Carboxyamidotriazole

The HIV-1 capsid protein (CA) is essential for viral replication and serves as a validated antiviral drug target. Traditional purification of CA relies on multi-step chromatographic protocols, which are time-consuming and labor-intensive. In this study, we established a rapid, column-free purification strategy using a cleavable self-aggregating tag (cSAT) to produce functional wild-type CA protein from E. coli with >95 % purity within a single day. The workflow is compatible with high-throughput formats and scalable from microplates to fermenters, offering significant advantages over conventional purification methods. The purified CA retained full biological activity, as demonstrated by its ability to assemble into higher-order structures in a salt- and protein concentration-dependent manner in vitro. We further evaluated the effects of two well-characterized capsid modulators: CAI, a peptide inhibitor, and lenacapavir (LEN), a clinically approved capsid-targeting drug. Turbidity-based assembly assays confirmed that CAI inhibited and LEN enhanced CA assembly in a dose-dependent manner. When co-administered, CAI and LEN exhibited mutually antagonistic effects. Preincubation with CAI abolished LEN-mediated enhancement, indicating a potential conformational lock imposed by CAI. These findings demonstrate that the column-free strategy enables efficient production of functionally active CA protein suitable for downstream biochemical and inhibitor screening assays. The approach provides a practical tool for accelerating HIV-1 capsid research and antiviral discovery.

To characterize the effects of glaucoma treatment on the corneal endothelium by quantifying corneal endothelial morphology in eyes with and without glaucoma using in vivo specular microscopy.

This is a case-control study of 304 eyes conducted at an ambulatory glaucoma clinic at a tertiary academic institution from August 2021 through July 2023. Primary outcomes include endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (Hex). Images of the central corneal endothelium were obtained using a non-contact Konan NSP-9000 specular microscope (Konan Medical, Irvine, CA, United States). The highest quality image of each cornea was selected for analysis. Each corneal endothelial image was manually graded using the Center Method and analyzed using CellChek (Konan Medical, Irvine, CA, United States) software.

Glaucomatous eyes demonstrate significantly lower corneal ECD compared to control eyes and glaucoma suspect eyes. Topical glaucoma drop use, trabeculectomy, and glaucoma tube shunt surgery independently predict a significant reduction in corneal ECD. Alpha agonist, carbonic anhydrase inhibitor (CAI), and Rho-associated protein kinase (ROCK) inhibitor drops independently predict a significant reduction in corneal ECD, with ROCK inhibitors predicting the greatest absolute decrease.

Eyes treated with topical drops, trabeculectomy, or glaucoma tube shunt implantation demonstrate lower corneal ECD compared to control eyes. Use of topical drops from the alpha agonist, CAI, and ROCK inhibitor classes predicts significant corneal endothelial cell loss.

These findings provide valuable clinical context for the medical management of glaucoma that may reduce adverse outcomes and preserve corneal function in patients receiving ocular hypotensive therapy.

Yang CD, Carbonell BAC, Hussey V, et al. Decoding Corneal Endothelial Loss from Glaucoma Treatment: A Case-Control Stratification Analysis. J Curr Glaucoma Pract 2025;19(2):68-74.