ABSTRACT
Background@#As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. @*Results@#In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. @*Conclusions@#This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.
ABSTRACT
Background@#Coronavirus disease 2019 (COVID-19) outbreaks occur in hospitals in many parts of the world. In hospital settings, the possibility of airborne transmission needs to be investigated thoroughly. @*Materials and Methods@#There was a nosocomial outbreak of COVID-19 in a hematologic ward in a tertiary hospital, Seoul, Korea. We found 11 patients and guardians with COVID-19 through vigorous contact tracing and closed-circuit television monitoring. We found one patient who probably had acquired COVID-19 through airborne-transmission. We performed airflow investigation with simulation software, whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). @*Results@#Of the nine individuals with COVID-19 who had been in the hematologic ward, six stayed in one multi-patient room (Room 36), and other three stayed in different rooms (Room 1, 34, 35). Guardian in room 35 was close contact to cases in room 36, and patient in room 34 used the shared bathroom for teeth brushing 40 minutes after index used.Airflow simulation revealed that air was spread from the bathroom to the adjacent room 1 while patient in room 1 did not used the shared bathroom. Airflow was associated with poor ventilation in shared bathroom due to dysfunctioning air-exhaust, grill on the door of shared bathroom and the unintended negative pressure of adjacent room. @*Conclusion@#Transmission of SARS-CoV-2 in the hematologic ward occurred rapidly in the multi-patient room and shared bathroom settings. In addition, there was a case of possible airborne transmission due to unexpected airflow.
ABSTRACT
Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.
ABSTRACT
The most effective way to control newly emerging infectious disease, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, is to strengthen preventative or therapeutic public health strategies before the infection spreads worldwide. However, global health systems remain at the early stages in anticipating effective therapeutics or vaccines to combat the SARS-CoV-2 pandemic. While maintaining social distance is the most crucial metric to avoid spreading the virus, symptomatic therapy given to patients on the clinical manifestations helps save lives. The molecular properties of SARS-CoV-2 infection have been quickly elucidated, paving the way to therapeutics, vaccine development, and other medical interventions. Despite this progress, the detailed biomolecular mechanism of SARS-CoV-2 infection remains elusive. Given virus invasion of cells is a determining factor for virulence, understanding the viral entry process can be a mainstay in controlling newly emerged viruses. Since viral entry is mediated by selective cellular proteases or proteins associated with receptors, identification and functional analysis of these proteins could provide a way to disrupt virus propagation. This review comprehensively discusses cellular machinery necessary for SARS-CoV-2 infection. Understanding multifactorial traits of the virus entry will provide a substantial guide to facilitate antiviral drug development.
ABSTRACT
Purpose@#Neutralizing antibodies (NAbs) have been considered effective in preventing and treating viral infections. However, until now, the duration and clinical implications of antibody-mediated nature immunity in Koreans have remained unknown.Therefore, we examined NAbs levels and clinical characteristics in recovered coronavirus disease 2019 (COVID-19) patients. @*Materials and Methods@#Blood samples were collected from 143 adult patients who had been diagnosed with and had recovered from COVID-19 from February to March in 2020 at a tertiary-care university-affiliated hospital in Daegu, Korea. A plaque reduction neutralization test was conducted to analyze NAb titers. Individualized questionnaires were used to identify patient clinical information. @*Results@#The median number of days from symptom onset to the blood collection date was 109.0 (104.0; 115.0). The NAb titers ranged from 10 to 2560. The median NAb titer value was 40. Of the 143 patients, 68 (47.6%) patients had NAb titers ≥80, and 31 (21.7%) patients had NAb titers ≥160. The higher the age or disease severity, the higher the NAb titer. In univariate logistic regression, statistically significant predictors of high NAb titers (≥80) were age, myalgia, nausea or vomiting, dyspnea, and disease severity (p<0.05). Multivariable logistic regression showed that age ≥50 years (p=0.013) and moderate or higher disease severity (p<0.001) were factors associated with high NAb titers (≥80). None of the patients had reinfection of COVID-19. @*Conclusion@#All recovered patients were found to have NAbs regardless of the NAb titers maintained by natural immunity. Age and disease severity during COVID-19 infection were associated with high NAb titers.
