Advances in peptidomimetic inhibitors of coronavirus main protease / 药学学报

Coronavirus (CoVs) is a widespread pathogen that can infect humans and animals to cause serious acute and chronic respiratory diseases. Among them, SARS-CoV broke out in 2003, MERS-CoV was discovered and spread widely in 2012, and SARS-CoV-2 emerged at the end of 2019. They all belong to β-coronavirus. Peptidomimetic inhibitors targeting coronavirus main proteases (Mpro, 3CLpro) have attracted much attention because of their broad spectrum and strong antiviral efficacy. In this review, peptidomimetic inhibitors of coronavirus main protease were classified and summarized according to the different "warheads" in design strategy. And also, the molecular structures, biological activity and design ideas of the inhibitors were analyzed and discussed, which is aimed to provide useful reference for further design and development of coronavirus inhibitors.

Potential risk of brain damage and poor developmental outcomes in children prenatally exposed to sars-cov-2: a systematic review / Risco potencial de danos cerebrais e de alterações de desenvolvimento em crianças expostas ao sars-cov-2 no período pré-natal: uma revisão sistemática

ABSTRACT Objective: To perform a systematic literature review to analyze existing data on the neurological effects of coronavirus on newborns. Data sources: We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and searched the PubMed and Embase platforms for the keywords [brain damage OR pregnancy OR developmental outcomes] and [coronavirus OR SARS-CoV-2 OR SARS-CoV OR MERS-CoV] between January 1, 2000 and June 1, 2020. Data synthesis: Twenty-three reports described the course of pregnant women exposed to SARS-CoV-2, SARS-CoV, or MERS-CoV during the gestational period, eight to SARS-CoV-2, eight to SARS-CoV, and seven to MERS-CoV. No data were found on abnormalities in brain development or on a direct link between the virus and neurological abnormalities in the human embryo, fetus, or children. Spontaneous miscarriage, stillbirth, and termination of pregnancy were some complications connected with SARS/MERS-CoV infection. SARS-CoV-2 is not currently associated with complications in the gestational period. Conclusions: The literature has no data associating exposure to coronavirus during pregnancy with brain malformations and neurodevelopmental disorders. However, despite the lack of reports, monitoring the development of children exposed to SARS-CoV-2 is essential given the risk of complications in pregnant women and the potential neuroinvasive and neurotropic properties found in previous strains.

RESUMO Objetivo: Realizar uma revisão sistemática da literatura para analisar os dados existentes sobre os efeitos neurológicos do coronavírus em recém-nascidos. Fontes de dados: Esta revisão seguiu as diretrizes dos Principais Itens para Relatar Revisões Sistemáticas e Meta-Análises (Preferred Reported Items for Systematic Review - PRISMA) e dos Protocolos dos Principais Itens para Relatar Revisões Sistemáticas e Meta-Análises (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols - PRISMA-P), pesquisando as plataformas PubMed e Embase pelas palavras-chave [brain damage (dano cerebral) OU pregnancy (gravidez) OU developmental outcomes (alterações de desenvolvimento)] e [coronavirus (coronavírus) OU SARS-CoV-2 OU SARS-CoV OU MERS-CoV] entre 1º de janeiro de 2000 e 1º de junho de 2020. Síntese dos dados: Vinte e três relatos descreveram a evolução de mulheres grávidas expostas ao SARS-CoV-2, SARS-CoV ou MERS-CoV durante o período gestacional, oito ao SARS-CoV-2, oito ao SARS-CoV e sete ao MERS-CoV. Não foram encontrados dados sobre anormalidades no desenvolvimento cerebral ou sobre uma ligação direta entre o vírus e alterações neurológicas no embrião, feto ou crianças. Abortamento espontâneo, morte fetal e interrupção da gravidez foram algumas das complicações relacionadas à infecção por SARS/MERS-CoV. Até o momento, o SARS-CoV-2 não está associado a complicações no período gestacional. Conclusões: Não há dados na literatura que associem a exposição ao coronavírus durante a gravidez com malformações cerebrais e distúrbios do neurodesenvolvimento. No entanto, apesar da falta de relatos, o monitoramento do desenvolvimento de crianças expostas ao SARS-CoV-2 é essencial devido ao risco de complicações em gestantes e às potenciais propriedades neuroinvasivas e neurotrópicas encontradas em cepas anteriores.

