focus on the scale-up synthesis of key intermediates, including cycloheptatriene, as documented in the published literature and patent records. The review highlights the efficiency, yield, and purity of these approaches, as well as the minimization of genotoxic and in-process impurities. Furthermore, we critically evaluate the recently reported optimized industrial-scale synthesis process, highlighting its advantages and limitations, and identifying avenues for further improvement. By obtaining insights from the published literature and patent records, this review elucidates the current state of knowledge regarding key synthesis parameters influencing tecovirimat production and emphasizes the critical importance of optimizing synthesis techniques to achieve remarkable improvements in safety and environmental impact. This review serves as a valuable resource for researchers and industry professionals in the field of R&D and production of APIs, particularly in expediting the safe and efficient industrial production of tecovirimat.

Monkeypox: A Comprehensive Review of Virology, Epidemiology, Transmission, Diagnosis, Prevention, Treatment, and Artificial Intelligence Applications.

Monkeypox (Mpox), an uncommon zoonotic Orthopoxvirus, is commonly manifested by blisters on the skin and has a mortality rate of approximately 0-10%. Approximately two decades after the cessation of global smallpox vaccination, the number of confirmed cases of Mpox has been growing, making it the most common Orthopoxvirus infection. Therefore, in this narrative review, we aimed to shed light on recent advancements in the pathophysiology, transmission routes, epidemiology, manifestations, diagnosis, prevention, and treatment of Mpox, as well as the application of artificial intelligence (AI) methods for predicting this disease. The clinical manifestations of Mpox, including the onset of symptoms and dermatologic characteristics, are similar to those of the infamous smallpox, but Mpox is clinically milder. Notably, a key difference between smallpox and Mpox is the high prevalence of lymphadenopathy. Human-to-human, animal-to-human, and animal-to-animal transmission are the three main pathways of Mpox spread that must be considered for effective prevention, particularly during outbreaks. PCR testing, as the preferred method for diagnosing Mpox infection, can enhance early detection of new cases and thereby improve infection control measures. JYNNEOS and ACAM2000 are among the vaccines most commonly recommended for the prevention of Mpox. Brincidofovir, Cidofovir, and Tecovirimat are the primary treatments for Mpox cases. Similar to other viral infections, the best approach to managing Mpox is prevention. This can, in part, be achieved through measures such as reducing contact with individuals displaying symptoms, maintaining personal safety, and adhering to practices commonly used to prevent sexually transmitted infections.

Atypical presentation of mpox in Irrua environs: a case report

BackgroundMpox, previously known as monkeypox, -is an orthopoxvirus infection of the skin and previously a public health emergency of international concern. It reemerged in Nigeria over 5 years ago and has since spread to other parts of the world. This is a case report of a confirmed patient who was managed at Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria before the global surge. This report shows peculiar differences from previous patients managed at the same center in terms of the relatively prolonged eruptive phase, possible seasonal occurrence of mpox in the community, and some traditional care for mpox and skin rashes. It also corroborates previous reports of possible sexual transmission of mpox in Nigeria before the report from the global outbreak.Case presentationThe patient is a 30-year-old Nigerian male artisan with a 2-month history of raised rashes on the body that started on the genitals then involved other parts of the body. There was history of sore throat and unprotected sex with a female partner with similar rash whose other sexual history could not be ascertained. There was also history of “seasonal” rash in his village for about 7 years prior to his symptoms. Examination showed multiple vesicles and some nodules (ulcerating, healing, and healed) on the face, trunk, limbs, gluteal region, scrotum, palms, and sole, an almost circumferential penile ulcer, and lymphadenopathy. Polymerase chain reaction skin samples sent for mpox returned positive, while retroviral and coronavirus disease 2019 screenings were negative. He was managed in isolation while contact tracing in the affected community was initiated.ConclusionAtypical presentations of mpox, as managed in Irrua before the global surge, emphasize the varied spectrum of presentations (typical and atypical) in Nigeria. Therefore, there is a need for a higher index of suspicion for the uncommon presentations which will strengthen case recognition, case management, and community-based interventions as well as surveillance in the prevention and control of mpox in Irrua, its environs, Nigeria, and the world.

The Viral Protein Poly(A) Polymerase Catalytic Subunit Interacts with Guanylate-Binding Proteins 2 to Antagonize the Antiviral Ability of Targeting Ectromelia Virus.

The recent spread of the monkeypox virus among humans has heightened concerns regarding orthopoxvirus infections. Consequently, conducting a comprehensive study on the immunobiology of the monkeypox virus is imperative for the development of effective therapeutics. Ectromelia virus (ECTV) closely resembles the genetic and disease characteristics of monkeypox virus, making it a valuable research tool for studying orthopoxvirus-host interactions. Guanylate-binding proteins (GBPs), highly expressed interferon-stimulated genes (ISGs), have antagonistic effects against various intracellular pathogenic microorganisms. Our previous research has shown that GBP2 has a mild but statistically significant inhibitory effect on ECTV infection. The presence of a significant number of molecules in the poxvirus genome that encode the host immune response raises questions about whether it also includes proteins that counteract the antiviral activity of GBP2. Using IP/MS and co-IP technology, we discovered that the poly(A) polymerase catalytic subunit (PAPL) protein of ECTV is a viral regulatory molecule that interacts with GBP2. Further studies have shown that PAPL antagonizes the antiviral activity of GBP2 by reducing its protein levels. Knocking out the PAPL gene of ECTV with the CRISPR/Cas9 system significantly diminishes the replication ability of the virus, indicating the indispensable role of PAPL in the replication process of ECTV. In conclusion, our study presents preliminary evidence supporting the significance of PAPL as a virulence factor that can interact with GBP2.