ABSTRACT
Background@#Coronavirus disease 2019 (COVID-19) outbreaks occur in hospitals in many parts of the world. In hospital settings, the possibility of airborne transmission needs to be investigated thoroughly. @*Materials and Methods@#There was a nosocomial outbreak of COVID-19 in a hematologic ward in a tertiary hospital, Seoul, Korea. We found 11 patients and guardians with COVID-19 through vigorous contact tracing and closed-circuit television monitoring. We found one patient who probably had acquired COVID-19 through airborne-transmission. We performed airflow investigation with simulation software, whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). @*Results@#Of the nine individuals with COVID-19 who had been in the hematologic ward, six stayed in one multi-patient room (Room 36), and other three stayed in different rooms (Room 1, 34, 35). Guardian in room 35 was close contact to cases in room 36, and patient in room 34 used the shared bathroom for teeth brushing 40 minutes after index used.Airflow simulation revealed that air was spread from the bathroom to the adjacent room 1 while patient in room 1 did not used the shared bathroom. Airflow was associated with poor ventilation in shared bathroom due to dysfunctioning air-exhaust, grill on the door of shared bathroom and the unintended negative pressure of adjacent room. @*Conclusion@#Transmission of SARS-CoV-2 in the hematologic ward occurred rapidly in the multi-patient room and shared bathroom settings. In addition, there was a case of possible airborne transmission due to unexpected airflow.
ABSTRACT
Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.
ABSTRACT
The most effective way to control newly emerging infectious disease, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, is to strengthen preventative or therapeutic public health strategies before the infection spreads worldwide. However, global health systems remain at the early stages in anticipating effective therapeutics or vaccines to combat the SARS-CoV-2 pandemic. While maintaining social distance is the most crucial metric to avoid spreading the virus, symptomatic therapy given to patients on the clinical manifestations helps save lives. The molecular properties of SARS-CoV-2 infection have been quickly elucidated, paving the way to therapeutics, vaccine development, and other medical interventions. Despite this progress, the detailed biomolecular mechanism of SARS-CoV-2 infection remains elusive. Given virus invasion of cells is a determining factor for virulence, understanding the viral entry process can be a mainstay in controlling newly emerged viruses. Since viral entry is mediated by selective cellular proteases or proteins associated with receptors, identification and functional analysis of these proteins could provide a way to disrupt virus propagation. This review comprehensively discusses cellular machinery necessary for SARS-CoV-2 infection. Understanding multifactorial traits of the virus entry will provide a substantial guide to facilitate antiviral drug development.
ABSTRACT
Purpose@#Neutralizing antibodies (NAbs) have been considered effective in preventing and treating viral infections. However, until now, the duration and clinical implications of antibody-mediated nature immunity in Koreans have remained unknown.Therefore, we examined NAbs levels and clinical characteristics in recovered coronavirus disease 2019 (COVID-19) patients. @*Materials and Methods@#Blood samples were collected from 143 adult patients who had been diagnosed with and had recovered from COVID-19 from February to March in 2020 at a tertiary-care university-affiliated hospital in Daegu, Korea. A plaque reduction neutralization test was conducted to analyze NAb titers. Individualized questionnaires were used to identify patient clinical information. @*Results@#The median number of days from symptom onset to the blood collection date was 109.0 (104.0; 115.0). The NAb titers ranged from 10 to 2560. The median NAb titer value was 40. Of the 143 patients, 68 (47.6%) patients had NAb titers ≥80, and 31 (21.7%) patients had NAb titers ≥160. The higher the age or disease severity, the higher the NAb titer. In univariate logistic regression, statistically significant predictors of high NAb titers (≥80) were age, myalgia, nausea or vomiting, dyspnea, and disease severity (p<0.05). Multivariable logistic regression showed that age ≥50 years (p=0.013) and moderate or higher disease severity (p<0.001) were factors associated with high NAb titers (≥80). None of the patients had reinfection of COVID-19. @*Conclusion@#All recovered patients were found to have NAbs regardless of the NAb titers maintained by natural immunity. Age and disease severity during COVID-19 infection were associated with high NAb titers.