Emergencia de sars-cov-2. aspectos básicos sobre su origen, epidemiología, estructura y patogenia para clínicos / Emerging sars-cov-2. basic information about epidemiology, origin source, structure and pathogenicity of sars-cov-2 for clinicians

SARS-CoV-2 es el tercer coronavirus que emerge en las últimas dos décadas y produce la enfermedad denominada COVID-19 (enfermedad infecciosa por coronavirus 2019). Ha demostrado ser fácilmente transmisible entre humanos con una rápida diseminación mundial y declarada como pandemia el 11 de marzo 2020. A la fecha ha causado millones de casos y muertes, disrupción de servicios sanitarios y severas consecuencias sociales, económicas y políticas en todos los países. Los estudios filogenéticos lo relacionan con SARS-CoV presentes en murciélagos. Comparte características de patogenicidad con sus parientes más cercanos, SARS-CoV y MERS-CoV. 15 a 20% de los afectados presentan cuadros graves. A la fecha no se cuenta con antivirales efectivos ni vacunas. Para un adecuado control se hace imprescindible dilucidar aspectos epidemiológicos, moleculares y de patogenicidad. En esta revisión se presenta información básica sobre epidemiología, origen, estructura y patogenia de SARS-CoV-2. i:es

SARS-CoV-2 is the third coronavirus emerging in the last two decades producing a disease denominated COVID-19 (infectious disease by coronavirus 2019). It has demostrated to be easily transmisible between humans with a fast world wide dissemination and declared a pandemia in March 11, 2020. Up to date it has caused millions of cases, deaths, disruptions in medical services and severe social, political and economic consecuences, all around the globe. Phylogenetic studies relate it to SARS-CoV present in bats. It shares pathogenic characteristics with its close relatives, SARS-CoV and MERS-CoV. 15 to 20% of the patients develop a severe clinical course. Up to date there are no effective antiviral drugs or vaccines. For an adecuate control it is essential to learn about epidemiological, pathogenic and molecular aspects. In this review some basic information about epidemiology, origin source, structure and pathogenicity of SARS-CoV-2 is presented. i:en

¿Qué lecciones nos dejará el covid-19?: Historia de los nuevos coronavirus / What lessons will the covid-19 leave us? History of the new coronaviruses

Los coronavirus han estado presentes entre los humanos hace décadas, causando entre el 10 - 30% de los resfríos comunes en los humanos. Dos coronavirus han causado pandemias y alertas globales en las últimas décadas: SARS-CoV Y MERS-CoV. SARS-CoV-2 es el séptimo coronavirus en generar una infección en humanos, y el tercero en generar una pandemia. En este artículo, presentamos y comparamos la cronología, epidemiología y las medidas de control de cada una de las pandemias: SARS, MERS y COVID-19. (AU)

Coronaviruses have been present in humans for decades, causing 10-30% of common colds in humans. Two coronaviruses have caused global pandemics and alerts in recent decades: SARS-CoV and MERS-CoV. SARS-CoV-2 is the seventh coronavirus to generate an infection in humans, and the third to generate a pandemic. In this article, we present and compare the chronology, epidemiology, and control measures of each of the pandemics: SARS, MERS and COVID-19. (AU)

COVID-19, the novel coronavirus 2019: current updates and the future

COVID-19 is a new strain that has not been previously identified in humans. It is large, enveloped, single-stranded RNA virus. The clinical features range from the common cold to more severe diseases i.e., MERS and SARS. Incubation period ranges between 1-12.5 days (median 5-6 days). As on 07 March, 2020 total confirmed cases are 1,01,927 with 3486 deaths in 93 countries/territories/areas. The various lab tests for COVID-19 virus are NAAT, serological testing, viral sequencing and viral culture. Many aspects of this virus is still not understood. The authors in this article describe studies to know the pathogenesis as well as immunological response with use of animal methods. Authors also discuss genetic engineering, evaluation of activation and inflammatory activity of myeloid cells during pathogenic human coronavirus, etc. that can help in prevention and treatment of COVID-19 in near future.

