Article
Biochemistry & Molecular Biology
Mastaneh Safarnejad Shad, Sandra Claes, Eline Goffin, Tom Van Loy, Dominique Schols, Steven De Jonghe, Wim Dehaen
Summary: The expansion of the structure-activity relationship study of CXCR4 antagonists led to the synthesis of a series of isoquinolines with excellent activity, among which compound 24c showed consistently low nanomolar activity in various assays and was deemed the most promising.
Article
Virology
Julio C. C. Lorenzi, Pilar Mendoza, Yehuda Z. Cohen, Lilian Nogueira, Christy Lavine, Joseph Sapiente, Marie Wiatr, Nelly R. Mugo, Andrew Mujugira, Sinead Delany, Jairam Lingappa, Connie Celum, Michael S. Seaman, Marina Caskey, Michel C. Nussenzweig
Summary: This study examined the neutralizing activity of 9 anti-HIV-1 bNAbs against primary African isolates, finding that the potency and breadth of bNAbs were significantly lower than what was seen with pseudotyped virus panels. The differences in sensitivity between pseudotyped viruses and primary isolates varied depending on the bNAb and the HIV-1 Glade.
JOURNAL OF VIROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Takuya Kobayakawa, Masaru Yokoyama, Kohei Tsuji, Masayuki Fujino, Masaki Kurakami, Takato Onishi, Sayaka Boku, Takahiro Ishii, Yutaro Miura, Kouki Shinohara, Yuki Kishihara, Nami Ohashi, Osamu Kotani, Tsutomu Murakami, Hironori Sato, Hirokazu Tamamura
Summary: The HIV-1 capsid is crucial for viral replication and represents a potential target for antiviral drugs. A small molecule designed to mimic the interaction between CA proteins has shown significant anti-HIV-1 activity. In this study, molecules with different structures based on this small molecule were synthesized and found to have significant anti-HIV activity, with advantages over previous compounds.
Article
Chemistry, Medicinal
Iris Cadima-Couto, Alexandra Tauzin, Joao M. Freire, Tiago N. Figueira, Ruben D. M. Silva, Clara Perez-Peinado, Catarina Cunha-Santos, Ines Bartolo, Nuno Taveira, Lurdes Gano, Joao D. G. Correia, Joao Goncalves, Fabrizio Mammano, David Andreu, Miguel A. R. B. Castanho, Ana Salome Veiga
Summary: The anti-HIV-1 peptide pepRF1, derived from the Dengue virus capsid protein, shows promising inhibitory effects with a potential therapeutic window higher than 53,000. It specifically targets CXCR4-tropic strains, preventing viral entry into target cells by acting as an antagonist of the viral coreceptor CXCR4. Compared to T20, a peptide-based HIV-1 entry inhibitor, pepRF1 is more effective and can potentially be used alone or in combination with other anti-HIV drugs, as well as a novel therapeutic strategy for other CXCR4-related diseases.
ACS INFECTIOUS DISEASES
(2021)
Article
Chemistry, Multidisciplinary
Dipankar Chaudhuri, Tiangong Lu, Binu Jacob, Sojan Abraham, Premlata Shankar, Michael A. Poss, Nouri Neamati, Julio A. Camarero
Summary: The CXCR4 chemokine is a crucial regulator of leukocyte functions, embryonic development, and cancer progression. CXCR4 antagonists show promise as therapeutic agents for cancer and HIV. This study shows that lipidation can improve the half-life of a bioactive cyclotide antagonist, but the choice of lipid may affect its biological activity.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Virology
Hui Li, Shuyi Wang, Fang-Hua Lee, Ryan S. Roark, Alex Murphy, Jessica Smith, Chengyan Zhao, Juliette Rando, Neha Chohan, Yu Ding, Eunlim Kim, Emily Lindemuth, Katharine J. Bar, Ivona Pandrea, Cristian Apetrei, Brandon F. Keele, Jeffrey D. Lifson, Mark G. Lewis, Thomas N. Denny, Barton F. Haynes, Beatrice H. Hahn, George M. Shaw
Summary: The study demonstrates the successful construction of SHIVs with bulky aromatic substitutions at residue 375, allowing efficient replication in rhesus macaques and effective transmission across rectal, vaginal, penile, oral, or intravenous routes. These SHIVs can serve as a model for HIV-1 infection studies in preclinical monkey trials.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemical Research Methods
Maria J. Gomara, Ramon Pons, Carolina Herrera, Paul Ziprin, Isabel Haro
