Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.     

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study

ObjectivesA global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection.MethodsAll consecutive patients with a polymerase chain reaction (PCR)–confirmed monkeypox infection seen in a French referral centre were included.ResultsBetween 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients.ConclusionThe current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement.     

知往鉴今:人感染猴痘史及其非同寻常的2022年多国暴发疫情北大核心CSCD

2022年全球多个非地方性流行国家发生了人感染猴痘(human monkeypox,HMPX)暴发疫情,世界卫生组织(World Health Organization,WHO)评述此次暴发是“非同寻常的(atypical)”。要理解这一评语,就必须对猴痘及HMPX的历史有充分的认识,首先知道什么是“寻常的”暴发。因此,该文系统回顾了猴痘,尤其是HMPX的流行病学史,并结合近期WHO等组织机构,以及专家学者的观点,讨论分析此次疫情非同寻常的表现及可能原因。在为读者呈现64年来发人深省的猴痘病毒与人类互动历史的同时,也提供了HMPX暴发疫情多方面的信息和观点,有助于理解WHO等对当前疫情危险性的评估,认识暴发疫情对未来临床和公共卫生的深远影响。     

Here,There, and Everywhere: The Wide Host Range and Geographic Distribution of Zoonotic Orthopoxviruses

The global emergence of zoonotic viruses, including poxviruses, poses one of the greatest threats to human and animal health. Forty years after the eradication of smallpox, emerging zoonotic orthopoxviruses, such as monkeypox, cowpox, and vaccinia viruses continue to infect humans as well as wild and domestic animals. Currently, the geographical distribution of poxviruses in a broad range of hosts worldwide raises concerns regarding the possibility of outbreaks or viral dissemination to new geographical regions. Here, we review the global host ranges and current epidemiological understanding of zoonotic orthopoxviruses while focusing on orthopoxviruses with epidemic potential, including monkeypox, cowpox, and vaccinia viruses.     

Review of the prevalence,diagnostics, and containment measures of the current mpox outbreak

Monkeypox(mpox), is a disease from the Poxviridae family that can cause several serious medical issues. This mini-review sought to analyze the existing literature regarding the current mpox outbreak with a focus on the prevalence, diagnostics, and containment measures. Mpox cases have been reported to World Health Organization(WHO) from 85 Member States in all six WHO regions during the period of January 1, 2022, through August 3, 2022. Standardized or optimized guidelines for the clinical care ...     

Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates

Two major infectious forms of vaccinia virus (VACV) have been described: the intracellular mature virion (IMV), and the extracellular enveloped virion (EEV). Due to their stability in the environment, IMVs play a predominant role in host-to-host transmission, whereas EEVs play an important role in dissemination within the host. In a previous report, we demonstrated that mice vaccinated with VACV L1R (IMV immunogen) and A33R (EEV immunogen) were protected from a lethal poxvirus challenge. Vaccination with a combination of both genes conferred greater protection than either gene alone, suggesting that an immune response against both IMV and EEV is advantageous. Here, we report that in mice individually administered DNA vaccines with two different VACV immunogens, A27L (IMV immunogen) or B5R (EEV immunogen), failed to significantly protect; however, vaccination with a combination of both genes conferred a high level of protection. Mice were completely protected when vaccinated with a combination of four VACV genes (A27L + A33R + L1R + B5R). Rhesus macaques vaccinated with this four-gene-combination developed appropriate antibody responses to each protein. Antibody responses elicited by this vaccine cross-reacted with monkeypox virus orthologous proteins. These data indicate that a gene-based vaccine comprised of the VACV A27L + A33R + L1R + B5R genes may be a useful candidate to protect against other orthopoxviruses, including those that cause monkeypox and smallpox.     

猴痘病毒人类传播及其检测方法研究进展

猴痘是一种由猴痘病毒引起的人畜共患的新发病毒性疾病。1970年在非洲首次发现人感染猴痘病毒。2003年通过国境口岸将患病动物传入美国,并发生美国人类猴痘暴发流行。本文就近年来对猴痘病毒人间传播病例的回顾性研究及检测方法进展作一综述。