Article
Chemistry, Medicinal
Yu-Chi Tsai, Racheal A. Nell, Jonathan E. Buckendorf, Norbert Kusz, Peter Waweru Mwangi, Robert Berkecz, Dora Redei, Andrea Vasas, Adam M. Spivak, Judit Hohmann
Summary: Compounds from Euphorbia usambarica show potential for HIV-1 latency reversal activity, with newly discovered diterpenoids exhibiting significant improvements in activity. These natural constituents may contribute to the development of HIV-1 eradication strategies.
Article
Plant Sciences
Haitao Zhang, Jinfeng Cai, Chunna Li, Lisi Deng, Hongqiong Zhu, Ting Huang, Jiacong Zhao, Jiasheng Zhou, Kai Deng, Zhongsi Hong, Jinyu Xia
Summary: This study found that wogonin can suppress latent HIV-1 reactivation by inhibiting the expression of histone acetyltransferase p300 and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. This discovery holds promising significance for future applications in HIV-1 functional cure.
Article
Biochemistry & Molecular Biology
Haruki Kitamura, Sayaka Sukegawa, Kouki Matsuda, Kousuke Tanimoto, Takuya Kobayakawa, Kazuho Takahashi, Hirokazu Tamamura, Kiyoto Tsuchiya, Hiroyuki Gatanaga, Kenji Maeda, Hiroaki Takeuchi
Summary: Combinational antiretroviral therapy (cART) successfully suppresses viral load but fails to eliminate HIV-1 reservoirs. "Shock and Kill" strategy using latently-reversing agents (LRAs) is being developed to reactivate latent HIV-1 and induce cell death. This study identified 4-phenylquinoline-8-amine (PQA) as a novel LRA candidate that effectively reactivated HIV-1 and induced cell death in latently-infected cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Microbiology
Ariane Zutz, Lin Chen, Franziska Sippl, Andreas Humpe, Christian Schoelz
Summary: The study focused on screening latent reservoirs in HIV-1 infected individuals and identified two novel compounds with high reactivation efficiency and low toxicity as potential new treatment options for reversing latency.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Plant Sciences
Meng Wang, Zhe Zheng, Zheni Tian, Hao Zhang, Chenyu Zhu, Xiangyu Yao, Yixin Yang, Xia Cai
Summary: The function and expression regulation activities of Acetyl-CoA acetyltransferase (AACT) in Euphorbia kansui Liou (EkAACT) were investigated. The overexpression of EkAACT in Arabidopsis led to improvements in growth morphology and tolerance to abiotic stress, suggesting the crucial role of AACT in terpenoid biosynthesis and overall regulation.
Article
Virology
Emily Cruz-Lorenzo, Nora-Guadalupe P. Ramirez, Jeon Lee, Sonali Pandhe, Lei Wang, Juan Hernandez-Doria, Adam M. Spivak, Vicente Planelles, Tianna Petersen, Mamta K. Jain, Elisabeth D. Martinez, Ivan D'Orso
Summary: This study discovered a small molecule activator that alters the state of CD4(+) T cells to promote transcription and reactivation of latent HIV-1 through a unique mechanism of action. The activator triggered oxidative stress and activated a redox-responsive program involving cell-signaling kinases and atypical transcription factors, resulting in changes in viral transcriptional rewiring.
Article
Clinical Neurology
Angel Lin, Weam Othman Elbezanti, Alexis Schirling, Adel Ahmed, Rachel Van Duyne, Simon Cocklin, Zachary Klase
Summary: The HIV-1 pandemic poses a significant challenge to the field of medicine, with no cure yet found. Research has identified that the benzodiazepine Alprazolam could be an ideal candidate for latency reversal as it inhibits the transcription factor RUNX1 and increases STAT5 activation, potentially playing a positive role in addressing neuroinflammation associated with neuroHIV-1.
