Article
Medicine, Research & Experimental
Kuo-Yen Huang, Ming-Shiu Lin, Ting-Chun Kuo, Ci-Ling Chen, Chung-Chih Lin, Yu-Chi Chou, Tai-Ling Chao, Yu-Hao Pang, Han-Chieh Kao, Rih-Sheng Huang, Steven Lin, Sui-Yuan Chang, Pan-Chyr Yang
Summary: The humanized decoy antibody, ACE2-Fc fusion protein, effectively blocks SARS-CoV-2 virus entry and replication by targeting the interaction between the viral spike protein and its cellular receptor. It shows efficient inhibition against different virus strains, including variants with increased infectivity.
EMBO MOLECULAR MEDICINE
(2021)
Article
Immunology
Janeri Froberg, Vera J. C. H. Koomen, Christa E. van der Gaast-de Jongh, Ria Philipsen, Corine H. Geurtsvankessel, Rory D. de Vries, Marije C. Baas, Renate G. van der Molen, Marien de Jonge, Luuk B. Hilbrands, Martijn A. Huynen, Dimitri A. Diavatopoulos, RECOVAC Consortium
Summary: This study found that mucosal IgA concentrations were significantly higher postinfection compared to postvaccination, while vaccination induced higher IgG concentrations. However, the ACE2-inhibiting activity did not differ between the two cohorts. Binding inhibition post-infection was driven by both IgA and IgG, while post-vaccination binding inhibition was mainly driven by IgG.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Microbiology
Aitor Casas-Sanchez, Alessandra Romero-Ramirez, Eleanor Hargreaves, Cameron C. Ellis, Brian Grajeda, Igor L. Estevao, Edward Patterson, Grant L. Hughes, Igor C. Almeida, Tobias Zech, Alvaro Acosta-Serrano
Summary: The study demonstrates that interfering with the N-glycosylation of spike proteins can significantly reduce the spread of SARS-CoV-2 infection, including various variants. As new SARS-CoV-2 variants with different levels of resistance against current vaccines are likely to appear, targeting the virus glycosylation using approved human drugs could be a complementary strategy to reduce the global spread of COVID-19.
Article
Multidisciplinary Sciences
James A. Torchia, Alexander H. Tavares, Laura S. Carstensen, Da -Yuan Chen, Jessie Huang, Tianshu Xiao, Sonia Mukherjee, Patrick M. Reeves, Hua Tu, Ann E. Sluder, Bing Chen, Darrell N. Kotton, Richard A. Bowen, Mohsan Saeed, Mark C. Poznansky, Gordon J. Freeman
Summary: As the SARS-CoV-2 virus evolves to evade natural antibodies, it also becomes less sensitive to therapeutic antibody drugs. However, an ACE2 decoy provides a neutralizing effect against antibody-resistant variants, including Omicron, without losing its potency. The inclusion of the ACE2 collectrin-like domain in the decoy not only improves its affinity for the viral S protein, but also unexpectedly prolongs its half-life in the blood and is necessary for reducing disease severity and viral replication in Syrian hamsters. The decoys' activity is attributed to their ability to trigger irreversible structural changes in the viral S protein.
Article
Virology
Chen Huang, Yu Jiang, Jie Yan
Summary: This study identified that some animals lack key receptors for binding to SARS-CoV-2, potentially reducing their susceptibility to the virus. Additionally, it was found that Ace2 in animals may have lower affinity for SARS-CoV-2 binding compared to human ACE2. The research sheds light on the human-to-animal transmission of SARS-CoV-2.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Nanoscience & Nanotechnology
Ruomeng Qiu, Feng Chen, Zaida Alvarez, Tristan D. Clemons, Suvendu Biswas, Mark R. Karver, Nozomu Takata, Hiroaki Sai, Han Peng, Steven Weigand, Liam C. Palmer, Samuel I. Stupp
Summary: This study reports a method that blocks the interaction between SARS-CoV-2 and ACE2 by displaying ACE2 sequence on the surface of supramolecular nanofibers, offering promising therapeutic opportunities to prevent viral infection. The results demonstrate that this method maintains the secondary structure of ACE2 and blocks the entry of pseudovirus and its variants into human cells, while enhancing the chemical stability of bioactive structures in the supramolecular environment. These findings reveal the unique advantages of supramolecular peptide therapies for preventing viral infections and other targets.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Pharmacology & Pharmacy
Siew Pheng Lim
Summary: Despite the availability of vaccines and therapeutics, continuous genetic alterations in the SARS-CoV-2 virus pose a persistent threat, especially to immunocompromised and elderly individuals. The virus enters host cells via the interaction of its spike protein (S protein) with different receptors on the cell surface, such as angiotensin-converting enzyme 2 (ACE2). This review discusses therapeutic approaches to block the interaction between SARS-CoV-2 and host cell receptors, as well as the identification of auxiliary entry receptors.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yu Hu, Kefang Liu, Pu Han, Zepeng Xu, Anqi Zheng, Xiaoqian Pan, Yunfei Jia, Chao Su, Lingfeng Tang, Lili Wu, Bin Bai, Xin Zhao, Di Tian, Zhihai Chen, Jianxun Qi, Qihui Wang, George F. Gao
Summary: Bat-origin RshSTT182 and RshSTT200 coronaviruses from Rhinolophus shameli in Southeast Asia (Cambodia) have 92.6% whole-genome identity with SARS-CoV-2 and share identical receptor-binding domains (RBDs). The study determined the structure of the RshSTT182/200 RBD in complex with human angiotensin-converting enzyme 2 (hACE2) and identified key residues influencing receptor binding. RshSTT182 pseudovirus could enter cells by utilizing human, fox, and Rhinolophus affinis ACE2 receptors, and SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus.
