• BMB Reports
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• v.56 no.12
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• pp.669-674
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• 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defense against bacterial infections through iron sequestration, and it serves as a biomarker for kidney injury. In a human protein array, we observed increased lipocalin-2 expression due to parental SARS-CoV-2 infection in the Calu-3 human lung cancer cell line. The secretion of lipocalin-2 was also elevated in response to parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha, Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV-2 and Delta variant induced lipocalin-2 expression and secretion. Additionally, the iron concentration increased in the Calu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the production and secretion of lipocalin-2, potentially resulting in a decrease in iron concentration in serum. Because the concentration of iron ions in the blood is associated with anemia, this phenomenon could contribute to developing anemia in COVID-19 patients.

• The Journal of Internal Korean Medicine
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• v.30 no.3
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• pp.571-581
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• 2009

Background : Early in November 2002, severe acute respiratory syndrome (SARS) began to spread throughout thirty-two countries around the world. A total of 5,327 cases were reported in China, including 1,755 cases in Hong Kong and 655 in Taiwan. The total number of cases reported from Canada and Singapore was more than 200. The total number of SARS cases world-wide reached 8,437 with incidences. Mortality from SARS is estimated at around 11%. Under the guidance of the World Health Organization (WHO), clinical studies on the use of integrated herbal medicine and western medicine for treating SARS were carried out in China and Hong Kong. The official report suggested that integrated treatment was more effective than western medicine alone in clinical symptoms, lung inflammation, blood oxygen saturation, immunological functions and others. Objective : To overview the treatment principle and the prescriptions according to the regimens and the stages for SARS of the reports, and further to broaden our knowledge of treatment of acute infectious diseases using natural herbal medicine. Methods : We reviewed nine of WHO SARS reports that comprehensively described the principles and methods of treatment and summarized them into eight treatment methods. We analyzed the herbal formulae on the basis of their treatment principles, evaluated them in accordance with warm disease study, listed frequently used herbs, and assessed patent prescriptions and herbal injections that were mentioned in the reports. Results and Conclusion : The reports divided the course of SARS into 3 to 6 stages such as high fever stage, fastigium stage, and convalescent stage. Frequently used herbs were Radix Scutellariae, Radix Paeoniae, Radix Astragali, Semen Armeniacae, Radix Pseudostellariae, Radix Ophiopogonis, and Fructus Schizandrae. Herbal decoctions were the primary method of treatment, while extracts or injections were secondary. Prescriptions were mainly based on the warm disease study. SARS is a viral disease caused by corona virus, and herbal medicine is proven to be effective against it. We believe that evidences and experiences from SARS cases can be a good reference to further researches on acute infectious diseases.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.123-132
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• 2023

Background: Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean Red Ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus. Methods: A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2. Results: The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect. Conclusion: The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.

• 월간산업보건
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• s.187
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• pp.4-9
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• 2003

세계보건기구(WHO)에서는 동남아시아를 중심으로 발생하기 시작했던 급성호흡기감염을 '중증급성호흡지증후군(SARS)'으로 공식 명명하고 전 세계에 경보령을 발동, 각국에서는 경계령을 발동하여 환자 발생감시체제를 가동하였다. 또한 올 겨울 SARS가 다시 유행할 것에 대비해 철저한 대비책을 세워나가야 한다는 전문가의 의견이 제시되기도 하였다. 특히 우리나라는 WHO의 SARS 위험평가 분류에 의거 저위험지역에 해당되나 상반기 사스유행지역인 중국 등과 밀접한 교류가 많은 점을 감안하여 교점지역에 준하여 의료기관 중심 SARS 감시체계를 운영하고 단계별로 감시체계를 전국 병원으로 확대하기로 하였다. 이에 편집실에서는 한동안 전 세계 초미의 관심사였던 SARS에 대해 정리해보는 기회를 갖고자 원고를 청탁하여 특별기고로 다루고자 한다.

