• Genomics & Informatics
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• 제19권4호
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• pp.48.1-48.10
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• 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes small envelope protein (E) that plays a major role in viral assembly, release, pathogenesis, and host inflammation. Previous studies demonstrated that pyrazine ring containing amiloride analogs inhibit this protein in different types of coronavirus including SARS-CoV-1 small envelope protein E (SARS-CoV-1 E). SARS-CoV-1 E has 93.42% sequence identity with SARS-CoV-2 E and shared a conserved domain NS3/small envelope protein (NS3_envE). Amiloride analog hexamethylene amiloride (HMA) can inhibit SARS-CoV-1 E. Therefore, we performed molecular docking and dynamics simulations to explore whether amiloride analogs are effective in inhibiting SARS-CoV-2 E. To do so, SARS-CoV-1 E and SARS-CoV-2 E proteins were taken as receptors while HMA and 3-amino-5-(azepan-1-yl)-N-(diaminomethylidene)-6-pyrimidin-5-ylpyrazine-2-carboxamide (3A5NP2C) were selected as ligands. Molecular docking simulation showed higher binding affinity scores of HMA and 3A5NP2C for SARS-CoV-2 E than SARS-CoV-1 E. Moreover, HMA and 3A5NP2C engaged more amino acids in SARS-CoV-2 E. Molecular dynamics simulation for 1 ㎲ (1,000 ns) revealed that these ligands could alter the native structure of the proteins and their flexibility. Our study suggests that suitable amiloride analogs might yield a prospective drug against coronavirus disease 2019.

• Molecules and Cells
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• 제44권9호
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• pp.680-687
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• 2021

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing.

• IMMUNE NETWORK
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• 제21권6호
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• pp.39.1-39.18
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• 2021

The high virulent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that emerged in China at the end of 2019 has generated novel coronavirus disease, coronavirus disease 2019 (COVID-19), causing a pandemic worldwide. Every country has made great efforts to struggle against SARS-CoV-2 infection, including massive vaccination, immunological patients' surveillance, and the utilization of convalescence plasma for COVID-19 therapy. These efforts are associated with the attempts to increase the titers of SARS-CoV-2 neutralizing Abs (nAbs) generated either after infection or vaccination that represent the body's immune status. As there is no standard therapy for COVID-19 yet, virus eradication will mainly depend on these nAbs contents in the body. Therefore, serological nAbs neutralization assays become a requirement for researchers and clinicians to measure nAbs titers. Different platforms have been developed to evaluate nAbs titers utilizing various epitopes sources, including neutralization assays based on the live virus, pseudovirus, and neutralization assays utilizing recombinant SARS-CoV-2 S glycoprotein receptor binding site, receptor-binding domain. As a standard neutralization assay, the plaque reduction neutralization test (PRNT) requires isolation and propagation of live pathogenic SARS-CoV-2 virus conducted in a BSL-3 containment. Hence, other surrogate neutralization assays relevant to the PRNT play important alternatives that offer better safety besides facilitating high throughput analyses. This review discusses the current neutralization assay platforms used to evaluate nAbs, their techniques, advantages, and limitations.

• Pediatric Infection and Vaccine
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• 제31권1호
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• pp.147-152
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• 2024

기저 질환 없이 평소 건강하던4세 남아에서 COVID-19와 연관된 열성 경련이 발생하였다. SARS-CoV-2 양성으로 확인되어 음압격리병동에 입원한 당일 발열과 함께 25분간 전신 간대성 발작이 있었고 산소흡입, 항경련제 투여 후 소실되었다. 말초혈액, 혈액화학, 전해질, 혈액기체분석, 급성기반응물질, 면역혈청, 특수화학 검사 결과들은 참고치 내에 있었으나, 소변검사에서 케톤이 검출되었다. 가슴X선 영상검사에서 활동성 폐병변이 관찰되지 않았고, 뇌파 검사에서 이상 소견 없었다. 뇌 자기공명영상 검사에서 뇌실질 내외의 병변은 없었다. 발작은 재발하지 않았고 입원 12병일째 퇴원하였으며 신경학적 후유증은 없었다.

• Genomics & Informatics
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• 제18권4호
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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.

• Genomics & Informatics
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• 제18권4호
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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.

• BMB Reports
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• 제53권4호
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• pp.191-205
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• 2020

The unexpected pandemic set off by the novel coronavirus 2019 (COVID-19) has caused severe panic among people worldwide. COVID-19 has created havoc, and scientists and physicians are urged to test the efficiency and safety of drugs used to treat this disease. In such a pandemic situation, various steps have been taken by the government to control and prevent the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). This pandemic situation has forced scientists to rework strategies to combat infectious diseases through drugs, treatment, and control measures. COVID-19 treatment requires both limiting viral multiplication and neutralizing tissue damage induced by an inappropriate immune reaction. Currently, various diagnostic kits to test for COVID-19 are available, and repurposing therapeutics for COVID-19 has shown to be clinically effective. As the global demand for diagnostics and therapeutics continues to rise, it is essential to rapidly develop various algorithms to successfully identify and contain the virus. This review discusses the updates on specimens/samples, recent efficient diagnostics, and therapeutic approaches to control the disease and repurposed drugs mainly focusing on chloroquine/hydroxychloroquine and convalescent plasma (CP). More research is required for further understanding of the influence of diagnostics and therapeutic approaches to develop vaccines and drugs for COVID-19.