Article
Infectious Diseases
Fabian Z. X. Lean, Alejandro Nunez, Simon Spiro, Simon L. Priestnall, Sandra Vreman, Dalan Bailey, Joe James, Ethan Wrigglesworth, Alejandro Suarez-Bonnet, Carina Conceicao, Nazia Thakur, Alexander M. P. Byrne, Stuart Ackroyd, Richard J. Delahay, Wim H. M. van der Poel, Ian H. Brown, Anthony R. Fooks, Sharon M. Brookes
Summary: ACE2 serves as the receptor for coronaviruses and shows varied distribution in different animal tissues, affecting host susceptibility. The presence of ACE2 in the respiratory tract varies among species, providing insights into the receptor-mediated viral infection.
TRANSBOUNDARY AND EMERGING DISEASES
(2022)
Review
Virology
Shuvomoy Banerjee, Xinyu Wang, Shujuan Du, Caixia Zhu, Yuping Jia, Yuyan Wang, Qiliang Cai
Summary: This review summarizes the characteristics and pathogenic mechanisms of SARS-CoV-2 infection, focusing on the interaction between the spike glycoprotein and host factors. The authors highlight the importance of the spike protein in viral entry and pathogenesis, and discuss the progress of potential therapeutic targets and prophylactic and therapeutic agents for SARS-CoV-2 infection.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Infectious Diseases
Shan Gao, Junwen Luan, Haoran Cui, Leiliang Zhang
Summary: The study shows that different ACE2 isoforms in mammals can affect their susceptibility to SARS-CoV-2, making some mammals more susceptible to infection while others are less susceptible.
TRANSBOUNDARY AND EMERGING DISEASES
(2021)
Article
Cell Biology
Thankamani Karthika, Jeswin Joseph, V. R. Akshay Das, Niranjana Nair, Packirisamy Charulekha, Melvin Daniel Roji, V. Stalin Raj
Summary: The cytoplasmic tail of ACE2 is not essential for the entry of SARS-CoV-1 and -2, suggesting that their entry may be mediated via known or unknown host factors. Inhibition of pseudotyped SARS-CoVs entry into cells was observed when treated with a dynamin inhibitor and an endosomal acidification inhibitor. Antibodies against SARS-CoV and soluble ACE2 were unable to enter cells expressing wtACE2 and increment cytACE2.
Article
Multidisciplinary Sciences
Yinghui Liu, Gaowei Hu, Yuyan Wang, Wenlin Ren, Xiaomin Zhao, Fansen Ji, Yunkai Zhu, Fei Feng, Mingli Gong, Xiaohui Ju, Yuanfei Zhu, Xia Cai, Jun Lan, Jianying Guo, Min Xie, Lin Dong, Zihui Zhu, Jie Na, Jianping Wu, Xun Lan, Youhua Xie, Xinquan Wang, Zhenghong Yuan, Rong Zhang, Qiang Ding
Summary: Epidemiological studies have shown that bats are the natural reservoir of SARS-CoV-2, but the host range and intermediate hosts for transmission are unknown. This study characterized the ability of ACE2 from various species to support viral entry, suggesting a potentially broad host tropism of SARS-CoV-2. Analysis of ACE2 orthologs revealed that New World monkey ACE2 could not support viral entry, with genetic determinants restricting this interaction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Sara Ricardo, Pedro Canao, Diana Martins, Ana C. Magalhaes, Marina Pereira, Ulysses Ribeiro-Junior, Evandro Sobroza de Mello, Venancio A. Alves, Regina Pinto, Dina Leitao, Georgina Alves, Rute Oliveira, Joana Wilton, Susete Costelha, Diana Meireles, Didier Cabanes, Leonor David, Fernando Schmitt
Summary: This study evaluated the expression of ACE2 and furin in cancer cells and found that colon and gastric carcinoma cells have high expression levels of ACE2 and furin, while thyroid carcinoma cells do not express ACE2. Although some cases tested positive for SARS-CoV-2 by tissue section PCR, immunohistochemistry and in situ hybridization did not show viral presence in the cancer cells. This study raises the possibility of ACE2-mediated viral tropism in cancer tissues to be clarified in future studies.
