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Article ; Online: Ancestral, Delta, and Omicron (BA.1) SARS-CoV-2 strains are dependent on serine proteases for entry throughout the human respiratory tract.

Gartner, Matthew J / Lee, Leo Yi Yang / Mordant, Francesca L / Suryadinata, Randy / Chen, Joseph / Robinson, Philip / Polo, Jose M / Subbarao, Kanta

Med (New York, N.Y.)

2023 Volume 4, Issue 12, Page(s) 944–955.e7

Abstract: Background: The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and became the globally dominant variant by January 2022. Authentic virus and pseudovirus systems have shown Omicron spike has an increased dependence on the endosomal pathway for ... ...

Abstract	Background: The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and became the globally dominant variant by January 2022. Authentic virus and pseudovirus systems have shown Omicron spike has an increased dependence on the endosomal pathway for entry. Methods: We investigated the entry mechanisms of Omicron, Delta, and ancestral viruses in cell models that represent different parts of the human respiratory tract, including nasal epithelial cells (hNECs), large-airway epithelial cells (LAECs), small-airway epithelial cells, and embryonic stem cell-derived type II alveolar cells. Findings: Omicron had an early replication advantage in LAECs, while Delta grew to higher titers in all cells. Omicron maintained dependence on serine proteases for entry in all culture systems. While serine protease inhibition with camostat was less robust for Omicron in hNECs, endosomal entry was not enhanced. Conclusions: Our findings demonstrate that entry of Omicron BA.1 SARS-CoV-2 is dependent on serine proteases for entry throughout the respiratory tract. Funding: This work was supported by The Medical Research Future Fund (MRF9200007; K.S., J.M.P.) and the DHHS Victorian State Government grant (Victorian State Government; DJPR/COVID-19; K.S, J.M.P.). K.S. is supported by a National Health and Medical Research Council of Australia Investigator grant (APP1177174).
MeSH term(s)	Humans ; Serine Proteases/genetics ; SARS-CoV-2/genetics ; COVID-19/epidemiology ; Serine Endopeptidases/genetics ; Respiratory System
Chemical Substances	Serine Proteases (EC 3.4.-) ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2023.08.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A Review of DNA Vaccines Against Influenza.

Lee, Leo Yi Yang / Izzard, Leonard / Hurt, Aeron C

Frontiers in immunology

2018 Volume 9, Page(s) 1568

Abstract: The challenges of effective vaccination against influenza are gaining more mainstream attention, as recent influenza seasons have reported low efficacy in annual vaccination programs worldwide. Combined with the potential emergence of novel influenza ... ...

Abstract	The challenges of effective vaccination against influenza are gaining more mainstream attention, as recent influenza seasons have reported low efficacy in annual vaccination programs worldwide. Combined with the potential emergence of novel influenza viruses resulting in a pandemic, the need for effective alternatives to egg-produced conventional vaccines has been made increasingly clear. DNA vaccines against influenza have been in development since the 1990s, but the initial excitement over success in murine model trials has been tempered by comparatively poor performance in larger animal models. In the intervening years, much progress has been made to refine the DNA vaccine platform-the rational design of antigens and expression vectors, the development of novel vaccine adjuvants, and the employment of innovative gene delivery methods. This review discusses how these advances have been applied in recent efforts to develop an effective influenza DNA vaccine.
Language	English
Publishing date	2018
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.01568
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Author Correction: Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses.

McMillan, Christopher L D / Cheung, Stacey T M / Modhiran, Naphak / Barnes, James / Amarilla, Alberto A / Bielefeldt-Ohmann, Helle / Lee, Leo Yi Yang / Guilfoyle, Kate / van Amerongen, Geert / Stittelaar, Koert / Jakob, Virginie / Lebas, Celia / Reading, Patrick / Short, Kirsty R / Young, Paul R / Watterson, Daniel / Chappell, Keith J

NPJ vaccines

2022 Volume 7, Issue 1, Page(s) 3

Language	English
Publishing date	2022-01-05
Publishing country	England
Document type	Published Erratum
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-021-00428-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells.

Lee, Leo Yi Yang / Suryadinata, Randy / McCafferty, Conor / Ignjatovic, Vera / Purcell, Damian F J / Robinson, Phil / Morton, Craig J / Parker, Michael W / Anderson, Gary P / Monagle, Paul / Subbarao, Kanta / Neil, Jessica A

Viruses

2022 Volume 14, Issue 12

Abstract: SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants ... ...

Abstract	SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies.
MeSH term(s)	Humans ; COVID-19 ; Epithelial Cells/virology ; Heparin/pharmacology ; Pandemics ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Replication/drug effects
Chemical Substances	Heparin (9005-49-6) ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14122620
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Article ; Online: Portosystemic Shunt in Pediatric Living Donor Liver Transplant.

