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Druggability for COVID-19: in silico discovery of potential drug compounds against nucleocapsid (N) protein of SARS-CoV-2

  • Ray, Manisha;Sarkar, Saurav;Rath, Surya Narayan
    • Genomics & Informatics
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    • v.18 no.4
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    • pp.43.1-43.13
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    • 2020
  • The coronavirus disease 2019 is a contagious disease and had caused havoc throughout the world by creating widespread mortality and morbidity. The unavailability of vaccines and proper antiviral drugs encourages the researchers to identify potential antiviral drugs to be used against the virus. The presence of RNA binding domain in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be a potential drug target, which serves multiple critical functions during the viral life cycle, especially the viral replication. Since vaccine development might take some time, the identification of a drug compound targeting viral replication might offer a solution for treatment. The study analyzed the phylogenetic relationship of N protein sequence divergence with other 49 coronavirus species and also identified the conserved regions according to protein families through conserved domain search. Good structural binding affinities of a few natural and/or synthetic phytocompounds or drugs against N protein were determined using the molecular docking approaches. The analyzed compounds presented the higher numbers of hydrogen bonds of selected chemicals supporting the drug-ability of these compounds. Among them, the established antiviral drug glycyrrhizic acid and the phytochemical theaflavin can be considered as possible drug compounds against target N protein of SARS-CoV-2 as they showed lower binding affinities. The findings of this study might lead to the development of a drug for the SARS-CoV-2 mediated disease and offer solution to treatment of SARS-CoV-2 infection.

Spike protein D614G and RdRp P323L: the SARS-CoV-2 mutations associated with severity of COVID-19

  • Biswas, Subrata K.;Mudi, Sonchita R.
    • Genomics & Informatics
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    • v.18 no.4
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    • pp.44.1-44.7
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    • 2020
  • The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from Global Initiative on Sharing Avian Influenza Data (GISAID) database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14408C>T and 23403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p < 0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group (p < 0.001). The 3037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group compared with mildly affected group, but the difference was not statistically significant (p = 0.06). We concluded that spike protein D614G and RdRp P323L mutations in SARS-CoV-2 are associated with severity of COVID-19. Further studies will be required to explore whether these mutations have any impact on the severity of disease.

Associations Between General Perceptions of COVID-19 and Posttraumatic Stress Disorder in Korean Hospital Workers: Effect Modification by Previous Middle East Respiratory Syndrome Coronavirus Experience and Occupational Type

  • Lee, Youngrong;Kim, Kwanghyun;Park, Sungjin;Jung, Sun Jae
    • Journal of Preventive Medicine and Public Health
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    • v.54 no.2
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    • pp.86-95
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    • 2021
  • Objectives: This study investigated associations between perceptions of coronavirus disease 2019 (COVID-19) and the prevalence of posttraumatic stress disorder (PTSD) in workers at hospitals designated to treat COVID-19, as well as the difference in the magnitude of these associations by occupational type and previous Middle East respiratory syndrome coronavirus (MERS-CoV) experience. Methods: The participants were workers at hospitals designated to treat COVID-19 who completed a questionnaire about their perceptions related to COVID-19, work experience during the previous MERS-CoV outbreak, and symptoms of PTSD ascertained by the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders. Participants' characteristics were compared using the chi-square test. Multivariable logistic regression was performed to evaluate the associations between perceptions and the prevalence of PTSD, stratified by occupational type and previous MERS-CoV experience. Results: Non-medical personnel showed stronger associations with PTSD than medical personnel according to general fear (odds ratio [OR], 6.67; 95% confidence interval [CI], 1.92 to 23.20), shortages of supplies (OR, 1.29; 95% CI, 1.07 to 1.56), and issue-specific fear (OR, 1.29; 95% CI, 1.05 to 1.59). Those with prior MERS-CoV quarantine experience were more prone to PTSD than those without such experience in terms of general fear (OR, 1.70; 95% CI, 1.22 to 2.37), shortages of supplies (OR, 1.24; 95% CI, 1.10 to 1.40), and issue-specific fear (OR, 1.21; 95% CI, 1.06 to 1.38). Conclusions: During the COVID-19 pandemic, non-medical personnel tended to have higher odds of being categorized as having PTSD. Workers with prior MERS-CoV experience were more susceptible than those without such experience. These findings suggest the need for timely interventions to manage human resources for a sustainable quarantine system.