Article
Cell Biology
Rocio Diaz Escarcega, Pedram Honarpisheh, Gabriela Delevati Colpo, Hilda W. Ahnstedt, Lucy Couture, Shivanki Juneja, Glenda Torres, Guadalupe J. Ortiz, James Sollome, Natalie Tabor, Bhanu P. Ganesh, H. Alex Choi, Fudong Liu, Louise D. McCullough, Andrey S. Tsvetkov
Summary: The study finds sex differences in metabolism and sexual dimorphism in the correlations between clinical parameters and metabolic profiles in severe COVID-19 patients, providing important knowledge for the development of sex-associated biomarkers and druggable targets for COVID-19 patients.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Maximilian M. Biebl, Florent Delhommel, Ofrah Faust, Krzysztof M. Zak, Ganesh Agam, Xiaoyan Guo, Moritz Muehlhofer, Vinay Dahiya, Daniela Hillebrand, Grzegorz M. Popowicz, Martin Kampmann, Don C. Lamb, Rina Rosenzweig, Michael Sattler, Johannes Buchner
Summary: In the cytosol of eukaryotic cells, the Hsp70 and Hsp90 chaperone machines work together with NudC to facilitate the maturation process of diverse client proteins. NudC acts as a transfer factor by interacting with Hsp40 and displacing Hsp70, allowing the direct transfer of Hsp40-bound client proteins to Hsp90 for further processing.
Article
Genetics & Heredity
David Conant, Tim Hsiau, Nicholas Rossi, Jennifer Oki, Travis Maures, Kelsey Waite, Joyce Yang, Sahil Joshi, Reed Kelso, Kevin Holden, Brittany L. Enzmann, Rich Stoner
Summary: ICE is a tool for analyzing CRISPR edits using Sanger data, providing a fast, accurate, and affordable way to assess the genotype after editing. It proposes potential editing outcomes and determines the data-supported results through regression analysis. ICE can analyze CRISPR experiments within days after transfection and produces accurate estimates of editing outcomes in various benchmarks and existing tools.
Article
Multidisciplinary Sciences
Alice Mac Kain, Ghizlane Maarifi, Sophie-Marie Aicher, Nathalie Arhel, Artem Baidaliuk, Sandie Munier, Flora Donati, Thomas Vallet, Quang Dinh Tran, Alexandra Hardy, Maxime Chazal, Francoise Porrot, Molly OhAinle, Jared Carlson-Stevermer, Jennifer Oki, Kevin Holden, Gert Zimmer, Etienne Simon-Loriere, Timothee Bruel, Olivier Schwartz, Sylvie van der Werf, Nolwenn Jouvenet, Sebastien Nisole, Marco Vignuzzi, Ferdinand Roesch
Summary: Researchers have identified DAXX as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells, which restricts an early step of the SARS-CoV-2 life cycle. However, SARS-CoV-2 has evolved a mechanism to counteract this inhibition by triggering the degradation of DAXX through a viral protease.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Leiping Zeng, Yanxia Liu, Xammy Huu Nguyenla, Timothy R. Abbott, Mengting Han, Yanyu Zhu, Augustine Chemparathy, Xueqiu Lin, Xinyi Chen, Haifeng Wang, Draven A. Rane, Jordan M. Spatz, Saket Jain, Arjun Rustagi, Benjamin Pinsky, Adrianna E. Zepeda, Anastasia P. Kadina, John A. Walker, Kevin Holden, Nigel Temperton, Jennifer R. Cochran, Annelise E. Barron, Michael D. Connolly, Catherine A. Blish, David B. Lewis, Sarah A. Stanley, Marie F. La Russa, Lei S. Qi
Summary: The authors demonstrate that CRISPR-Cas13d can effectively inhibit a wide range of human coronaviruses, including new SARS-CoV-2 variants, in combination with small molecule drugs. The CRISPR-Cas13d system reduces viral titers by over 99% and enhances the therapeutic effects of different antiviral drugs. Lipid nanoparticle-mediated RNA delivery enables the Cas13d system to treat infections from multiple coronavirus variants in human primary airway epithelium cultures. This study establishes CRISPR-Cas13 as a broad-spectrum antiviral strategy that complements existing vaccination and antiviral treatment strategies.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Fulong Yu, Liam D. Cato, Chen Weng, L. Alexander Liggett, Soyoung Jeon, Keren Xu, Charleston W. K. Chiang, Joseph L. Wiemels, Jonathan S. Weissman, Adam J. de Smith, Vijay G. Sankaran
Summary: Genome-wide association studies combined with single-cell genomic atlases can reveal the mechanisms of disease-causal genetic variations. However, sparse and noisy single-cell epigenomic data analysis often hinders the identification of disease-relevant cell types. To overcome this, the SCAVENGE algorithm uses network propagation to map causal variants to their relevant cellular context at a single-cell resolution, successfully identifying key biological mechanisms in various blood traits and diseases.
