• Molecules and Cells
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• v.21 no.2
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• pp.186-191
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• 2006

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), a distant member of the Group 2 coronaviruses, has recently been identified as the etiological agent of severe acute respiratory syndrome (SARS). The genome of SARS-CoV contains four structural genes that are homologous to genes found in other coronaviruses, as well as six subgroup-specific open reading frames (ORFs). ORF3 encodes a predicted 154-amino-acid protein that lacks similarity to any known protein, and is designated 3b in this article. We reported previously that SARS-CoV 3b is predominantly localized in the nucleolus, and induces G0/G1 arrest and apoptosis in transfected cells. In this study, we show that SARS-CoV 3b fused with EGFP at its N- or C- terminus co-localized with a mitochondriaspecific marker in some transfected cells. Mutation analysis of SARS-CoV 3b revealed that the domain spanning amino acids 80 to 138 was essential for its mitochondria localization. These results provide new directions for studies of the role of SARS-CoV 3b protein in SARS pathogenesis.

• 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.

• Clinical and Experimental Reproductive Medicine
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• v.51 no.2
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• pp.151-157
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• 2024

Objective: People vaccinated with the coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) mRNA vaccine have reported experiencing various adverse effects. For instance, reproductive-age women have presented with complaints of abnormal uterine bleeding or menstrual cycle changes. We speculated that differences in basal sex hormone levels before and after vaccination may be present in women who experienced irregular bleeding or menstrual cycle changes; thus, this study aimed to investigate the differences in basal sex hormone levels of women before and after two doses of SARS-CoV-2 mRNA vaccination. Methods: This retrospective study included patients who received SARS-CoV-2 mRNA vaccines between January 2021 and February 2022 at a single center. In an outpatient setting, patients were queried regarding their menstrual cycle, the date of SARS-CoV-2 mRNA vaccination, vaccination type, and vaccination side effects. Differences in basal hormone levels (menstrual cycle days 2-3, follicle-stimulating hormone [FSH], luteinizing hormone [LH], and estradiol) before and after vaccination were compared. Results: Among the 326 patients, patients with no laboratory records of the hormones were excluded. The median time interval between SARS-CoV-2 mRNA vaccination and the laboratory test day was 79 days (interquartile range, 44 to 127). A comparative analysis of these hormones before and after vaccination revealed no significant differences. Subgroup analyses based on age and reported adverse events also found no statistically significant differences. Conclusion: This study showed no significant differences in basal hormone levels (FSH, LH, and estradiol) before and after SARS-CoV-2 mRNA vaccination.

• 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.

• 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.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.28.1-28.25
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• 2020

The recent emergence of the novel coronavirus (CoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a global threat to human health and economy. As of June 26, 2020, over 9.4 million cases of infection, including 482,730 deaths, had been confirmed across 216 countries. To combat a devastating virus pandemic, numerous studies on vaccine development are urgently being accelerated. In this review article, we take a brief look at the characteristics of SARS-CoV-2 in comparison to SARS and Middle East respiratory syndrome (MERS)-CoVs and discuss recent approaches to coronavirus disease-2019 (COVID-19) vaccine development.

• Clinical and Experimental Pediatrics
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• v.64 no.4
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• pp.157-164
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• 2021

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, a small number of coronavirus disease 2019 (COVID-19) cases in neonates have been reported worldwide. Neonates currently account for only a minor proportion of the pediatric population affected by COVID-19. Thus, data on the epidemiological and clinical features of COVID-19 in neonates are limited. Approximately 3% of neonates born to mothers with COVID-19 reportedly tested positive for SARS-CoV-2. Current limited data on neonates with COVID-19 suggest that neonatal COVID-19 shows a relatively benign course despite a high requirement for mechanical ventilation. However, neonates with pre-existing medical conditions and preterm infants appear to be at a higher risk of developing severe COVID-19. The greatest perinatal concern of the COVID-19 pandemic is the possibility of vertical transmission, especially transplacental transmission of SARS-CoV-2. Although direct evidence of the vertical transmission of SARS-CoV-2 is lacking, its possibility during late pregnancy cannot be ruled out. This review summarizes available case studies on COVID-19 in neonates and introduces what is currently known about neonatal COVID-19 with focus on its vertical transmission.

• Journal of Veterinary Science
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• v.23 no.6
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• pp.80.1-80.6
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• 2022

A 10-year-old male neutered Labrador Retriever presented with a history of acute-onset tachypnoea, lethargy and anorexia. The dog was pyrexic, tachypnoeic and dyspnoeic on examination. A rapid antigen test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was performed on an oropharyngeal swab and yielded a positive result. SARS-CoV-2 infection was subsequently confirmed by reverse transcription polymerase chain reaction (RT-PCR) analysis. Both of the dog's owners had positive rapid antigen test and RT-PCR analysis results for SARS-CoV-2. Additional diagnostics included computed tomography. Resolution of the dog's clinical signs was achieved with symptomatic treatment.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1843-1853
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• 2020

COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread globally and caused serious social and economic problems. The WHO has declared this outbreak a pandemic. Currently, there are no approved vaccines or antiviral drugs that prevent SARS-CoV-2 infection. Drugs already approved for clinical use would be ideal candidates for rapid development as COVID-19 treatments. In this work, we screened 1,473 FDA-approved drugs to identify inhibitors of SARS-CoV-2 infection using cell-based assays. The antiviral activity of each compound was measured based on the immunofluorescent staining of infected cells using anti-dsRNA antibody. Twenty-nine drugs among those tested showed antiviral activity against SARS-CoV-2. We report this new list of inhibitors to quickly provide basic information for consideration in developing potential therapies.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.268-272
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• 2021

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.