Article
Virology
Mushtaq Hussain, Sanya Shabbir, Anusha Amanullah, Fozia Raza, Muhammad J. Imdad, Sahar Zahid
Summary: A newly emerged strain of SARS-CoV-2 B.1.1.7 lineage has caused a significant surge in infections in the UK. Changes in epitopes of spike and orf8 proteins were investigated, showing noticeable variations in spike proteins and antibody binding affinity. This study could be used to develop targeted immunotherapeutics.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Erik Volz, Swapnil Mishra, Meera Chand, Jeffrey C. Barrett, Robert Johnson, Lily Geidelberg, Wes R. Hinsley, Daniel J. Laydon, Gavin Dabrera, Aine O. Toole, Robert Amato, Manon Ragonnet-Cronin, Ian Harrison, Ben Jackson, Cristina Ariani, Olivia Boyd, Nicholas J. Loman, John T. McCrone, Sonia Goncalves, David Jorgensen, Richard Myers, Verity Hill, David K. Jackson, Katy Gaythorpe, Natalie Groves, John Sillitoe, Dominic P. Kwiatkowski, Seth Flaxman, Oliver Ratmann, Samir Bhatt, Susan Hopkins, Axel Gandy, Andrew Rambaut, Neil M. Ferguson
Summary: Genetic and testing data from England indicate that the SARS-CoV-2 variant B.1.1.7 has a transmission advantage over other lineages, showing a rapid expansion during autumn 2020. Analysis of S gene target failures (SGTF) in community-based diagnostic PCR testing suggests that B.1.1.7 is more transmissible than non-variant of concern lineages and has a significant transmission advantage, with a reproduction number 50% to 100% higher. Additionally, cases of B.1.1.7 appear to include a larger share of under 20-year-olds compared to non-variant cases.
Article
Multidisciplinary Sciences
Chiara Pastorio, Sabrina Noettger, Rayhane Nchioua, Fabian Zech, Konstantin M. J. Sparrer, Frank Kirchhoff
Summary: Additional mutations in the Spike protein of SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 help them outcompete the parental BA.2 subvariant. These mutations affect the infectivity, fusogenicity, and immune evasion of the virus, explaining the dominance and increased pathogenicity of these Omicron subvariants.
Article
Polymer Science
Quenisha Baldwin, Bobby Sumpter, Eleni Panagiotou
Summary: In this study, a mathematical method was used to characterize the local topology/geometry of the Spike protein backbone of SARS-CoV-2. The results showed that local conformational changes in certain domains were associated with global conformational changes in another domain. The analyzed variants of SARS-CoV-2 exhibited differences in local conformations, and mutations in or near high local topological free energy conformations were found to have a significant impact on protein function.
Article
Biochemistry & Molecular Biology
Nicole L. Washington, Karthik Gangavarapu, Mark Zeller, Alexandre Bolze, Elizabeth T. Cirulli, Kelly M. Schiabor Barrett, Brendan B. Larsen, Catelyn Anderson, Simon White, Tyler Cassens, Sharoni Jacobs, Geraint Levan, Jason Nguyen, Jimmy M. Ramirez, Charlotte Rivera-Garcia, Efren Sandoval, Xueqing Wang, David Wong, Emily Spencer, Refugio Robles-Sikisaka, Ezra Kurzban, Laura D. Hughes, Xianding Deng, Candace Wang, Venice Servellita, Holly Valentine, Peter De Hoff, Phoebe Seaver, Shashank Sathe, Kimberly Gietzen, Brad Sickler, Jay Antico, Kelly Hoon, Jingtao Liu, Aaron Harding, Omid Bakhtar, Tracy Basler, Brett Austin, Duncan MacCannell, Magnus Isaksson, Phillip G. Febbo, David Becker, Marc Laurent, Eric McDonald, Gene W. Yeo, Rob Knight, Louise C. Laurent, Eileen de Feo, Michael Worobey, Charles Y. Chiu, Marc A. Suchard, James T. Lu, William Lee, Kristian G. Andersen
Summary: The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has been spreading in the United States with multiple introductions as early as late November 2020. The variant shows a logistic growth rate with roughly weekly doubling and increased transmission, requiring immediate action to minimize COVID-19 morbidity and mortality.