FRONTIERS IN NEUROLOGY
(2021)
Article
Virology
Erich J. Baker, Kelly Hughes, Tatianna Travieso, Mary E. Klotman, Maria Blasi
Summary: Anti-retroviral therapy (ART) has significantly reduced HIV-related morbidity and mortality. However, the long-term persistence of latent viral reservoirs capable of reactivation remains a challenge. This study explores the establishment of HIV-1 latency in renal epithelial cells and finds that current latency reversing agents (LRAs) have limited effectiveness in reactivating HIV-1 in these cells. Further research on LRAs in non-T cells is needed to assess their suitability for a sterilizing cure strategy.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Siyi Wang, Jianchun Li, Dan Liu, Tao Yang, Xuanqin Chen, Rongtao Li
Summary: Bioassay-guided purification of the ethanolic extract from the roots of Euphorbia kansui led to the isolation of previously unreported ingenane-type and jatrophane-type diterpenoids, as well as known diterpenoids. These compounds showed potential in reversing multidrug resistance, with particular examples demonstrating significant MDR reversal activity. This research provides new insights for the development of MDR regulatory agents.
Article
Virology
Michelle E. Wong, Chad J. Johnson, Anna C. Hearps, Anthony Jaworowski
Summary: In this study, a robust experimental model was established to quantify and investigate HIV reactivation in latently infected macrophages, showing that different macrophage phenotypes, cellular and tissue environments influence HIV reactivation. Additionally, the study demonstrated that certain latency-reversing agents may have different effects on latently infected macrophages compared to T cells, suggesting the need for dedicated strategies to target these populations in vivo.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Terry L. Hafer, Abby Felton, Yennifer Delgado, Harini Srinivasan, Michael Emerman
Summary: This study aimed to investigate whether host factors required for HIV-1 replication also play a role in latency reversal. By using a CRISPR gene library and analyzing RNA sequencing data, several key HIV-1 dependency factors were identified, with CCNT1 being the most crucial factor for latency reactivation.
Article
Plant Sciences
Reham Hammadi, Norbert Kusz, Csilla Zsuzsanna David, Zoltan Behany, Laszlo Papp, Lajos Kemeny, Judit Hohmann, Lorant Lakatos, Andrea Vasas
Summary: Research on other Euphorbia species has identified structurally similar diterpenoids with stronger cytotoxic activity in vitro, potentially serving as alternatives to ingenol mebutate.
Article
Biochemistry & Molecular Biology
Ye Zhao, Chen Hua, Yi-ou Sha, Pei-Qian Wu, Qun-Fang Liu, Lu Lu, Bin Zhou, Shi-bo Jiang, Yao-Yue Fan, Jian-Min Yue
Summary: Nine undiscovered diterpenoids, including four ingol-type and five ent-pimarane-type compounds, were identified from the leaves and stems of Euphorbia lactea Haw. The structures and configurations of compounds 1-9 were determined through spectroscopic analysis, ECD calculations, and X-ray diffraction. Compounds 3 and 16 exhibited anti-HIV-1 activity with IC50 values of 1.17 μM (SI=16.54) and 13.10 μM (SI=1.93), respectively.
Article
Biochemistry & Molecular Biology
Jian-Chun Li, Shu-Yi Li, Jian-Xian Tang, Dan Liu, Xiao-Yi Feng, Kai-Rui Rao, Xu-Dong Zhao, Hong-Mei Li, Rong-Tao Li
Summary: Six undescribed triterpenoids and two undescribed C21-steroidal glycosides, along with fifty-four known compounds, were isolated from the roots of Euphorbia kansui. The structures of these compounds were determined through spectroscopic analysis, and the absolute configuration of one compound was elucidated using ECD calculation. These compounds exhibited various biological activities, including inhibition of nitric oxide production and cytotoxicity against cancer cell lines. Importantly, a compound called euphol showed selective inhibition against human glioma stem cells.