High-performance computing for SARS-CoV-2 RNAs clustering: a data science-based genomics approach

  • Oujja, Anas;Abid, Mohamed Riduan;Boumhidi, Jaouad;Bourhnane, Safae;Mourhir, Asmaa;Merchant, Fatima;Benhaddou, Driss
    • Genomics & Informatics
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    • v.19 no.4
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    • pp.49.1-49.11
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    • 2021
  • Nowadays, Genomic data constitutes one of the fastest growing datasets in the world. As of 2025, it is supposed to become the fourth largest source of Big Data, and thus mandating adequate high-performance computing (HPC) platform for processing. With the latest unprecedented and unpredictable mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the research community is in crucial need for ICT tools to process SARS-CoV-2 RNA data, e.g., by classifying it (i.e., clustering) and thus assisting in tracking virus mutations and predict future ones. In this paper, we are presenting an HPC-based SARS-CoV-2 RNAs clustering tool. We are adopting a data science approach, from data collection, through analysis, to visualization. In the analysis step, we present how our clustering approach leverages on HPC and the longest common subsequence (LCS) algorithm. The approach uses the Hadoop MapReduce programming paradigm and adapts the LCS algorithm in order to efficiently compute the length of the LCS for each pair of SARS-CoV-2 RNA sequences. The latter are extracted from the U.S. National Center for Biotechnology Information (NCBI) Virus repository. The computed LCS lengths are used to measure the dissimilarities between RNA sequences in order to work out existing clusters. In addition to that, we present a comparative study of the LCS algorithm performance based on variable workloads and different numbers of Hadoop worker nodes.

A Case of Isolated Acute Pancreatitis Presenting With Epigastric Pain in an 8-Year-Old Child Infected With COVID-19 (명치 통증으로 내원한 COVID-19에 감염된 8세 소아의 단독 급성 췌장염 1례)

  • Joo Ok Jin;Se Ri Jeong;Byung Ok Kwak;Sook Min Hwang;Ky Young Cho
    • Pediatric Infection and Vaccine
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    • v.30 no.2
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    • pp.104-110
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    • 2023
  • Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mainly causes respiratory symptoms such as fever, cough, sputum, and rhinorrhea, as well as digestive symptoms such as diarrhea, vomiting, and abdominal pain in children. In this report, we describe a case of a child with a SARS-CoV-2 infection who presented with epigastric pain and was subsequently diagnosed with acute pancreatitis without any concomitant infections in other organs. The epigastric pain was relieved with goal-directed vigorous fluid therapy for acute pancreatitis for 24 hours, and the serological and radiological findings normalized after two months. Acute pancreatitis should be considered as a differential diagnosis when a child with a history of COVID-19 visits the hospital with epigastric pain.

Estimation of the SARS-CoV-2 Virus Inactivation Time Using Spectral Ultraviolet Radiation (파장별 지표 자외선 복사량을 이용한 SARS-CoV-2 바이러스 비활성화 시간 추정 연구)