• 월간산업보건
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• s.186
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• pp.4-16
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• 2003

세계보건기구(WHO)에서는 동남아시아를 중심으로 발생하기 시작했던 급성호흡기감염을 '중증급성호흡지증후군(SARS)'으로 공식 명명하고 전 세계에 경보령을 발동, 각국에서는 경계령을 발동하여 환자 발생감시체제를 가동하였다. 또한 올 겨울 SARS가 다시 유행할 것에 대비해 철저한 대비책을 세워나가야 한다는 전문가의 의견이 제시되기도 하였다. 특히 우리나라는 WHO의 SARS 위험평가 분류에 의거 저위험지역에 해당되나 상반기 사스유행지역인 중국 등과 밀접한 교류가 많은 점을 감안하여 교점지역에 준하여 의료기관 중심 SARS 감시체계를 운영하고 단계별로 감시체계를 전국 병원으로 확대하기로 하였다. 이에 편집실에서는 한동안 전 세계 초미의 관심사였던 SARS에 대해 정리해보는 기회를 갖고자 원고를 청탁하여 특별기고로 다루고자 한다.

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1717-1721
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• 2008

Severe acute respiratory syndrome (SARS) is a life-threatening emerging respiratory disease caused by the coronavirus, SARS-CoV. The nucleocapsid (N) protein of SARS-CoV is highly antigenic and may be a suitable candidate for diagnostic applications. We constructed truncated recombinant N proteins (N1 [1-422 aa], N2 [1-109 aa], and N3 [110-422 aa]) and determined their antigenicity by Western blotting using convalescent SARS serum. The recombinants containing N1 and N3 reacted with convalescent SARS serum in Western blotting. However, the recombinant with N2 did not. In ELISA using N1 or N3 as the antigens, positive results were observed in 10 of to (100%) SARS-CoV-positive human sera. None of 50 healthy sera gave positive results in either assay. These data indicate that the ELISA using N1 or N3 has high sensitivity and specificity. These results suggest that the middle or C-terminal region of the SARS N protein is important for eliciting antibodies against SARS-CoV during the immune response, and ELISA reactions using N1 or N3 may be a valuable tool for SARS diagnosis.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.481-491
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• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.1
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• pp.9-15
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• 2022

The angiotensin-converting enzyme 2 receptor (ACE2) appears to be widely expressed in cells in the testes, predominantly in spermatogonia, Sertoli cells, and Leydig cells, and its co-expression with transmembrane protease serine 2 (TMPRSS2) is essential for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this reason, the male reproductive system could be considered a potential target for SARS-CoV-2, as well as a possible reservoir of infection. However, to date, there is very little evidence about the presence of SARS-CoV-2 in semen and testicular samples. The aim of this paper was to review the current evidence regarding the impact of SARS-CoV-2 on male fertility and sexual health, with a particular focus on reproductive hormones, the presence of the virus in seminal fluid and testis, and its impact on fertility parameters. We found very limited evidence reporting the presence of SARS-CoV-2 in semen and testicular samples, and the impact of SARS-CoV-2 on reproductive hormones and fertility parameters is unclear. The quality of the examined studies was poor due to the small sample size and several selection biases, precluding definitive conclusions. Hence, future well-designed prospective studies are needed to assess the real impact of SARS-CoV-2 on male reproductive function.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.427-434
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• 2022

The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.

• Genomics & Informatics
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• v.21 no.1
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• pp.3.1-3.10
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• 2023

Characterization as well as prediction of the secondary and tertiary structure of hypothetical proteins from their amino acid sequences uploaded in databases by in silico approach are the critical issues in computational biology. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), which is responsible for pneumonia alike diseases, possesses a wide range of proteins of which many are still uncharacterized. The current study was conducted to reveal the physicochemical characteristics and structures of an uncharacterized protein Q6S8D9_SARS of SARS-CoV. Following the common flowchart of characterizing a hypothetical protein, several sophisticated computerized tools e.g., ExPASy Protparam, CD Search, SOPMA, PSIPRED, HHpred, etc. were employed to discover the functions and structures of Q6S8D9_SARS. After delineating the secondary and tertiary structures of the protein, some quality evaluating tools e.g., PROCHECK, ProSA-web etc. were performed to assess the structures and later the active site was identified also by CASTp v.3.0. The protein contains more negatively charged residues than positively charged residues and a high aliphatic index value which make the protein more stable. The 2D and 3D structures modeled by several bioinformatics tools ensured that the proteins had domain in it which indicated it was functional protein having the ability to trouble host antiviral inflammatory cytokine and interferon production pathways. Moreover, active site was found in the protein where ligand could bind. The study was aimed to unveil the features and structures of an uncharacterized protein of SARS-CoV which can be a therapeutic target for development of vaccines against the virus. Further research are needed to accomplish the task.