Summary: A novel peptide amphiphile (PA) based on the E1P47 peptide sequence was designed and synthesized in this study to target lipid rafts of the cell membrane, demonstrating potential antiviral activity against HIV-1. The length of the polyethylene glycol spacer, the position of peptide conjugation, and the type of hydrophobic residue were found to affect the antiviral efficacy of the construct, with monoalkyl PAs showing the highest anti-HIV-1 activities in cellular and preclinical models.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Microbiology
Olga Vladimirovna Orlova, Dina Viktorovna Glazkova, Ramil Rafailovich Mintaev, Galina Mikhailovna Tsyganova, Felix Anatolevich Urusov, German Alexandrovich Shipulin, Elena Vladimirovna Bogoslovskaya
Summary: A promising gene therapy approach for treating HIV infection involves inserting antiviral genes into host cells to inhibit HIV replication. Six constructs of lentiviral vectors containing different arrangements of three antiviral genes were obtained. These vectors varied in titer production and had different effects on cell viability, transduction efficiency, and expression stability. Three of the six vectors, which showed stable expression, were compared for their antiviral activity using the SupT1 cell line, and all of them provided protection against HIV infection.
Article
Chemistry, Medicinal
Lina Zhang, Fenju Wei, David Borrego, Fabao Zhao, Javier Martinez del Rio, Estrella Frutos-Beltran, Jiwei Zhang, Shujing Xu, Nerea Lopez-Carrobles, Shenghua Gao, Dongwei Kang, Christophe Pannecouque, Erik De Clercq, Xinyong Liu, Luis Menendez-Arias, Peng Zhan
Summary: This study reports a series of improved RNase H inhibitors derived from II-25, with IA-6 being the most potent compound showing strong HIV-1 RNase H inhibitory activity. However, these compounds did not exhibit significant antiviral activity in cell culture. The low cytotoxicity of these compounds confirms the importance of identifying galloyl derivatives as valuable leads for further optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Andrei Siniavin, Svetlana Grinkina, Alexey Osipov, Vladislav Starkov, Victor Tsetlin, Yuri Utkin
Summary: Earlier studies have shown that PLA2 from bee and snake venoms can block HIV replication, and now it is found that snake PLA2s have similar antiviral activity against HIV as mammalian PLA2. Only dimeric PLA2s with catalytic activity have pronounced virucidal and anti-HIV effects. Snake PLA2s may be considered as candidate molecules for anti-HIV drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Diogo A. Mendonca, Mariet Bakker, Christine Cruz-Oliveira, Vera Neves, Maria Angeles Jimenez, Sira Defaus, Marco Cavaco, Ana Salome Veiga, Iris Cadima-Couto, Miguel A. R. B. Castanho, David Andreu, Toni Todorovski
Summary: Passing through the blood-brain barrier to treat neurological conditions is a major challenge in modern medicine, and peptide-drug conjugates (PDCs) are seen as a promising therapeutic strategy, particularly for viral neurological disorders.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Microbiology
Ole Lagatie, Dax Lauwers, Harvinder Singh, Fien Vanroye, Daniel J. Stieh, Johan Vingerhoets, Ludo Lavreys, Valerie Oriol-Mathieu, Will Colon, Chris Verhofstede, Koen Vercauteren, Dorien Van den Bossche, Maria Grazia Pau
Summary: The use of current serological tests may pose challenges to the adoption of HIV vaccines due to the overlap between HIV antigens detected in these tests and those used in the vaccines. Our study aimed to identify target antigens that can be used in new serological tests to accurately diagnose HIV infections without interference from vaccine-induced antibodies.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Jennillee Wallace, Hemil Gonzalez, Reshma Rajan, Srinivas D. Narasipura, Amber K. Virdi, Arnold Z. Olali, Ankur Naqib, Zarema Arbieva, Mark Maienschein-Cline, Lena Al-Harthi
Summary: Combination antiretroviral therapy (cART) has significantly improved the treatment of HIV/AIDS, but it may also affect cell dysregulation and increase susceptibility to comorbidities in persons living with HIV (PLWH).