Article
Virology
Kelly S. Harrison, Nishani Wijesekera, Anastasia G. J. Robinson, Vanessa C. Santos, Robert H. Oakley, John A. Cidlowski, Clinton Jones
Summary: This study suggests that female mice expressing GR(S229A) have significantly lower levels of infectious virus during explant-induced reactivation compared to male GR(S229A) or wild-type mice. Furthermore, female GR(S229A) mice have fewer VP16 + TG neurons during the early stages of explant-induced reactivation, indicating that GR transcriptional activity has female-specific effects.
JOURNAL OF VIROLOGY
(2023)
Article
Microbiology
Gabriele Cerutti, Yicheng Guo, Tongqing Zhou, Jason Gorman, Myungjin Lee, Micah Rapp, Eswar R. Reddem, Jian Yu, Fabiana Bahna, Jude Bimela, Yaoxing Huang, Phinikoula S. Katsamba, Lihong Liu, Manoj S. Nair, Reda Rawi, Adam S. Olia, Pengfei Wang, Baoshan Zhang, Gwo-Yu Chuang, David D. Ho, Zizhang Sheng, Peter D. Kwong, Lawrence Shapiro
Summary: Structural analysis revealed that seven potent NTD-directed neutralizing antibodies target a common surface on NTD, forming a single supersite different from the recognition pattern of RBD-directed antibodies.
CELL HOST & MICROBE
(2021)
Article
Multidisciplinary Sciences
Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, Christos A. Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D. Ho
Summary: The COVID-19 pandemic has had global repercussions, with promising vaccines and monoclonal antibody therapies. However, newly detected variants of SARS-CoV-2 present challenges to these treatment options.
Article
Cardiac & Cardiovascular Systems
Liuliu Yang, Yuling Han, Fabrice Jaffre, Benjamin E. Nilsson-Payant, Yaron Bram, Pengfei Wang, Jiajun Zhu, Tuo Zhang, David Redmond, Sean Houghton, Skyler Uhl, Alain Borczuk, Yaoxing Huang, Chanel Richardson, Vasuretha Chandar, Joshua A. Acklin, Jean K. Lim, Zhengming Chen, Jenny Xiang, David D. Ho, Benjamin R. tenOever, Robert E. Schwartz, Todd Evans, Shuibing Chen
Summary: Cardiac complications in COVID-19 patients are commonly associated with macrophage-mediated inflammation. The study established an immunocardiac coculture platform to model this inflammation, identifying potential drug candidates like ranolazine and tofacitinib that protect cardiomyocytes from macrophage-induced damage.
CIRCULATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Alberto Bartolome, Jiani Liang, Pengfei Wang, David D. Ho, Utpal B. Pajvani
Summary: ACE2 is both a key regulator of the renin-angiotensin system and the functional receptor of SARS-CoV-2. Research suggests that it may be affected by gamma S proteolytic activity, leading to a novel pathway for cellular ACE2 trafficking.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Micah Rapp, Yicheng Guo, Eswar R. Reddem, Jian Yu, Lihong Liu, Pengfei Wang, Gabriele Cerutti, Phinikoula Katsamba, Jude S. Bimela, Fabiana A. Bahna, Seetha M. Mannepalli, Baoshan Zhang, Peter D. Kwong, Yaoxing Huang, David D. Ho, Lawrence Shapiro, Zizhang Sheng
Summary: Antibodies derived from the VH1-2 gene have been shown to be potent neutralizing antibodies against SARS-CoV-2, with three VH1-2-derived antibodies (2-15, 2-43, and H4) using VH1-2-encoded motifs to recognize the receptor-binding domain (RBD) of the virus spike protein. Despite genetic similarities, these antibodies are able to recognize both up and down conformations of the RBD, with some antibodies using elongated CDRH3s to interact with glycan N343 on a neighboring RBD. The VH1-2 antibody class utilizes modular genetic elements for modular recognition, with VH gene specifying RBD recognition and CDRH3 specifying quaternary interactions.