Lim, Wei-Xiong / Lin, An-Ni / Cheng, Yu-Fan / Lee, Sieh-Yang / Hsu, Hsien-Wen / Chen, Chao-Long / Chang, Wan-Ching / Yu, Chun-Yen / Tsang, Leo Leung-Chit / Chuang, Yi-Hsuan / Ou, Hsin-You

Transplantation proceedings

2022 Volume 54, Issue 2, Page(s) 403–405

Abstract: Background: To evaluate the significance of portosystemic shunts and associated long-term outcomes in living donor liver transplant (LDLT) among pediatric patients.: Methods: Retrospective review of 121 pediatric patients who underwent LDLT between ... ...

Abstract	Background: To evaluate the significance of portosystemic shunts and associated long-term outcomes in living donor liver transplant (LDLT) among pediatric patients. Methods: Retrospective review of 121 pediatric patients who underwent LDLT between May 1994 and December 2015 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and postoperative computed tomography images of the liver were reviewed, and portal vein complications were assessed. Results: Ninety-seven pediatric patients were included in the study, and 70 had portosystemic shunts before transplant. Thirty-three patients have portal systemic shunt (PSS) 6 months after transplant (mean [SD] shunt size, 4.59 [1.98] mm). Thirty-seven patients' portosystemic shunts closed spontaneously (mean [SD] shunt size, 3.14 [1.06] mm). Smaller PSSs tend to close spontaneously with a cutoff point of 3.35 mm by receiver operating characteristic curve (P = .01). Patients with PSS have more portal vein complications than those without PSS (44.3% vs 11.1%, P = .02). Among PSS recipients, patients with portal vein complications tend to have larger PSS size (mean [SD], 4.14 [1.96] mm vs 3.59 [1.48] mm), although the difference is not statistically significant (P = .19). Conclusions: In pediatric patients, preoperative portosystemic shunts are significantly correlated with portal venous complications, some of which require minimal interventions after LDLT with good outcomes. Shunts larger than 3.35 mm tend to persist after transplant with increased portal venous complications.
MeSH term(s)	Child ; Humans ; Liver Transplantation ; Living Donors ; Portal Vein/diagnostic imaging ; Portal Vein/surgery ; Portasystemic Shunt, Surgical/adverse effects ; Portasystemic Shunt, Surgical/methods ; Portasystemic Shunt, Transjugular Intrahepatic ; Retrospective Studies
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	82046-5
ISSN	1873-2623 ; 0041-1345
ISSN (online)	1873-2623
ISSN	0041-1345
DOI	10.1016/j.transproceed.2021.09.072
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment.

Rudraraju, Rajeev / Gartner, Matthew J / Neil, Jessica A / Stout, Elizabeth S / Chen, Joseph / Needham, Elise J / See, Michael / Mackenzie-Kludas, Charley / Yang Lee, Leo Yi / Wang, Mingyang / Pointer, Hayley / Karavendzas, Kathy / Abu-Bonsrah, Dad / Drew, Damien / Yang Sun, Yu Bo / Tan, Jia Ping / Sun, Guizhi / Salavaty, Adrian / Charitakis, Natalie /

Nim, Hieu T / Currie, Peter D / Tham, Wai-Hong / Porrello, Enzo / Polo, Jose M / Humphrey, Sean J / Ramialison, Mirana / Elliott, David A / Subbarao, Kanta

Stem cell reports

2023 Volume 18, Issue 6, Page(s) 1308–1324

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.
MeSH term(s)	Humans ; SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Stem Cells ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Lung
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Antiviral Agents
Language	English
Publishing date	2023-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2023.05.007
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Characterization of Low-Loss Dielectric Materials for High-Speed and High-Frequency Applications.

Lee, Tzu-Nien / Lau, John-H / Ko, Cheng-Ta / Xia, Tim / Lin, Eagle / Yang, Kai-Ming / Lin, Puru-Bruce / Peng, Chia-Yu / Chang, Leo / Chen, Jia-Shiang / Fang, Yi-Hsiu / Liao, Li-Yueh / Charn, Edward / Wang, Jason / Tseng, Tzyy-Jang

Materials (Basel, Switzerland)

2022 Volume 15, Issue 7

Abstract: In this study, the Df (dissipation factor or loss tangent) and Dk (dielectric constant or permittivity) of the low-loss dielectric material from three different vendors are measured by the Fabry-Perot open resonator (FPOR) technique. Emphasis is placed ... ...

