Article
Pharmacology & Pharmacy
Lindsay F. Kramzer, Krystal T. Hamorsky, Phillip W. Graebing, Lin Wang, Joshua L. Fuqua, Nobuyuki Matoba, Amanda B. Lasnik, Bernard J. Moncla, Junmei Zhang, Kenneth E. Palmer, Lisa C. Rohan
Summary: GRFT shows potent anti-HIV activity and promising potential as a drug candidate for HIV prevention. Preformulation assessments reveal its safety and stability under most conditions, but susceptibility to oxidative degradation requires effective protection for further development.
Article
Biochemistry & Molecular Biology
Jiadong Sun, Gengxiang Zhao, Tatsiana Bylund, Myungjin Lee, Srikar Adibhatla, Peter D. Kwong, Gwo-Yu Chuang, Reda Rawi, Carole A. Bewley
Summary: Lectins, such as the therapeutic lectin griffithsin (GRFT), have the potential to bind to carbohydrates and glycan shields, making them promising for therapeutic and diagnostic applications. By studying the structure and activity of GRFT, researchers have identified a critical core structure that is important for antiviral activity and binding to high mannose glycans. This discovery may help in designing carbohydrate receptors and improving the affinity and stability of known lectins.
ACS CHEMICAL BIOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Farnaz Minooei, Joel R. Fried, Joshua L. Fuqua, Kenneth E. Palmer, Jill M. Steinbach-Rankins
Summary: Co-administration of the oxidation-resistant variant griffithsin (Q-GRFT) with antiretrovirals (ARVs) in free or encapsulated forms may improve efficacy in achieving prophylaxis, showing synergistic interactions in in vitro assays.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(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
Biochemistry & Molecular Biology
Althea Gaffney, Aakansha Nangarlia, Charles G. Ang, Steven Gossert, Adel Ahmed Rashad Ahmed, Md Alamgir Hossain, Cameron F. Abrams, Amos B. Smith, Irwin Chaiken
Summary: A strategy has been developed to synthesize a family of bifunctional HIV-1 inhibitor covalent conjugates capable of binding to both gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex. These conjugates showed potent virus inhibition and virion lysis in vitro, suggesting potential for eliminating Env-expressing infected cells and eradicating HIV-1.
ACS CHEMICAL BIOLOGY
(2021)
Review
Microbiology
Jean-Francois Bruxelle, Nino Trattnig, Marianne W. Mureithi, Elise Landais, Ralph Pantophlet
Summary: This review discusses the challenges in developing effective strategies to prevent HIV-1 infection based on insights from the current model of mucosal transmission and cell entry. It examines key viral and host factors, preventive strategies using antibody-mediated protection against T/F viruses and mucosal immunity, and treatment strategies targeting viral entry with a focus on clinically advanced entry inhibitors.
Article
Virology
Saumya Anang, Jonathan Richard, Catherine Bourassa, Guillaume Goyette, Ta-Jung Chiu, Hung-Ching Chen, Amos B. Smith, Navid Madani, Andres Finzi, Joseph Sodroski
Summary: This study identifies pathways whereby HIV-1 can develop resistance to CD4-mimetic compounds and conformational blockers. The findings provide guidance for improving the potency and breadth of small-molecule HIV-1 entry inhibitors.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Yajing Zhao, Ningbo Zhao, Yanxing Cai, Hui Zhang, Jia Li, Jiaqi Liu, Chuantao Ye, Yuan Wang, Yamei Dang, Wanying Li, He Liu, Lianqing Zhang, Yuexiang Li, Liang Zhang, Linfeng Cheng, Yangchao Dong, Zhikai Xu, Yingfeng Lei, Lu Lu, Yingjuan Wang, Wei Ye, Fanglin Zhang
Summary: The study discovered that griffithsin can effectively inhibit the growth and spread of Hantaan virus. In vitro experiments demonstrate that griffithsin can prevent the entry of the virus into host cells, and in vivo experiments showed partial protection of mice from Hantaan virus-induced death.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Donna L. Mallery, Alex B. Kleinpeter, Nadine Renner, K. M. Rifat Faysal, Mariia Novikova, Leo Kiss, Miranda S. C. Wilson, Bilal Ahsan, Zunlong Ke, John A. G. Briggs, Adolfo Saiardi, Till Bocking, Eric O. Freed, Leo C. James
Summary: HIV maintains immature lattice stability to ensure IP6 packaging while allowing maturation. Mutant viruses with reduced IP6 recruitment show increased infectivity upon treatment with MIs or second-site compensatory mutations.
Article
Cell Biology
Paul Lopez, Oluwaseun Ajibola, Amelie Pagliuzza, Romaniya Zayats, Wan Hon Koh, Alon Herschhorn, Nicolas Chomont, Thomas T. Murooka
Summary: The migration of T cells in 3D collagen matrix enhances HIV infection and integration. Migratory T cells are less sensitive to antiretroviral drugs and can freely migrate into regions with high HIV densities, resulting in high infection rates. These findings indicate that the environmental context of initial HIV-T cell encounters modulates HIV-1 entry and integration efficiencies.
Article
Cell Biology
Belinda L. Spillings, Christopher J. Day, Albert Garcia-Minambres, Anupriya Aggarwal, Nicholas D. Condon, Thomas Haselhorst, Damian F. J. Purcell, Stuart G. Turville, Jennifer L. Stow, Michael P. Jennings, Johnson Mak
Summary: This study reveals that HIV is captured near the lymphocyte surface in a virion-glycan-dependent manner. Removing certain glycans impairs virus-cell binding and interfering with glycan interactions reduces HIV infectivity. These findings provide new insights into the interaction between HIV and host cells.
Article
Chemistry, Medicinal
Natalie Losada, Francesc X. Ruiz, Francesca Curreli, Kevin Gruber, Alyssa Pilch, Kalyan Das, Asim K. Debnath, Eddy Arnold
Summary: This study focuses on compounds (NBD derivatives) originally developed to bind to HIV-1 gp120, some of which inhibit RT. Crystal structures of three NBD compounds in complex with HIV-1 RT have been determined, correlating with RT enzyme inhibition and antiviral activity, to develop structure-activity relationships. Two lead compounds, NBD-14189 and NBD-14270, show potent antiviral activity and low cytotoxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Nikhil Seval, Cynthia Frank, Michael Kozal
Summary: Fostemsavir, the first attachment inhibitor approved by the FDA, shows good tolerability and efficacy in heavily treatment experienced HIV patients, with potential as an important advancement for patients with drug-resistant HIV.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2021)
Article
Microbiology
Gregory A. Sowd, Christopher Aiken
Summary: Our study demonstrates that inositol phosphates, IP5 and IP6, play crucial roles in HIV-1 assembly and maturation. Depletion of IP5 and IP6 in T cells resulted in impaired viral particle assembly and reduced infectivity of produced virions. These findings suggest that targeting HIV-1 inositol phosphate binding pockets may inhibit distinct aspects of HIV-1 replication.
Article
Chemistry, Multidisciplinary
Alessia Amodio, Marco Cassani, Liviana Mummolo, Christina Cortez-Jugo, Sukhvir Kaur Bhangu, Jori Symons, Chantelle L. Ahlenstiel, Giancarlo Forte, Francesco Ricci, Anthony D. Kelleher, Sharon R. Lewin, Francesca Cavalieri, Frank Caruso
Summary: This study develops a strategy combining DNA nanotechnology and super-resolution expansion microscopy (ExM) to detect and image HIV-1 RNA in infected cells. By using a chimeric locked nucleic acid (LNA)-DNA sensor and physically trapping the viral RNA, nanoscale imaging is achieved.