COVID-19: The outbreak caused by a new coronavirus / COVID-19: la epidemia causada por un nuevo coronavirus

Abstract Before the severe acute respiratory syndrome outbreak in 2003, coronaviruses (CoVs) were not considered to be highly pathogenic to humans. However, it was this epidemic that highlighted this group of viruses and included them among the causative agents of emerging epidemic diseases. In addition, in 2012, another new CoV responsible for the Middle East respiratory syndrome was identified. Both infections were considered a threat to global health security. At present, the third epidemic caused by a CoV is being faced. This new CoV, called 2019-nCoV, was originated in the city of Wuhan, China, and has been linked to severe respiratory infections in humans. Thanks to the collaboration of experts worldwide, more information about this virus and its infection is reported each day, which allows modifying the recommendations for its prevention and treatment, without forgetting that the ultimate goal is to control this epidemic. In this review, the important aspects of this new coronavirus, 2019-nCoV, and its disease, COVID-19, have been summarized with the information available up to February 2020.

Resumen Previo al brote del síndrome respiratorio agudo grave de 2003, los coronavirus (CoV) no eran considerados como agentes altamente patogénicos para los humanos. Sin embargo, fue dicha epidemia la que destacó este grupo de virus y lo incluyó entre los agentes causantes de enfermedades epidémicas emergentes. Adicionalmente, en 2012 se identificó un nuevo CoV causante del síndrome respiratorio de Oriente Medio. Ambas infecciones fueron consideradas una amenaza para la seguridad sanitaria mundial. Hoy en día se presenta la tercera epidemia causada por un CoV. Este nuevo CoV, llamado 2019-nCoV, se originó en la ciudad de Wuhan, China, y ha sido relacionado con infecciones respiratorias graves en humanos. Gracias a la colaboración de expertos en todo el mundo, cada día se logra obtener más información sobre este virus y la infección que causa, lo cual permite modificar las recomendaciones para su prevención y tratamiento sin olvidar que el fin último es lograr el control de la epidemia. En esta revisión se resumen los aspectos más importantes acerca del nuevo 2019-nCoV y la enfermedad COVID-19, con la información disponible hasta febrero de 2020.

Research Progress in Coronavirus and its Therapeutic Drugs / 中国药学杂志

Beginning at the end of 2019, corona virus disease 2019(COVID-19) caused by sevare acute respiratory syndrome coronavirus(SARS-CoV-2) appeared in Wuhan, China, and spread rapidly across the country. Prior to this, there had been two outbreaks in the world that caused serious consequences by different coronaviruses: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). This article introduces the structure and classification of coronaviruses, discusses the origin, virological characteristics, and epidemiological overview of three coronaviruses-SARS-CoV, MERS-CoV, and SARS-CoV-2, and reviews the drugs that are currently on the market and are being developed to treat coronavirus infections, in order to explain the characteristics of coronavirus and provide new ideas for the prevention and control of 2019-nCoV and new coronavirus.

Highly pathogenic coronaviruses: thrusting vaccine development in the spotlight

Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused major public health crises. There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date (16/05/2020). SARS-CoV, MERS-CoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity. To date, there is no specific treatment proven effective against these viral infectious diseases. Vaccination is considered one of the most effective strategies to prevent viral infections. Therefore, the development of effective vaccines against highly pathogenic coronaviruses is essential. In this review, we will briefly describe coronavirus vaccine design targets, summarize recent advances in the development of coronavirus vaccines, and highlight current adjuvants for improving the efficacy of coronavirus vaccines.