NATURE BIOTECHNOLOGY
(2022)
Article
Virology
Stacy Gellenoncourt, Nell Saunders, Remy Robinot, Lucas Auguste, Maaran Michael Rajah, Jerome Kervevan, Raphael Jeger-Madiot, Isabelle Staropoli, Cyril Planchais, Hugo Mouquet, Julian Buchrieser, Olivier Schwartz, Lisa A. Chakrabarti
Summary: The D614G mutation in SARS-CoV-2 stabilized the viral spike and enabled the emergence of variants with highly fusogenic spikes. The later mutations at the cleavage site further increased spike processing and fusogenicity, but limited spike incorporation into pseudoviruses. The enhanced infectivity of variants with both D614G and cleavage site mutations was more pronounced in cells with an endosomal route, suggesting a better resistance to the endosomal environment by stable spikes.
JOURNAL OF VIROLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Matthew T. N. Yarnall, Eleonora I. Ioannidi, Cian Schmitt-Ulms, Rohan N. Krajeski, Justin Lim, Lukas Villiger, Wenyuan Zhou, Kaiyi Jiang, Sofya K. Garushyants, Nathaniel Roberts, Liyang Zhang, Christopher A. Vakulskas, John A. I. I. I. I. Walker, Anastasia P. Kadina, Adrianna E. Zepeda, Kevin Holden, Hong Ma, Jun Xie, Guangping Gao, Lander Foquet, Greg Bial, Sara K. Donnelly, Yoshinari Miyata, Daniel R. Radiloff, Jordana M. Henderson, Andrew Ujita, Omar O. Abudayyeh, Jonathan S. Gootenberg
Summary: The study presents a method called PASTE, which allows programmable integration of large and diverse DNA cargo into the genome. This method successfully integrated sequences up to 36 kilobases in length at multiple genomic loci, and demonstrated activity in non-dividing cells and in vivo.
NATURE BIOTECHNOLOGY
(2023)
Article
Cell Biology
Xuming Tang, Dongxiang Xue, Tuo Zhang, Benjamin E. E. Nilsson-Payant, Lucia Carrau, Xiaohua Duan, Miriam Gordillo, Adrian Y. Y. Tan, Yunping Qiu, Jenny Xiang, Robert E. E. Schwartz, Benjamin R. R. tenOever, Todd Evans, Shuibing Chen
Summary: This study systematically examined the transcript profile changes caused by SARS-CoV-2 infection in lung airway organoids, lung alveolar organoids, and cardiomyocytes. They identified several genes, including CIART, that are involved in controlling SARS-CoV-2 infection. The researchers found that organoids and cells derived from CIART(-/-) human pluripotent stem cells were resistant to SARS-CoV-2 infection. They also discovered that CIART controls SARS-CoV-2 infection through the regulation of NR4A1, and that the Retinoid X Receptor pathway is involved in the infection process. The study highlights the role of circadian-clock regulation in SARS-CoV-2 infection and provides potential therapeutic targets for COVID-19 treatment.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lucia Carrau, Justin J. Frere, Ilona Golynker, Alvaro Fajardo, Cristobal F. Rivera, Shu Horiuchi, Tyler Roonprapunt, Judith M. Minkoff, Daniel Blanco-Melo, Benjamin TenOever
Summary: This study used a golden hamster model to investigate the dynamics between SARS-CoV-2 infection in the airways and the systemic host response. It was found that early replication of the virus occurs mainly in the respiratory tract and olfactory system, with lesser extent in the heart and gastrointestinal tract. However, a host antiviral response was observed in every organ due to the presence of circulating type I and III interferons. These findings provide insights into the diverse clinical presentations of COVID-19 and highlight the role of the respiratory tract in generating a systemic immune defense.
Article
Biochemistry & Molecular Biology
Jun-Tao Zhang, Xin-Yang Wei, Ning Cui, Ruilin Tian, Ning Jia
Summary: Zhang et al. determined multiple cryo-electron microscopy structures of inactive monomeric and active tetrameric short prokaryotic Ago/TIR-APAZ (SPARTA) complexes, providing the structural basis of SPARTA assembly and activation that will facilitate the development of SPARTA-based biotechnological tools.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Cell Biology
Kun Li, Miao Ouyang, Jiangshan Zhan, Ruilin Tian
Summary: CRISPR-Cas9-based functional genomics screening combined with hPSC differentiation technology can help us understand gene function in different human cell types and identify mechanisms and therapeutic targets for human diseases.