• Journal of Preventive Medicine and Public Health
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• 제56권6호
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• pp.542-551
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• 2023

Objectives: Prospective studies on vaccination status and mortality related to coronavirus disease 2019 (COVID-19) in low-resource settings are still limited. We assessed the association between vaccination status (full, partial, or none) and in-hospital mortality among COVID-19 patients at most hospitals in Jakarta, Indonesia during the Delta predomination wave. Methods: We conducted a retrospective cohort study among hospitalized COVID-19 patients who met the study criteria (>18 years old and admitted for inpatient treatment because of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection). We linked individual-level data in the hospital admission database with vaccination records. Several socio-demographic and clinical characteristics were also analyzed. A Cox proportional hazards regression model was used to explore the association between vaccination status and in-hospital mortality in this patient group. Results: In total, 40 827 patients were included in this study. Of these, 70% were unvaccinated (n=28 543) and 19.3% (n=7882) died during hospitalization. The mean age of the patients was 49 years (range, 35-59), 53.2% were female, 22.0% had hypertension, and 14.2% were treated in the intensive care unit, and the median hospital length of stay across the group was 9 days. Our study showed that the risk of in-hospital mortality among fully and partially vaccinated patients was lower than among unvaccinated adults (adjusted hazard ratio [aHR], 0.43; 95% confidence interval [CI], 0.40 to 0.47 and aHR, 0.70; 95% CI, 0.64 to 0.77, respectively). Conclusions: Vaccinated patients had fewer severe outcomes among hospitalized adults during the Delta wave in Jakarta. These features should be carefully considered by healthcare professionals in treating adults within this patient group.

• Clinical and Experimental Vaccine Research
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• 제12권4호
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• pp.265-290
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• 2023

Rare but serious thrombotic incidents in relation to thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), have been observed since the vaccine rollout, particularly among replication-defective adenoviral vector-based severe acute respiratory syndrome coronavirus 2 vaccine recipients. Herein, we comprehensively reviewed and summarized reported studies of VITT following the coronavirus disease 2019 (COVID-19) vaccination to determine its prevalence, clinical characteristics, as well as its management. A literature search up to October 1, 2021 using PubMed and SCOPUS identified a combined total of 720 articles. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline, after screening the titles and abstracts based on the eligibility criteria, the remaining 47 full-text articles were assessed for eligibility and 29 studies were included. Findings revealed that VITT cases are strongly related to viral vector-based vaccines, which are the AstraZeneca COVID-19 vaccine (95%) and the Janssen COVID-19 vaccine (4%), with much rarer reports involving messenger RNA-based vaccines such as the Moderna COVID-19 vaccine (0.2%) and the Pfizer COVID-19 vaccine (0.2%). The most severe manifestation of VITT is cerebral venous sinus thrombosis with 317 cases (70.4%) and the earliest primary symptom in the majority of cases is headache. Intravenous immunoglobulin and non-heparin anticoagulant are the main therapeutic options for managing immune responses and thrombosis, respectively. As there is emerging knowledge on and refinement of the published guidelines regarding VITT, this review may assist the medical communities in early VITT recognition, understanding the clinical presentations, diagnostic criteria as well as its management, offering a window of opportunity to VITT patients. Further larger sample size trials could further elucidate the link and safety profile.

• Pediatric Infection and Vaccine
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• 제27권3호
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• pp.180-183
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• 2020

목적: 국내 초중고 학교 등교재개 이후 소아에서의 코로나바이러스감염증-2019 (코로나19) 사례의 감염경로를 파악하고자 하였다. 방법: 2020년 5월 1일부터 7월 12일까지 국가감염병감시체계에 신고된 3-18세 소아 청소년 코로나19 확진자의 사례조사서 및 역학조사서를 분석하였다. 결과: 2020년 5월 국내 초중고 학교 등교 재개 이후 7월 12일까지 총 127명의 소아 청소년 코로나19 확진자가 신고되었다. 그 중 59명(46%)은 가족 및 친지로부터 전파된 사례였으며 18명(14%)은 학원 및 개인교습 중 전파되었다. 8명(6%)은 다중이용 시설에서 전파되었으며 3명(2%)은 학교에서 전파된 사례였다. 결론: 코로나19 감염예방을 위한 관리체계가 사전에 마련되고 준비된 경우 학교 내 코로나19 전파는 드물게 나타났다.