Discovery of human coronaviruses pan-papain-like protease inhibitors using computational approaches / 药物分析学报

The papain-like protease (PLpro) is vital for the replication of coronaviruses (CoVs), as well as for escaping innate-immune responses of the host. Hence, it has emerged as an attractive antiviral drug-target. In this study, computational approaches were employed, mainly the structure-based virtual screening coupled with all-atom molecular dynamics (MD) simulations to computationally identify specific inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro, which can be further developed as potential pan-PLpro based broad-spectrum antiviral drugs. The sequence, structure, and functional con-serveness of most deadly human CoVs PLpro were explored, and it was revealed that functionally important catalytic triad residues are well conserved among SARS-CoV, SARS-CoV-2, and middle east respiratory syndrome coronavirus (MERS-CoV). The subsequent screening of a focused protease in-hibitors database composed of ～7,000 compounds resulted in the identification of three candidate compounds, ADM_13083841, LMG_15521745, and SYN_15517940. These three compounds established conserved interactions which were further explored through MD simulations, free energy calculations, and residual energy contribution estimated by MM-PB(GB)SA method. All these compounds showed stable conformation and interacted well with the active residues of SARS-CoV-2 PLpro, and showed consistent interaction profile with SARS-CoV PLpro and MERS-CoV PLpro as well. Conclusively, the re-ported SARS-CoV-2 PLpro specific compounds could serve as seeds for developing potent pan-PLpro based broad-spectrum antiviral drugs against deadly human coronaviruses. Moreover, the presented infor-mation related to binding site residual energy contribution could lead to further optimization of these compounds.

Research progress on small molecule inhibitors of coronaviruses / 药学实践杂志

Coronavirus infection seriously threatens human health. There is no specific medication or vaccine so far. In recent years, domestic and foreign researchers have developed a variety of small-molecule inhibitors against the ligand S protein, RdRp, PLpro and 3CLpro of three highly pathogenic coronavirus, SARS-CoV，MERS-CoV，SARS-CoV-2. This article reviews the characteristics of these coronaviruses, action targets, small molecule inhibitors, and structure-activity relationships.

Molecular immune pathogenesis and diagnosis of COVID-19 / 药物分析学报

Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coro-navirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.

Implicaciones hepáticas en la pandemia por COVID-19 / Liver implications during the COVID-19 Pandemic

La infección generada por el coronavirus, denominado SARS-CoV-2, llamada coronavirus disease 2019(COVID-19), surgió en China a finales de diciembre de 2019. Actualmente ha sido categorizada como una pandemia por la Organización Mundial de la Salud (OMS). Se han documentado alteraciones de pruebas hepáticas, sin embargo, los estudios se han enfocado en los efectos cardíacos, pulmonares y renales de esta infección. La alteración de pruebas hepáticas en el contexto de COVID-19 puede ser consecuencia de hepatitis viral, toxicidad farmacológica, inflamación o choque. También se considera como un marcador de pronóstico y gravedad de la enfermedad. El impacto de la infección por SARS-CoV-2 en pacientes con enfer-medad hepática preexistente o receptores de trasplante hepático no es claro, y se plantean distintas hipótesis sobre mayor o menor riesgo de enfermedad grave y de descompensación de la enfermedad de base.(AU)

The infection generated by the novel coronavirus SARS-CoV-2, named Coronavirus Disease 2019 (COVID-19) emerged late December of 2019 in China. It is currently categorized as a pandemic by the World Health Organization. Studies have focused on cardiac, pulmonary, and renal effects of this infection, but liver test abnormalities have also been documented. This alteration may be a consequence of viral hepatitis, phar-macological toxicity, inflammation, or shock. It is also considered a marker of prognosis and severity of the disease. The impact of SARS-CoV-2 infection in patients with pre-existing liver disease or liver transplant recipients is unclear, and different hypotheses exist regarding the higher or lower risk of severe disease and decompensation of the underlying disease.