Abstract	In this study, the Df (dissipation factor or loss tangent) and Dk (dielectric constant or permittivity) of the low-loss dielectric material from three different vendors are measured by the Fabry-Perot open resonator (FPOR) technique. Emphasis is placed on the sample preparation, data collection, and the comparison with the data sheet values provided from vendors. A coplanar waveguide with ground (CPWG) test vehicle with one of these raw dielectric materials (vendor 1) is designed (through Polar and simulation) and fabricated. The impedance of the test vehicle is measured by TDR (time-domain reflectometer), and the effective Dk of the test vehicle is calculated by the real cross-section of the metal line width, spacing, and thickness of the test vehicle and a closed-form equation. In parallel, the insertion loss and return loss are measured with the VNA (vector network analyzer) of the test vehicle. Finally, the measurement and simulation results are correlated. Some recommendations on the low-loss dielectric materials of the Dk and Df are also provided.
Language	English
Publishing date	2022-03-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma15072396
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Robustness of the Ferret Model for Influenza Risk Assessment Studies: a Cross-Laboratory Exercise.

mBio

2022 Volume 13, Issue 4, Page(s) e0117422

Abstract: Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information ... ...

Abstract	Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses. However, small sample sizes and a lack of standardized protocols can introduce interlaboratory variability, complicating interpretation of transmission experimental data. To assess the range of variation in ferret transmission experiments, a global exercise was conducted by 11 laboratories using two common stock H1N1 influenza viruses with different transmission characteristics in ferrets. Parameters known to affect transmission were standardized, including the inoculation route, dose, and volume, as well as a strict 1:1 donor/contact ratio for respiratory droplet transmission. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored and analyzed. The overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. Among environmental parameters that varied across laboratories, donor-to-contact airflow directionality was associated with increased transmissibility. To attain high confidence in identifying viruses with moderate to high transmissibility or low transmissibility under a smaller number of participating laboratories, our analyses support the notion that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment.
MeSH term(s)	Animals ; Ferrets ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; Laboratories ; Lung ; Orthomyxoviridae Infections ; Risk Assessment
Language	English
Publishing date	2022-07-11
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.01174-22
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Article: A novel and highly divergent Canine Distemper Virus lineage causing distemper in ferrets in Australia

George, Ankita M. / Wille, Michelle / Wang, Jianning / Anderson, Keith / Cohen, Shari / Moselen, Jean / Yang Lee, Leo Yi / Suen, Willy W. / Bingham, John / Dalziel, Antonia E. / Whitney, Paul / Stannard, Harry / Hurt, Aeron C. / Williams, David T. / Deng, Yi-Mo / Barr, Ian G.

Virology. 2022 Sept. 04,

2022

Abstract: Canine distemper virus (CDV) causes a highly contagious systemic infection in an array of animal species. In this study we report an outbreak of distemper in ferrets in two research facilities in Australia, caused by a novel lineage of CDV. While the CDV ...

Abstract	Canine distemper virus (CDV) causes a highly contagious systemic infection in an array of animal species. In this study we report an outbreak of distemper in ferrets in two research facilities in Australia, caused by a novel lineage of CDV. While the CDV strain caused mainly mild symptoms in ferrets, histopathology results presented a typical profile of distemper pathology, with multi-system virus replication. Through the development of a discriminatory PCR, paired with full genome sequencing, we revealed that the outbreak was caused by a novel lineage of CDV. The novel CDV lineage was highly divergent, with less than 93% similarity across the H gene to other described lineages, including the vaccine strain, and diverged approximately 140–400 years ago. Enhanced surveillance to determine the prevalence of CDV in ferrets, dogs and other at-risk species is critical to better understand the presence and diversity of CDV in Australia currently.
Keywords	Canine morbillivirus ; animals ; distemper ; genes ; histopathology ; monitoring ; vaccines ; virus replication ; Australia
Language	English
Dates of publication	2022-0904
Publishing place	Elsevier Inc.
Document type	Article
Note	Pre-press version
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2022.09.001
Database	NAL-Catalogue (AGRICOLA)

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Article: Parallel use of pluripotent human stem cell lung and heart models provide new insights for treatment of SARS-CoV-2.

Rudraraju, Rajeev / Gartner, Matthew J / Neil, Jessica A / Stout, Elizabeth S / Chen, Joseph / Needham, Elise J / See, Michael / Mackenzie-Kludas, Charley / Yang Lee, Leo Yi / Wang, Mingyang / Pointer, Hayley / Karavendzas, Kathy / Abu-Bonsrah, Dad / Drew, Damien / Sun, Yu Bo Yang / Tan, Jia Ping / Sun, Guizhi / Salavaty, Abbas / Charitakis, Natalie /

Nim, Hieu T / Currie, Peter D / Tham, Wai-Hong / Porrello, Enzo / Polo, Jose / Humphrey, Sean J / Ramialison, Mirana / Elliott, David A / Subbarao, Kanta

bioRxiv : the preprint server for biology

2022

Abstract: SARS-CoV-2 primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe COVID-19. To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type ... ...

Abstract	SARS-CoV-2 primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe COVID-19. To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR- Cas9 mediated knock-out of ACE2, we demonstrated that angiotensin converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but further processing in lung cells required TMPRSS2 while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems. One-sentence summary: Rational treatment strategies for SARS-CoV-2 derived from human PSC models.
Language	English
Publishing date	2022-09-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.09.20.508614
Database	MEDical Literature Analysis and Retrieval System OnLINE

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