  • Park, Sun Ju;Lee, Yun Gon;Park, Sang Seo
    • Atmosphere
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    • v.32 no.1
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    • pp.51-60
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    • 2022
  • Corona Virus Disease 19 pandemic (COVID-19) causes many deaths worldwide, and has enormous impacts on society and economy. The COVID-19 was caused by a new type of coronavirus (Severe Acute Respiratory Syndrome Cornonavirus 2; SARS-CoV-2), which has been found that these viruses can be effectively inactivated by ultraviolet (UV) radiation of 290~315 nm. In this study, 90% inactivation time of the SARS-CoV-2 virus was analyzed using ground observation data from Brewer spectrophotometer at Yonsei University, Seoul and simulation data from UVSPEC for the period of 2015~2017 and 2020. Based on 12:00-13:00 noon time, the shortest virus inactivation time were estimated as 13.5 minutes in June and 4.8 minutes in July/August, respectively, under all sky and clear sky conditions. In the diurnal and seasonal variations, SARS-CoV-2 could be inactivated by 90% when exposed to UV radiation within 60 minutes from 10:00 to 14:00, for the period of spring to autumn. However, in winter season, the natural prevention effect was meaningless because the intensity of UV radiation weakened, and the time required for virus inactivation increased. The spread of infectious diseases such as COVID-19 is related to various and complex interactions of several variables, but the natural inactivation of viruses by UV radiation presented in this study, especially seasonal differences, need to be considered as major variables.

Cynomolgus Macaque Model for COVID-19 Delta Variant

  • Seung Ho Baek;Hanseul Oh;Bon-Sang Koo;Green Kim;Eun-Ha Hwang;Hoyin Jung;You Jung An;Jae-Hak Park;Jung Joo Hong
    • IMMUNE NETWORK
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    • v.22 no.6
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    • pp.48.1-48.13
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    • 2022
  • With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis

  • Man Sup Kwak;Seoyeon Choi;Jiseon Kim;Hoojung Lee;In Ho Park;Jooyeon Oh;Duong Ngoc Mai;Nam-Hyuk Cho;Ki Taek Nam;Jeon-Soo Shin
    • IMMUNE NETWORK
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    • v.23 no.3
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    • pp.25.1-25.17
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    • 2023
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality. High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

Application of Antimicrobial Peptide LL-37 as an Adjuvant for Middle East Respiratory Syndrome-Coronavirus Antigen Induces an Efficient Protective Immune Response Against Viral Infection After Intranasal Immunization

  • Ju Kim;Ye Lin Yang;Yongsu Jeong;Yong-Suk Jang
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.41.1-41.16
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    • 2022
  • The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

Seroconversion rates in kidney transplant recipients following SARS-CoV-2 vaccination and its association with immunosuppressive agents: a systematic review and meta-analysis

  • Maria Riastuti Iryaningrum;Alius Cahyadi;Fachreza Aryo Damara;Ria Bandiara;Maruhum Bonar Hasiholan Marbun
    • Clinical and Experimental Vaccine Research
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    • v.12 no.1
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    • pp.13-24
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    • 2023
  • This systematic and meta-analysis aims to evaluate humoral and cellular responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine among kidney transplant recipients (KTRs). We conducted a systematic literature search across databases to evaluate seroconversion and cellular response rates in KTRs receiving SARS-CoV-2 vaccines. We extracted studies that assessed seroconversion rates described as the presence of antibody de novo positivity in KTRs following SARS-CoV-2 vaccination published up to January 23rd, 2022. We also performed meta-regression based on immunosuppression therapy used. A total of 44 studies involving 5,892 KTRs were included in this meta-analysis. The overall seroconversion rate following complete dose of vaccines was 39.2% (95% confidence interval [CI], 33.3%-45.3%) and cellular response rate was 41.6% (95% CI, 30.0%-53.6%). Meta-regression revealed that low antibody response rate was significantly associated with the high prevalence of mycophenolate mofetil/mycophenolic acid (p=0.04), belatacept (p=0.02), and antiCD25 induction therapy uses (p=0.04). Conversely, tacrolimus use was associated with higher antibody response (p=0.01). This meta-analysis suggests that postvaccination seroconversion and cellular response rates in KTRs are still low. And seroconversion rate was correlated with the type of immunosuppressive agent and induction therapy used. Additional doses of the SARS-CoV-2 vaccine for this population using a different type of vaccine are considered.