Article
Chemistry, Medicinal
David Shorthouse, Benjamin A. Hall
Summary: Variants of SARS-CoV-2 with mutations in their spike protein are causing concerns for vaccine efficacy and pandemic control. Mutations in the spike protein are selecting for more thermodynamically stable amino acid changes, and computationally efficient analysis of mutational stability may aid in early screening of variants.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Public, Environmental & Occupational Health
Huaimin Yi, Jin Wang, Jiong Wang, Yuying Lu, Yali Zhang, Ruihao Peng, Jiahai Lu, Zeliang Chen
Summary: Since the outbreak of the COVID-19 pandemic, laboratories worldwide have been using whole genome sequencing to monitor the changes in the viral genes of SARS-CoV-2, leading to the discovery of multiple variants. Recent studies indicate that some new SARS-CoV-2 variants are more transmissible, impacting immune responses triggered by vaccines and natural infections, and reducing sensitivity to neutralizing antibodies.
FRONTIERS IN PUBLIC HEALTH
(2021)
Letter
Immunology
Patrick K. Mitchell, Mathias Martins, Tara Reilly, Leonardo C. Caserta, Renee R. Anderson, Brittany D. Cronk, Julia Murphy, Erin L. Goodrich, Diego G. Diel
Summary: Three Malayan tigers in a zoologic park in Virginia, USA were infected with the SARS-CoV-2 B.1.1.7 (Alpha) variant, showing respiratory signs consistent with infection. The findings indicate that tigers are susceptible to the SARS-CoV-2 B.1.1.7 variant.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Computer Science, Artificial Intelligence
Zeynep Banu Ozger, Pinar Cihan
Summary: This study proposed a new approach for successfully predicting B-cell epitopes for SARS-CoV-2. The results showed that the ensemble approach has the lowest error in B-cell epitope estimation, indicating its potential for effective prediction in this area.
APPLIED SOFT COMPUTING
(2022)
Letter
Immunology
Ingra Morales Claro, Flavia Cristina da Silva Sales, Mariana Severo Ramundo, Darlan S. Candido, Camila A. M. Silva, Jaqueline Goes de Jesus, Erika R. Manuli, Cristina Mendes de Oliveira, Luciano Scarpelli, Gustavo Campana, Oliver G. Pybus, Ester Cerdeira Sabino, Nuno Rodrigues Faria, Jose Eduardo Levi
Summary: In December 2020, the B.1.1.7 lineage of SARS-CoV-2 was detected in Sao Paulo, Brazil, with two distinct introductions identified through rapid genomic sequencing. There may be more infections with this lineage in Brazil than officially reported.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Microbiology
Michael H. Peters, Oscar Bastidas, Daniel S. Kokron, Christopher E. Henze
Summary: This study investigates the impact of mutations and deletions in the Spike protein of SARS-CoV-2 variants on vaccines and therapeutics. Through biophysics and phylogenetic analysis, key residue mutations and stabilizing glue points associated with variants are identified. Computational studies on trimeric Spike protein variants reveal structural and energetic changes, highlighting the importance of certain mutations on protein structure and binding. Understanding similarities and differences between variants is crucial for determining functional features and possible transmission and infection differences among lineages.