ABSTRACT
As of September 2020, SARS-CoV-2 has infected over 30 million people worldwide, and the death toll has now risen to 950,000. Given that Povidone-iodine (PVP-I) had consistently been showing the virucidal efficacy against various types of viruses, such as SARS-CoV, MERS-CoV, and Ebola, we conducted this study to figure out the virucidal effect against SARS-CoV-2 by using a viral plaque assay. We performed Kill-Time assays to assess the viral inactivation of SARS-CoV-2 contaminants after the application of the PVP-I product (Betadine® Throat Spray, PVP-I 0.45%). This test consisted of clean and dirty conditions and was designed to check the viral titers at a contact time of 60 seconds, which were evaluated by plaque-reduction rates in Vero cells. This PVP-I product fully achieved ≥4 log 10 reductions in viral titers under both clean and dirty conditions. This level of reduction, ≥4 log 10 (99.99%), in viral titers presented to be effective in terms of virucidal efficacy, according to the European standards, EN14476. This study revealed the virucidal efficacy of Betadine® Throat Spray against SARS-CoV-2 virus. Given that the convenience and availability of this product, we think that it may contribute to inhibit viral infection and transmissibility as an active type of personal protective equipment (PPE) by managing the hygiene of patients and medical professionals.
ABSTRACT
As of September 2020, SARS-CoV-2 has infected over 30 million people worldwide, and the death toll has now risen to 950,000. Given that Povidone-iodine (PVP-I) had consistently been showing the virucidal efficacy against various types of viruses, such as SARS-CoV, MERS-CoV, and Ebola, we conducted this study to figure out the virucidal effect against SARS-CoV-2 by using a viral plaque assay. We performed Kill-Time assays to assess the viral inactivation of SARS-CoV-2 contaminants after the application of the PVP-I product (Betadine® Throat Spray, PVP-I 0.45%). This test consisted of clean and dirty conditions and was designed to check the viral titers at a contact time of 60 seconds, which were evaluated by plaque-reduction rates in Vero cells. This PVP-I product fully achieved ≥4 log 10 reductions in viral titers under both clean and dirty conditions. This level of reduction, ≥4 log 10 (99.99%), in viral titers presented to be effective in terms of virucidal efficacy, according to the European standards, EN14476. This study revealed the virucidal efficacy of Betadine® Throat Spray against SARS-CoV-2 virus. Given that the convenience and availability of this product, we think that it may contribute to inhibit viral infection and transmissibility as an active type of personal protective equipment (PPE) by managing the hygiene of patients and medical professionals.
ABSTRACT
Pandemics affect human lives severely and globally. Experience predicts that there will be a pandemic for sure although the time is unknown. When a viral epidemic breaks out, assessing its pandemic risk is an important part of the process that characterizes genomic property, viral pathogenicity, transmission in animal model, and so forth. In this review, we intend to figure out how a pandemic may occur by looking into the past influenza pandemic events. We discuss interpretations of the experimental evidences resulted from animal model studies and extend implications of viral pandemic potentials and ingredients to emerging viral epidemics. Focusing on the pandemic potential of viral infectious diseases, we suggest what should be assessed to prevent global catastrophes from influenza virus, Middle East respiratory syndrome coronavirus, dengue and Zika viruses.
ABSTRACT
The 4a and 4b proteins of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been described for their antagonism on host innate immunity. However, unlike clustering patterns of the complete gene sequences of human and camel MERS-CoVs, the 4a and 4b protein coding regions did not constitute species-specific phylogenetic groups. Moreover, given the estimated evolutionary rates of the complete, 4a, and 4b gene sequences, the 4a and 4b proteins might be less affected by species-specific innate immune pressures. These results suggest that the 4a and 4b proteins of MERS-CoV may function against host innate immunity in a manner independent of host species and/or evolutionary clustering patterns.
Subject(s)
Humans , Camelus , Clinical Coding , Coronavirus Infections , Evolution, Molecular , Immunity, Innate , Middle East Respiratory Syndrome Coronavirus , Middle East , Open Reading Frames , Phylogeny , ZoonosesABSTRACT
Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express α- and β-defensins, which are known for their antiviral and antibacterial activities. This review describes the application of human defensins. We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents. Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons. Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models. Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the ‘defensin vaccine’ concept to prime the body with a controlled supply of human defensins. In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.