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Simin Emamzadeh Yazdi, Heino Martin Heyman, Gerhard Prinsloo, Thomas Klimkait, Jacobus Johannes Marion Meyer
Summary: This study identified biomarkers for anti-HIV activity in Helichrysum species using metabolomics, and revealed the differences in chemical composition associated with anti-HIV activity.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Virology
Rui Yuan, Yongxi Zhang, Liping Deng, Xingxia Yu, Ke Zhuang, Xiaoping Chen, Qian Cao, Haiqin Ping, Hengning Ke, Xien Gui, Rongrong Yang
Summary: This study aimed to establish a plasma model to predict liver fibrosis risk in HIV/HBV co-infected individuals. By using quantitative liquid chromatography-tandem mass spectrometry, differentially expressed proteins (DEPs) in plasma were identified. A total of 97 DEPs were identified, among which 11 were validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. These DEPs were found to mediate various pathophysiological pathways, and a logistic model was established to predict liver fibrosis, incorporating immunoglobulin heavy variable 3-20, immunoglobulin heavy variable 1-24, and macrophage colony-stimulating factor 1 receptor proteins. Further validation is needed for this model.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Microbiology
Sara Rodriguez-Mora, Flore De Witid, Javier Garcia-Perez, Mercedes Bermejo, Maria Rosa Lopez-Huertas, Elena Mateos, Pilar Marti, Susana Rocha, Lorena Vigon, Frauke Christ, Zeger Debyser, Juan Jesus Vilchez, Mayte Coiras, Jose Alcami
Article
Virology
Irena Zurnic Bonisch, Lieve Dirix, Veerle Lemmens, Doortje Borrenberghs, Flore De Wit, Frank Vernaillen, Susana Rocha, Frauke Christ, Jelle Hendrix, Johan Hofkens, Zeger Debyser
JOURNAL OF VIROLOGY
(2020)
Article
Cell Biology
Marjolein Ensinck, Liesbeth De Keersmaecker, Lise Heylen, Anabela S. Ramalho, Rik Gijsbers, Ricard Farre, Kris De Boeck, Frauke Christ, Zeger Debyser, Marianne S. Carlon
Article
Biochemistry & Molecular Biology
Gerlinde Vansant, Heng-Chang Chen, Eduard Zorita, Katerina Trejbalova, Dalibor Miklik, Guillaume Filion, Zeger Debyser
NUCLEIC ACIDS RESEARCH
(2020)
Article
Cell Biology
Siska Van Belle, Sara El Ashkar, Katerina Cermakova, Filip Matthijssens, Steven Goossens, Alessandro Canella, Courtney H. Hodges, Frauke Christ, Jan De Rijck, Pieter Van Vlierberghe, Vaclav Veverka, Zeger Debyser
Summary: HDGF-related protein 2 (HRP-2) plays an important role in MLL rearranged leukemia, but unlike LEDGF/p75, it is more critical for the survival of leukemic cells rather than the transformation of MLL-ENL leukemogenesis.
Article
Microbiology
Anne Bruggemans, Gerlinde Vansant, Mini Balakrishnan, Michael L. Mitchell, Ruby Cai, Frauke Christ, Zeger Debyser
Summary: LEDGINs are potent antivirals that inhibit HIV integration and maturation, as well as redirect residual integrants to a repressive chromatin environment. The study compared the potent, preclinical lead compound GS-9822 with CX14442 in terms of antiviral potency, integration site selection, latency, and reactivation, demonstrating the potential of GS-9822 as a preclinical candidate for future functional cure research.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biotechnology & Applied Microbiology
Alessandro Canella, Siska Van Belle, Tine Brouns, Giovanni Nigita, Marianne S. Carlon, Frauke Christ, Zeger Debyser
Summary: LEDGF/p75 plays a crucial role in leukemogenesis in MLL, as well as in cancer survival, stem cell renewal, and activation of nuclear super enhancers.