ORTHOPOXVIRUSES: EPIDEMIOLOGY AND PREVENTION (REVIEW)

This review article presents information on the epidemiology of orthopoxvirus infections worldwide, their causative agents according to the classification of the International Committee on Taxonomy of Viruses of the genus Orthopoxvirus, the strains used in the development and production of vaccines, the generations of vaccines that have been developed, as well as the current situation regarding orthopoxvirus infections in the Republic of Kazakhstan

Generation of recombinant mAbs to vaccinia virus displaying high affinity and potent neutralization.

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

TECOVIRIMAT: A COMPREHENSIVE REVIEW OF NOVEL DRUG FOR MONKEYPOX DISEASE

Orthopoxvirus infections caused by pathogenic agents require therapeutic intervention. Animal models of orthopoxvirus disease are crucial for assessing the effectiveness of antiviral medications and determining the right dose and duration of treatment in the absence of disease-affected individuals. Antiviral drugs for the treatment of severe orthopoxvirus infections have been developed as a result of research on smallpox preparedness. Concerns for the public's health have been raised by the monkeypox virus, a new zoonotic orthopoxvirus that can infect humans and produce a serious, contagious illness. An infection with the monkeypox virus causes a systemic, febrile rash condition that resembles smallpox in many ways. Monkeypox virus is an emergent human pathogen. It can nonetheless result in severe morbidity and mortality in humans while being less deadly than smallpox. In this review, we have explored a new antiviral drug, Tecovirmat. This drug prevents the development of the extracellular enveloped virus required for cell-to-cell transmission. It acts by limiting the production of egress-competent enveloped virions, which are necessary for the virus's spread within the host, by decreasing the action of the orthopoxvirus VP37 envelope-wrapping protein. It was approved by US-FDA for the treatment of smallpox as per Animal Rule, which bases marketing approval on a product's effectiveness in pertinent animal models.

Monkeypox Infection, what we need to Know About

Monkeypox virus is an orthopoxvirus which was isolated for the first time in the 1950s from a group of unwell monkeys. It is in the same genus as variola that causes smallpox and vaccinia viruses. Although they are famously suspicious, there’s no clear evidence that monkeys are the primary natural reservoir of the Monkeypox virus. However, humans and monkeys are considered to be incidental hosts. Monkeypox is usually acquired by humans through contact with animal fluid or bites, nevertheless, the human-to-human infection may occur through contact with infectious skin, exposure to large respiratory droplets and/or prolonged face-to-face contact within 6 feet for more than 3 hours without appropriate protections. Interestingly, the most recent outbreak that took place in May 2022 in non-endemic places has been linked to some sexual activities through an unknown mechanism. After the discontinuation of smallpox vaccination in 1979, monkeypox was endemic in Central and West Africa with sporadic cases reported in other non-endemic countries, mostly in returning travellers from endemic areas. In 2003, the United States of America reported an outbreak of monkeypox virus from infected prairie dogs who were in contact with imported animals from Africa. The incubation period of the monkeypox virus is 6 to 13 days with a range of 5 to 21 days. The most common presenting features of monkeypox are rash, fever, lymphadenopathy, chills, and myalgias. It is usually a mild disease that might be associated with nausea and vomiting, and Most of the infected persons recover without intervention. However, more serious cases might require hospitalization and supportive care. Laboratory confirmatory tests are essential to differentiate monkeypox from fever and rash diseases. These include (i) virus isolation in mammalian cell cultures, (ii) direct electron microscopy, (iii) real-time polymerase chain reaction (PCR), and (iv) enzyme-linked immunosorbent assay (ELISA), and (v) immunofluorescent antibody assay. The public health authorities should be notified according to most states’ health regulations. Varicella, smallpox, herpes simplex infection, and other orthopoxvirus infections are the differential diagnosis for Monkeypox. Tecovirimat and brincidofovir are the approved antiviral treatment for smallpox in the United States as their activity against monkeypox are approved in animals and are expected to be effective in human infection. Cidofovir has in vitro effect against monkeypox with a particular effect against lethal monkeypox in animal models. Contact, droplet, and airborne standard precaution measures are essential for any hospitalized patient with a generalized unknown vesicular rash as monkeypox and smallpox are part of the differential diagnosis. Pre- and post-exposure smallpox vaccination prophylaxis are reasonable options for select circumstances with appropriate notifications of public health authorities. In this review, we will discuss briefly the virology, geographic distribution, diagnosis and management of monkeypox infection.