MICROBIOLOGY SPECTRUM
(2021)
Article
Biochemistry & Molecular Biology
Sk Sarif Hassan, Kenneth Lundstrom, Debmalya Barh, Raner Jose Santana Silva, Bruno Silva Andrade, Vasco Azevedo, Pabitra Pal Choudhury, Giorgio Palu, Bruce D. Uhal, Ramesh Kandimalla, Murat Seyran, Amos Lal, Samendra P. Sherchan, Gajendra Kumar Azad, Alaa A. A. Aljabali, Adam M. Brufsky, Angel Serrano-Aroca, Parise Adadi, Tarek Mohamed Abd El-Aziz, Elrashdy M. Redwan, Kazuo Takayama, Nima Rezaei, Murtaza Tambuwala, Vladimir N. Uversky
Summary: The spike protein of SARS-CoV-2 plays a critical role in infectivity and antigenicity. Unique variants of the spike protein have been identified on different continents, with North America exhibiting significant differences compared to others. International travel may facilitate the spread of new variants, suggesting the importance of travel restrictions and mass vaccination in controlling the pandemic. Reviewing and potentially re-engineering vaccines to address emerging spike protein variants is also recommended.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Immunology
Ranjith Kumavath, Debmalya Barh, Bruno Silva Andrade, Madangchanok Imchen, Flavia Figueira Aburjaile, Athira Ch, Diego Lucas Neres Rodrigues, Sandeep Tiwari, Khalid J. Alzahrani, Aristoteles Goes-Neto, Marianna E. Weener, Preetam Ghosh, Vasco Azevedo
Summary: This review covers the critical role of the Spike protein of the SARS-CoV-2 virus in infection and transmission, as well as recent advances in detection methods and vaccine efficacy. The review also discusses interactions with the host, implications in COVID-19 pathogenesis, and emerging Spike mutants.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Infectious Diseases
Ahmed M. Almehdi, Ghalia Khoder, Aminah S. Alchakee, Azizeh T. Alsayyid, Nadin H. Sarg, Sameh S. M. Soliman
Summary: The study highlights the distinct structural features of the SARS-CoV-2 S protein, its crucial role in pathogenesis, and its potential in developing therapies and vaccines. Understanding the significance of the S protein in viral infection and the development of therapeutic compounds and vaccines may lead to a significant reduction in the global health burden of the COVID-19 pandemic, although the efficacy and safety of these treatments remain debated.
Article
Microbiology
Ivette A. Nunez, Christopher Z. Lien, Prabhuanand Selvaraj, Charles B. Stauft, Shufeng Liu, Matthew F. Starost, Tony T. Wang
Summary: The study reveals that immunity acquired through a prior infection with the first-wave variant provides nearly complete protection against the B.1.1.7 variant in Syrian hamsters upon reexposure. Although the B.1.1.7 variant replicates to a higher level in the nose than the ancestral B.1 variant, it does not induce more severe lung pathology in the hamsters.
Article
Biochemistry & Molecular Biology
Ting Chen, Hung-Wei Yeh, Po-Pang Chen, Wei-Ting Huang, Chu-Ya Wu, Tzu-Chen Liao, Shiou-Lan Lin, Yi-Yun Chen, Kai-Ti Lin, Shang-Te Danny Hsu, Hui-Chun Cheng
Summary: The study revealed the molecular basis of OLA1-BARD1 interaction, showing that the BARD1 BRCT domain serves as an ATPase activating protein to control OLA1 activity allosterically.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Cell Biology
Tzu-Jing Yang, Tian-Neng Li, Rih-Sheng Huang, Max Yu-Chen Pan, Shu-Yu Lin, Steven Lin, Kuen-Phon Wu, Lily Hui-Ching Wang, Shang-Te Danny Hsu
Summary: The subcellular localization of BAP1 is crucial for its tumor suppressor activity. This study reveals that transportin-1 (TNPO1) plays a key role in the nuclear import of BAP1 by binding to its unique nuclear localization signal (PY-NLS) motif. TNPO1 also dissociates the dimeric structure of BAP1 and prevents its monoubiquitination to counteract the cytosolic retention by UBE2O.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarita Puri, Szu-Ni Chen, Yi-Hsiang Chiu, Piotr Draczkowski, Kuang-Ting Ko, Tzu-Jing Yang, Yong-Sheng Wang, Susumu Uchiyama, Shang-Te Danny Hsu
Summary: This study investigates the effects of non-catalytic mutations within BAP1-UCH on the structure and function of the protein. The findings reveal that these mutations can lead to protein instability and increased aggregation propensity, providing insights into the molecular basis of their involvement in oncogenesis.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Limnology
Chih-Chang Chen, Irene B. Rodriguez, Yuh-ling Lee Chen, Jonathan P. Zehr, Yun-Ru Chen, Shang-Te Danny Hsu, Shun-Chung Yang, Tung-Yuan Ho
Summary: Under high solar radiation conditions, nickel superoxide dismutase (NiSOD) protects the nitrogen fixation process of Trichodesmium from oxidative stress, allowing it to provide a significant amount of bioavailable nitrogen in challenging ocean environments.