Article
Engineering, Chemical
Bharat Madan, Eswar R. Reddem, Pengfei Wang, Ryan G. Casner, Manoj S. Nair, Yaoxing Huang, Ahmed S. Fahad, Matheus Oliveira de Souza, Bailey B. Banach, Sheila N. Lopez Acevedo, Xiaoli Pan, Rajani Nimrania, I-Ting Teng, Fabiana Bahna, Tongqing Zhou, Baoshan Zhang, Michael T. Yin, David D. Ho, Peter D. Kwong, Lawrence Shapiro, Brandon J. DeKosky
Summary: Screening for anti-SARS-CoV-2 mAbs at reduced pH can lead to more efficient neutralizing antibody discovery, and a potent new antibody LP5 targets the SARS-CoV-2 N-terminal domain via a unique binding recognition mode.
Article
Multidisciplinary Sciences
Medini K. Annavajhala, Hiroshi Mohri, Pengfei Wang, Manoj Nair, Jason E. Zucker, Zizhang Sheng, Angela Gomez-Simmonds, Anne L. Kelley, Maya Tagliavia, Yaoxing Huang, Trevor Bedford, David D. Ho, Anne-Catrin Uhlemann
Summary: The emergence of the B.1.526 lineage of SARS-CoV-2, with mutations such as E484K, has led to its rapid dominance in New York City. This variant is resistant to therapeutic monoclonal antibodies and less susceptible to neutralization by antibodies from recovered or vaccinated individuals, contributing to its fast spread.
Article
Multidisciplinary Sciences
Jianliang Xu, Kai Xu, Seolkyoung Jung, Andrea Conte, Jenna Lieberman, Frauke Muecksch, Julio Cesar Cetrulo Lorenzi, Solji Park, Fabian Schmidt, Zijun Wang, Yaoxing Huang, Yang Luo, Manoj S. Nair, Pengfei Wang, Jonathan E. Schulz, Lino Tessarollo, Tatsiana Bylund, Gwo-Yu Chuang, Adam S. Olia, Tyler Stephens, I-Ting Teng, Yaroslav Tsybovsky, Tongqing Zhou, Vincent Munster, David D. Ho, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig, Peter D. Kwong, Rafael Casellas
Summary: The study found that camelid nanobodies can effectively circumvent vaccine escape caused by mutations in the novel coronavirus. These nanobodies are able to neutralize SARS-CoV-2 variants through two mechanisms, demonstrating promising potential in preventing COVID-19 mortality when vaccines are compromised.
Article
Cell Biology
Xiaohua Duan, Xuming Tang, Manoj S. Nair, Tuo Zhang, Yunping Qiu, Wei Zhang, Pengfei Wang, Yaoxing Huang, Jenny Xiang, Hui Wang, Robert E. Schwartz, David D. Ho, Todd Evans, Shuibing Chen
Summary: Developing disease models to study SARS-CoV-2 infection is crucial, and research using airway organoids derived from human pluripotent stem cells has identified compounds that can block the virus. Further investigation reveals that these compounds inhibit SARS-CoV-2 infection by targeting the HIF1a-glycolysis axis.
