Small molecules that treat or prevent viral infections
Inventors
Bradley K McConnell, Arfaxad Reyes Alcaraz, John W Craft, Robert J Schwartz
Publication date 2026/3/10
Patent office US
Patent number 12569467
Application number 18111210

Description
The invention relates to anti-viral compounds suitable for use in blocking virus entry into cells, and methods of blocking virus entry into cells by associating the cells with the anti-viral compounds. The associating may occur in vitro, or in vivo in a subject through administration of the anti-viral compounds to the subject. The invention also relates to methods of treating or preventing a viral infection in a subject by administering to the subject at least one anti-viral compound. The subject may be a human being suffering from or vulnerable to the viral infection. The virus may include a coronavirus, such as severe acute respiratory syndrome-related coronavirus 2 (SARS-COV-2).

Scholar articles Small molecules that treat or prevent viral infections
BK McConnell, AR Alcaraz, JW Craft, RJ Schwartz - US Patent 12,569,467, 2026

The inability of CD8+ effector T cells (Teffs) to reach tumor cells is an important aspect of tumor resistance to cancer immunotherapy. The recruitment of these cells to the tumor microenvironment (TME) is regulated by integrins, a family of adhesion molecules that are expressed on T cells. Here, we show that 7HP349, a small-molecule activator of lymphocyte function–associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated the preferential localization of tumor-specific T cells to the tumor and improved antitumor response. 7HP349 monotherapy had modest effects on anti–programmed death 1–resistant (anti–PD-1–resistant) tumors, whereas combinatorial treatment with anti–cytotoxic T lymphocyte–associated protein 4 (anti–CTLA-4) increased CD8+ Teff intratumoral sequestration and synergized in cooperation with neutrophils in inducing cancer regression. 7HP349 intratumoral CD8+ Teff enrichment activity depended on CXCL12. We analyzed gene expression profiles using RNA from baseline and on treatment tumor samples of 14 melanoma patients. We identified baseline CXCL12 gene expression as possibly improving the likelihood or response to anti–CTLA-4 therapies. Our results provide a proof-of-principle demonstration that LFA-1 activation could convert a T cell–exclusionary TME to a T cell–enriched TME through mechanisms involving cooperation with innate immune cells.

LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade

Our new paper talks about Spleen Tyrosine Kinase and signaling through interactions with integrins: PUB MED LINK and is titled Identification of Inhibitors of Integrin Cytoplasmic Domain Interactions With Syk. This was collaboration between the University of Houston and the Texas Heart Institute.

We recently discussed our drug discoveries at theHewlett Packarad Enterprise Data Science Institute

Checkout our new paper: Magnetic Resonance Imaging of Atherosclerotic Plaque at Clinically Relevant Field Strengths (1T) by Targeting the Integrin α4β1.PUBMED
https://www.ncbi.nlm.nih.gov/pubmed/29487319
Texas Heart Institute has developed a new technology that allows a cargo in a liposome to be selectively delivered to tissues expressing α4β1. This is important because plaques express this integrin and we are working on derivatives of this concept for other cargos and other integrins. Imagine therapeutics loaded in the liposome and brought at higher local concentration selectively to the plaques.

I am working on a number of docking projects. The exciting part is that I have a number of new students that are interested in working on the both the computational and wet lab validation of our predictions. We are refining the docking systems these will do NMR next week.

With the extra time on the last day we took the Munich -> Paris express train to Strasburg. The city was spectacular, with amazing little narrow streets and unique postcard shops.

I attended the “Simulating Soft and Active Matter with ESPResSo, ESPResSo++, and VOTCA” conference/workshop/developers meeting at the Institute for Computational Physics of the University of Stuttgart, Germany. Compiled supporting software libraries for both laptop and UH computation cluster. Those included: Boost, Cython, FFTW3, GSL, GROMAC, VOTCA, ESPRESSO, and ESPRESSO++. I also presented a poster developing: “Phosphorylation Mimicry in Espresso; Charge Gradients and Dynamics” at the conference.

This week has been a greatly enriching and learning experience at the 49th US-Japan Conference on Cholera. This conference integrates both basic science and field work, bringing a broad range of communities together to impact world health. I was deeply inspired by the stories from the teams coming back from Africa. Their commitment to interdict during a cholera outbreak is unwavering despite the logistic and security challenges in the field. Also a significant number of developments in vaccines and how they can be cost effectively targeted to vulnerable populations was encouraging. Each evening after the conference we were able to continue the networking over great central Florida fare, such as these at the Harries Seafood in downtown Gainsville.

We are investigation the underlying mechanisms that cause Cholera to be significantly more deadly as compared to Enterotoxin despite the high level of commonality between the structures. A few amino acids variations in the A2 tail region leads to differential effects including the strength of domain-domain interactions and water access through a small gap in the A-domain to B-domain interface.