LIMNOLOGY AND OCEANOGRAPHY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Hui-Ju Huang, Sen-Lin Tang, Yuan-Chih Chang, Hao-Ching Wang, Tze Hann Ng, Rees F. Garmann, Yu-Wen Chen, Jiun-Yan Huang, Ramya Kumar, Sheng-Hsiung Chang, Shang-Rung Wu, Chih-Yu Chao, Kyoko Matoba, Iwasaki Kenji, William M. Gelbart, Tzu-Ping Ko, Hwei-Jiung (Andrew) Wang, Chu-Fang Lo, Li-Li Chen, Han-Ching Wang
Summary: Transmission electron microscopy (TEM) and cryogenic electron microscopy (Cryo-EM) techniques were used to study the morphology and pathogenesis of White spot syndrome virus (WSSV). The mature WSSV virions were found to have an oval shape without tail-like extensions. Two distinct ends, a portal cap, and a closed base, were observed in WSSV nucleocapsids. A C14 symmetric structure of the WSSV nucleocapsid was proposed based on Cryo-EM map. Immunoelectron microscopy (IEM) revealed a ring-like architecture formed by VP664 proteins, the main components of the 14 assembly units, in WSSV. Furthermore, a unique helical dissociation process of WSSV nucleocapsids was observed. Based on these findings, a novel morphogenetic pathway of WSSV was proposed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Meng-Ru Ho, Yi-Ming Wu, Yen-Chen Lu, Tzu-Ping Ko, Kuen-Phon Wu
Summary: In this study, a cryo-electron microscopy (cryo-EM) structure of a 723-amino acid protein called malate synthase G (MSG) from Escherichia coli was determined at a resolution of 2.9 A. The cryo-EM structure of this 82-kDa protein was found to be similar to structures resolved by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, with no distinguishable differences. The study also revealed consistent conformational flexibilities among different experimental approaches, particularly in the alpha/beta domain. Additionally, differences in sidechain rotations of certain residues involved in hosting the cofactor acetyl-CoA and substrate were observed between the cryo-EM apo-form and complex crystal structures. These findings demonstrate that cryo-EM can be used to determine the structures and conformational heterogeneity of sub-100 kDa biomolecules with a quality comparable to X-ray crystallography and NMR spectroscopy.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Chu-Wei Kuo, Ning-En Chang, Pei-Yu Yu, Tzu-Jing Yang, Shang-Te Danny Hsu, Kay-Hooi Khoo
Summary: To fully identify all N-glycosylation sites on the SARS-CoV2 spike protein, multiple proteases are needed in addition to trypsin. The commonly used Byonic software for peptide identification often introduces errors due to similar mass differences. By manually interpreting MS2 spectra, this study identifies common errors, especially those caused by chymotrypsin. By using a stringent acceptance threshold and considering results from the pGlyco3 search engine, erroneous assignment can be controlled within 15% in Byonic. A representative N-glycosylation pattern can be constructed by quantifying the overlapping subset of confidently identified N-glycopeptides. Applying two complimentary glycoproteomic software tools, this study confirms significant differences in glycosylation at certain sites between the unstable Omicron spike protein and the stable trimeric form of the parental D614G variant.
Article
Multidisciplinary Sciences
Ruei-Min Lu, Kang-Hao Liang, Hsiao-Ling Chiang, Fu-Fei Hsu, Hsiu-Ting Lin, Wan-Yu Chen, Feng-Yi Ke, Monika Kumari, Yu-Chi Chou, Mi-Hua Tao, Yi-Ling Lin, Han-Chung Wu
Summary: The COVID-19 pandemic continues to pose a threat to human health globally with the emergence of new SARS-CoV-2 variants. This study developed a set of monoclonal antibodies targeting the Omicron variants using the mRNA-lipid nanoparticle immunization method. These antibodies demonstrated strong binding and neutralizing activities against all SARS-CoV-2 variants, including Omicron, suggesting their potential as universal neutralizing antibodies against SARS-CoV-2.