Middle East respiratory syndrome in Morocco: four years of surveillance and evaluation of the management of suspected cases

Background: In early 2014, Morocco took steps to prevent the Middle East respiratory syndrome disease from entering into the country. Several facilities have been equipped to accommodate suspected cases. We aimed to report the plan prepared by Morocco to prevent the importation of this infection and to evaluate our experience in the monitoring of suspected cases.Methods: We analyze the data on the forms of surveillance witch collect demographic informations, symptoms, hospitalization, travel history, risk contacts and MERS-CoV test results.Results: Since 2014, 152 patients were addressed to the Mohammed 5 Military Teaching Hospital for suspicion of MERS-CoV. The compliance with the suspect case definition was positive in 78 cases. Of these patients, 93.6% were Moroccans. All of them came from the Middle East and 77% returned from a Hajj trip. The most reported symptoms were fever (92.3%) and cough (84.6%). The most reported underlying conditions were asthma (17.9%) and diabetes (12.8%). All of these patients were negative for RT-PCR detection of MERS-CoV.Conclusions: Moroccan pilgrims go to Hajj despite the warnings of the WHO. To date, Morocco has not reported any cases of MERS-CoV. Overall, the management plan to prevent importation and transmission of MERS-Cov is satisfactory

Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia / 医学前沿

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%-60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1-7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of < 150 × 10/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32-38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

Establishment and evaluation of receptor binding domain (RBD)-based ELISA for Middle East respiratory syndrome coronavirus (MERS-CoV) antibody detection / 中华微生物学和免疫学杂志

Objective@#To establish an indirect enzyme-linked immunosorbent assay (ELISA)and to compare the efficiency of receptor binding domain (RBD) proteins in different forms for Middle East respiratory syndrome coronavirus (MERS-CoV) antibody detection.@*Methods@#The monomeric and trimeric forms of MERS-CoV RBD were expressed in Bac-insect cells, 293T cells and ExpiCHO-S™ expression system and then purified. The purified RBD proteins were identified with native gel electrophoresis and Western blot. Then, an equal amount of each RBD protein was used as coating antigen to establish an ELISA for detecting MERS-CoV IgG titer. For comparison, the newly developed ELISA and the commercial MERS-CoV IgG antibody detection kit (Euroimmune with S1 as the coating antigen) were used to measure the MERS-CoV antibody reference panel supplied by World Health Organization (WHO).@*Results@#The purified monomeric and trimeric MERS-CoV RBD were successfully prepared using 293T cells and ExpiCHO-S™ system. RBD antigens of different forms and from different systems could recognize MERS-CoV specific antibody without having any cross reaction with the sera from healthy adults. The in-house RBD-based ELISA had good detection consistency with the Euroimmune commercial kit. The positive samples showed higher and more concentrated values based on the RBD trimer than the monomer.@*Conclusions@#Novel indirect ELISA methods based on the monomeric and trimeric forms of RBD protein were established. The trimetric form-based ELISA achieved higher detection efficiency than the one using the monomer antigen, suggesting that it could be uses as a competent alternative to the commercial kit.

Establishment and evaluation of receptor binding domain (RBD)-based ELISA for Middle East re-spiratory syndrome coronavirus (MERS-CoV) antibody detection / 中华微生物学和免疫学杂志