Article
Immunology
Pengfei Wang, Ryan G. Casner, Manoj S. Nair, Jian Yu, Yicheng Guo, Maple Wang, Jasper F-W Chan, Gabriele Cerutti, Sho Iketani, Lihong Liu, Zizhang Sheng, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Yaoxing Huang, Lawrence Shapiro, David D. Ho
Summary: The development of potent and broad-spectrum antiviral therapeutics and vaccines is crucial in dealing with highly pathogenic human coronaviruses and their evolving variants. Monoclonal antibody 2-36, isolated from COVID-19-convalescent patients, has been found to cross-neutralize SARS-CoV and other coronaviruses. The cryo-EM structure of 2-36 with SARS-CoV-2 and SARS-CoV spike reveals a conserved epitope in the receptor-binding domain (RBD). This antibody can neutralize various SARS-CoV-2 variants, as well as bat and pangolin sarbecoviruses that use human ACE2 as a receptor.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Immunology
Xun Wang, Xiaoyu Zhao, Jieyu Song, Jing Wu, Yuqi Zhu, Minghui Li, Yuchen Cui, Yanjia Chen, Lulu Yang, Jun Liu, Huanzhang Zhu, Shibo Jiang, Pengfei Wang
Summary: This study found that the Omicron variant is highly resistant to neutralization by sera from convalescents or individuals vaccinated with two doses of inactivated whole-virion vaccines. However, a homologous or heterologous booster significantly increased neutralization titers. Additionally, the Omicron variant resists most monoclonal antibodies targeting distinct epitopes. These findings highlight the importance of pushing forward booster vaccinations to combat emerging SARS-CoV-2 variants.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Microbiology
Jingwen Ai, Xun Wang, Xinyi He, Xiaoyu Zhao, Yi Zhang, Yuchao Jiang, Minghui Li, Yuchen Cui, Yanjia Chen, Rui Qiao, Lin Li, Lulu Yang, Yi Li, Zixin Hu, Wenhong Zhang, Pengfei Wang
Summary: This study compared the neutralization efficacy of vaccine-induced or monoclonal antibodies against different sub-lineages of the Omicron variant. The results showed that current vaccines have low neutralization activity, but both homologous and heterologous boosters significantly improved neutralization titers. The study also found that most monoclonal antibodies lost their neutralizing activity, while some demonstrated distinct neutralization patterns among Omicron sub-lineages, indicating antigenic differences.
CELL HOST & MICROBE
(2022)
Review
Microbiology
Hao Zhou, Michelle Mohlenberg, Jigarji C. Thakor, Hardeep Singh Tuli, Pengfei Wang, Yehuda G. Assaraf, Kuldeep Dhama, Shibo Jiang
Summary: The SARS-CoV-2 virus is continuously evolving and mutating, with the emergence of the highly mutated and transmissible Omicron variant. This variant evades protection from vaccines and antibody-based therapies, but is sensitive to certain antiviral drugs. Understanding the virology and immune mechanisms of the Omicron variant is crucial for developing effective vaccines and treatments.
CLINICAL MICROBIOLOGY REVIEWS
(2022)
Article
Microbiology
Xun Wang, Minghui Li, Panpan Lu, Chen Li, Chaoyue Zhao, Xiaoyu Zhao, Rui Qiao, Yuchen Cui, Yanjia Chen, Jiayan Li, Guonan Cai, Pengfei Wang
Summary: There are concerns about the safety of SARS-CoV-2 vaccines and antibody therapeutics due to evidence of antibody-dependent enhancement (ADE) of other viruses. In this study, it was found that vaccination/convalescent sera and certain monoclonal antibodies can enhance SARS-CoV-2 infection in vitro. However, this enhancement can be prevented by blocking the interaction between antibodies and receptors.
Article
Multidisciplinary Sciences
Yuling Han, Xiaohua Duan, Liuliu Yang, Benjamin E. Nilsson-Payant, Pengfei Wang, Fuyu Duan, Xuming Tang, Tomer M. Yaron, Tuo Zhang, Skyler Uhl, Yaron Bram, Chanel Richardson, Jiajun Zhu, Zeping Zhao, David Redmond, Sean Houghton, Duc-Huy T. Nguyen, Dong Xu, Xing Wang, Jose Jessurun, Alain Borczuk, Yaoxing Huang, Jared L. Johnson, Yuru Liu, Jenny Xiang, Hui Wang, Lewis C. Cantley, Benjamin R. TenOever, David D. Ho, Fong Cheng Pan, Todd Evans, Huanhuan Joyce Chen, Robert E. Schwartz, Shuibing Chen
Summary: Researchers have developed lung and colonic organoid models using human pluripotent stem cells, which demonstrate susceptibility to SARS-CoV-2 infection. These models are valuable for studying the infection of the virus and screening drugs, with potential therapeutic implications for COVID-19.