Article
Chemistry, Multidisciplinary
Yu-Chun Chien, Yong-Sheng Wang, Deepa Sridharan, Chu-Wei Kuo, Chih-Ta Chien, Takayuki Uchihashi, Koichi Kato, Takashi Angata, Tzu-Ching Meng, Shang-Te Danny Hsu, Kay-Hooi Khoo
Summary: The intracellular phosphatase domain of PTPRA plays a crucial role in regulating cell adhesion through c-Src kinase activation. The site-specific glycosylation pattern of the heavily glycosylated ectodomain of PTPRA has been determined, revealing the presence of O-glycan at the N-glycosylation sites. The structural features of the ectodomain, combined with the glycosylation information, support the dynamic structural model of the densely glycosylated PTPRA ectodomain.
Article
Biochemistry & Molecular Biology
Sarita Puri, Cheng-Yu Liu, I-Chen Hu, Chih-Hsuan Lai, Shang-Te Danny Hsu, Ping-Chiang Lyu
Summary: In this study, the conformational and stability changes of the CP74 protein were investigated by substituting tryptophan residues with phenylalanine. The results showed minimal perturbations to the native structures in the tryptophan variants and the conservation of the domain-swapped ternary structure. However, asymmetry was observed in the a-helix 5 of the W72F variant. Thermal and chemical stability analyses indicated the important role of W100 in the folding of CP74, followed by W19 and W72. NMR spectroscopy and mass spectrometry revealed the accumulation of a native-like intermediate state where the hinge region contributed to maintaining the domain-swapped ternary structure of CP74.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Cheng-Pu Sun, Chi-Wen Chiu, Ping-Yi Wu, Szu- Tsung, I-Jung Lee, Chih-Wei Hu, Min-Feng Hsu, Tzu-Jiun Kuo, Yu-Hua Lan, Li-Yao Chen, Hui-Yee Ng, Meng-Jhe Chung, Hsin-Ni Liao, Sheng-Che Tseng, Chia-Hui Lo, Yung-Jiun Chen, Chun-Che Liao, Chih-Shin Chang, Jian-Jong Liang, Piotr Draczkowski, Sarita Puri, Yuan-Chih Chang, Jing-Siou Huang, Cheng-Cheung Chen, Jyh-Hwa Kau, Yen-Hui Chen, Wen-Chun Liu, Han-Chun Wu, Shang-Te Danny, I-Hsuan Wang, Mi-Hua Tao
Summary: The study isolated and humanized a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, which effectively blocked the binding of viral receptor-binding domain (RBD) to hACE2. In vitro and in vivo experiments demonstrated that the ch2H2 antibody exhibited potent inhibitory activity against multiple SARS-CoV-2 variants, including the Omicron variant. The adeno-associated virus (AAV)-mediated delivery of the antibody also showed promising results in reducing viral load and mitigating pulmonary pathological changes.
Article
Biochemical Research Methods
Hsi-Wen Kao, Wei-Lin Lu, Meng-Ru Ho, Yu-Fong Lin, Yun-Jung Hsieh, Tzu-Ping Ko, Shang-Te Danny Hsu, Kuen-Phon Wu
Summary: We used ProteinMPNN, a deep learning tool, to redesign ubiquitin (Ub) as a specific and functionally stimulating/enhancing binder of the Rsp5 E3 ligase. We generated 20 extensively mutated Ub variants (UbVs) named R1 to R20, which displayed well-folded structures and high thermal stabilities. These UbVs can form stable complexes with Rsp5, as predicted by AlphaFold2. Three of the UbVs showed low micromolar affinity to Rsp5, with R4 and R12 effectively enhancing Rsp5 activity six folds. AlphaFold2 predicts that R4 and R12 bind to Rsp5's exosite in the same manner as the Rsp5-Ub template, thereby allosterically activating Rsp5-Ub thioester formation. Thus, we present a virtual solution for rapidly and cost-effectively designing functional modulators of Ub-related enzymes.
ACS SYNTHETIC BIOLOGY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Shang-Te Danny Hsu, Tzu-Jing Yang, Pei-Yu Yu, Yu-Xi Tsai, Ning-En Chang, Kay-Hooi Khoo, Cyril Hanus, Mateusz Sikora
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shang-Te Danny Hsu
Summary: The topologically knotted proteins have entangled structural elements that play a crucial role in their folding, stability, and biological functions.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)