Objective To establish an indirect enzyme-linked immunosorbent assay (ELISA)and to compare the efficiency of receptor binding domain (RBD) proteins in different forms for Middle East re-spiratory syndrome coronavirus (MERS-CoV) antibody detection. Methods The monomeric and trimeric forms of MERS-CoV RBD were expressed in Bac-insect cells, 293T cells and ExpiCHO-STM expression sys-tem and then purified. The purified RBD proteins were identified with native gel electrophoresis and Western blot. Then, an equal amount of each RBD protein was used as coating antigen to establish an ELISA for de-tecting MERS-CoV IgG titer. For comparison, the newly developed ELISA and the commercial MERS-CoV IgG antibody detection kit (Euroimmune with S1 as the coating antigen) were used to measure the MERS-CoV antibody reference panel supplied by World Health Organization (WHO). Results The purified mon-omeric and trimeric MERS-CoV RBD were successfully prepared using 293T cells and ExpiCHO-STM system. RBD antigens of different forms and from different systems could recognize MERS-CoV specific antibody without having any cross reaction with the sera from healthy adults. The in-house RBD-based ELISA had good detection consistency with the Euroimmune commercial kit. The positive samples showed higher and more concentrated values based on the RBD trimer than the monomer. Conclusions Novel indirect ELISA methods based on the monomeric and trimeric forms of RBD protein were established. The trimetric form-based ELISA achieved higher detection efficiency than the one using the monomer antigen, suggesting that it could be uses as a competent alternative to the commercial kit.

Seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in public health workers responding to a MERS outbreak in Seoul, Republic of Korea, in 2015

@#The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in the Republic of Korea was confirmed in May 2015 after a traveller returned from the Middle East. There were 186 cases, including 38 deaths, within two months. The potential of a single MERS-confirmed patient to result in such a large MERS outbreak constitutes a serious global health concern.

An Atypical Case of Middle East Respiratory Syndrome in a Returning Traveler to Korea from Kuwait, 2018

We report a case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in a 61-year-old businessman returning from Kuwait. The patient arrived there on August 16, 2018, developed watery diarrhea on August 28 (day 0), and came back to Korea on September 7 (day 10) as his condition worsened. Upon arrival, he complained of diarrhea and weakness, but denied any respiratory symptoms, and he directly went to visit an emergency room. Chest radiography revealed interstitial infiltrates in the lungs, and he was immediately transferred to an isolation unit. Quantitative real-time PCR analysis of sputum samples taken on day 11 returned positive for MERS-CoV. No secondary MERS-CoV infection was identified among people who had close contact with him. This case underscores the importance of a high index of suspicion of MERS-CoV infection in any febrile patients who present after a trip to the Middle East.

Performance Evaluation of the PowerChek MERS (upE & ORF1a) Real-Time PCR Kit for the Detection of Middle East Respiratory Syndrome Coronavirus RNA

BACKGROUND: Molecular detection of Middle East respiratory syndrome coronavirus (MERS-CoV) using real-time reverse transcription (rRT)-PCR assays is the method of choice for diagnosis of MERS. We evaluated the performance of the PowerChek MERS (upE & ORF1a) real-time PCR Kit (PowerChek MERS assay; Kogene Biotech, Korea) a one-step rRT-PCR assay for the qualitative detection of MERS-CoV. METHODS: We evaluated PowerChek MERS assay performance in comparison with nested RT-PCR and sequencing of the RNA-dependent RNA polymerase (RdRp) and N genes. To evaluate diagnostic sensitivity and specificity, 100 clinical specimens (50 positive and 50 negative for MERS-CoV) were simultaneously tested by using the PowerChek MERS and sequencing assays. Assay performance, including limit of detection and precision, was evaluated in vitro by using MERS-CoV RNA transcripts. Analytical specificity was evaluated with a diverse collection of 16 respiratory virus–positive clinical specimens and 14 respiratory bacterial isolates. RESULTS: The 95% limits of detection of the PowerChek MERS assay for the upE and the open rading frame (ORF)1a were 16.2 copies/µL and 8.2 copies/µL, respectively. No cross-reactivity was observed. The diagnostic sensitivity and specificity of the PowerChek MERS assay were both 100% (95% confidence interval, 91.1–100%). CONCLUSIONS: The PowerChek MERS assay is a straightforward and accurate assay for detecting MERS-CoV RNA. The assay will be a useful tool for the rapid diagnosis of MERS and could prove especially important for MERS outbreak control.

Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea

Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.