CANCER GENE THERAPY
(2022)
Review
Virology
Maryam Tabasi, Ivan Nombela, Julie Janssens, Adrien P. Lahousse, Frauke Christ, Zeger Debyser
Summary: Understanding the interactions between viral proteins and host proteins is crucial for studying the pathogenesis of HIV and developing antiviral therapies. The steps of HIV-1 uncoating and nuclear import remain highly debated, with controversies surrounding the viral and host factors involved in these processes. The role of transportin-SR2 as a host cell factor in active nuclear transport is comprehensively discussed in this review.
Article
Chemistry, Multidisciplinary
Rajasekaran Ganesan, Mansour A. Dughbaj, Lisa Ramirez, Steven Beringer, Teshome L. Aboye, Alexander Shekhtman, Paul M. Beringer, Julio A. Camarero
Summary: This study reports the development of a novel engineered cyclotide with effective broad-spectrum antibacterial activity against several ESKAPE bacterial strains and clinical isolates. The most active antibacterial cyclotide was extremely stable in serum, showed little hemolytic activity, and provided protection in vivo in a murine model of P. aeruginosa peritonitis. These results highlight the potential of the cyclotide scaffold for the development of novel antimicrobial therapeutic leads for the treatment of bacteremia.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Dipankar Chaudhuri, Rajasekaran Ganesan, Alicia Vogelaar, Mansour A. Dughbaj, Paul M. Beringer, Julio A. Camarero
Summary: A new epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation and desulfurization reaction has been developed, resulting in a high yield of bioactive murepavadin in two steps. The synthetic peptide antibiotic showed potent activity against different clinical isolates of P. aeruginosa. This approach can be easily adapted for the production of murepavadin analogues and other backbone-cyclized peptides.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Subhabrata Majumder, Deep S. Bhattacharya, Alex Langford, Arun Alphonse Ignatius
Summary: In this study, the viscosity behavior of a set of Pfizer mAbs was correlated using Dynamic Light Scattering (DLS) and 2D NMR based methyl fingerprinting. Methyl fingerprinting allowed for differentiation of viscosity prone mAbs from well behaved ones even at high concentrations. The study provides important insights for stability, processing, and drug product development of therapeutic monoclonal antibodies.
PHARMACEUTICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Aline Acke, Siska Van Belle, Boris Louis, Raffaele Vitale, Susana Rocha, Thierry Voet, Zeger Debyser, Johan Hofkens
Summary: Interactions between epigenetic readers and histone modifications are crucial in gene expression regulation. We have developed a method called Expansion Microscopy for Epigenetics (ExEpi) that preserves spatial information and improves resolution, allowing the study of epigenetic interactions and drug discovery.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Julie Janssens, Flore De Wit, Nagma Parveen, Zeger Debyser
Summary: Current antiretroviral treatment is unable to cure HIV-1 infection, as the virus can hide in cellular reservoirs and rebound after therapy is discontinued. This study investigates the impact of LEDGINs on the location, transcription, and reactivation of HIV-1. The results suggest that LEDGIN-mediated retargeting can hinder viral transcription and lead to an enrichment of provirus in deep latency. These findings have implications for the development of functional cure strategies for HIV-1.
Review
Virology
Eline Pellaers, Anayat Bhat, Frauke Christ, Zeger Debyser
Summary: To complete replication, retroviruses integrate their RNA genome into a host chromosome by selecting specific integration sites. These integration sites play important roles in retroviral replication, oncogenesis, and latency. This review summarizes the mechanisms underlying integration site selection in gammaretrovirus MLV and lentivirus HIV-1 and discusses how understanding these mechanisms can contribute to the development of safer viral vectors for gene therapy and potentially lead to a cure for HIV-1 infection.
Article
Chemistry, Multidisciplinary
Rachayita Nag, Srishti Joshi, Anurag Singh Rathore, Subhabrata Majumder
Summary: In this study, the activity of L-asparaginase II (MW 135 kDa) from E. coli was observed using NMR technology. It was found that a flexible loop structure of the enzyme played a key role in its activity. Combining isothermal titration calorimetry (ITC) and NMR, it was demonstrated that changes in protein conformation could result in loss of function. The results indicate that 2D NMR can be reliably used to evaluate the structure-function relationship of this enzyme without the need for protein labeling.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
