The outbreak of SARS-CoV-2 infections around the world has prompted scientists to explore different approaches to develop therapeutics against COVID-19. This study focused on investigating the mechanism of inhibition of clioquinol (CLQ) and its derivatives (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ), 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) against the viral glycoprotein, and human angiotensin-converting enzyme-2 (hACE-2) involved in SARS-CoV-2 entry. The drugs were docked at the exopeptidase site of hACE-2 and receptor binding domain (RBD) sites of SARS-CoV-2 S-gp to calculate the binding affinity of the drugs. To understand and establish the inhibitory characteristics of the drugs, molecular dynamic (MD) simulation of the best fit docking complex performed. Evaluation of the binding energies of the drugs to hACE-2 after 100 ns MD simulations revealed CLQ to have the highest binding energy value of -40.4 kcal/mol close to MLN-7640 (-45.4 kcal/mol), and higher than the exhibited values for its derivatives: CLBQ (-34.5 kcal/mol) and CLCQ (-24.8 kcal/mol). This suggests that CLQ and CLBQ bind more strongly at the exopeptidase site than CLCQ. Nevertheless, the evaluation of binding affinity of the drugs to SARS-CoV-2 S-gp showed the drugs are weakly bound at the RBD site, with CLBQ, CLCQ, CLQ exhibiting relatively low energy values of -16.8 kcal/mol, -16.34 kcal/mol, -12.5 kcal/mol, respectively compared to the reference drug, Bisoxatin (BSX), with a value of -25.8 kcal/mol. The structural analysis further suggests decrease in systems stability and explain the mechanism of inhibition of clioquinol against SARS-CoV-2 as reported in previous in vitro study. Communicated by Ramaswamy H. Sarma

Maternal mortality and morbidity are critical health challenges in the U.S., and building the perinatal workforce is a key to providing high-quality maternal medical care and services. Texas Southern University (TSU), home to a Doctor of Pharmacy program, launched the first Maternal Health Education and Research Training (MHERT) program to educate a cohort of high school, pharmacy, and health sciences students. Aiming to raise awareness of maternal health issues, build research skills, and promote action-based solutions. MHERT integrated online self-paced interactive lessons with hands-on research or community projects. Topics included maternal health epidemiology, causes of morbidity and mortality, research methods, literature reviews, and the development of action plans addressing maternal health challenges. Assessment tools included quizzes, open-ended reflection responses, training surveys, and course evaluations. Running from 3 June to 26 July 2024, the program enrolled 22 students. All participants completed both course components. Course evaluations showed strong and consistent satisfaction with the program, with teaching effectiveness rated at 95% and 96% for mid-program and final evaluations, respectively. MHERT enhanced participants’ understanding of maternal health, improved research skills, and encouraged community engagement and interdisciplinary collaboration. It offers a scalable model to strengthen public health education among high school, pharmacy, and health sciences students.

Viruses undergo mutations over time, most of which have little to no impact. However, certain changes can significantly influence viral traits such as transmissibility and disease severity. Newer SARS-CoV-2 variants, including XBB.1.5, XBB.1.16, EG.5, and BA.2.86, have emerged with key mutations—D405N, G446S, N460K, and R408S—altering their biological behavior. This study explores how mutations in the receptor-binding domain (RBD) of various SARS-CoV-2 variants affect their molecular interactions, structural stability, and binding affinity with the human ACE-2 receptor (hACE-2), offering insights valuable for drug discovery. Using computational methods, binding free energy calculations revealed that variants such as BQ.1.1, CH.1.1, EG.5, EG.5.1, XBB.1, XBB.1.5, XBB.1.9.1, XBB.2.3, and BA.2.75 demonstrate stronger binding to hACE-2 than the wild-type (WT), which exhibited a binding energy of −35.24 ± 8.97 kcal/mol. This enhanced binding is linked to increased hydrogen bonds (H-bonds) and electrostatic interactions, with correlation coefficients of 0.51 and 0.28, respectively. Structural stability analyses, based on average RMSD values, showed that most mutations did not compromise the RBD-hACE-2 complex’s integrity, except in variants XBB.1.5, XBB.1.9.1, and XBB.1.9.2. These findings suggest that specific mutations enhance interactions through H-bonds, hydrophobic effects, and electrostatic forces, contributing to overall stability. In summary, this study highlights that several SARS-CoV-2 variants bind more effectively to hACE-2 than the WT and earlier variants like BA.5 and BQ.1. These stronger interactions may underlie their higher transmission rates. The molecular insights provided here improve understanding of how specific mutations influence the virus’s behavior, aiding future therapeutic development.

Despite the recent progress in the diagnosis of tuberculosis (TB), the chemotherapeutic management of TB continues to be challenging. Mycobacterium tuberculosis (Mtb), the etiological agent of TB, is classified as the 13th leading cause of death globally. In addition, 450,000 people were reported to develop multi-drug-resistant TB globally. The current project focuses on targeting methionine aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the excision of the N-terminal methionine (NME) during protein synthesis, allowing the enzyme to be an auspicious target for the development of novel therapeutic agents for the treatment of TB. Mtb possesses two MetAP1 isoforms, MtMetAP1a and MtMetAP1c, which are vital for Mtb viability and, hence, a promising chemotherapeutic target for Mtb therapy. In this study, we cloned and overexpressed recombinant MtMetAP1c. We investigated the in vitro inhibitory effect of the novel MetAP inhibitor, OJT008, on the cobalt ion- and nickel ion-activated MtMetAP1c, and the mechanism of action was elucidated through an in silico approach. The compound’s potency against replicating and multi-drug-resistant (MDR) Mtb strains was also investigated. The induction of the overexpressed recombinant MtMetAP1c was optimized at 8 h with a final concentration of 1 mM Isopropyl β-D-1-thiogalactopyranoside. The average yield from 1 L of Escherichia coli culture for MtMetAP1c was 4.65 mg. A preliminary MtMetAP1c metal dependency screen showed optimum activation with nickel and cobalt ions occurred at 100 µM. The half-maximal inhibitory concentration (IC₅₀) values of OJT008 against MtMetAP1c activated with CoCl₂ and NiCl₂ were 11 µM and 40 µM, respectively. The in silico study showed OJT008 strongly binds to both metal-activated MtMetAP1c, as evidenced by strong molecular interactions and a higher binding score, thereby corroborating our result. This in silico study validated the pharmacophore’s metal specificity. The potency of OJT008 against both active and MDR Mtb was <0.063 µg/mL. Our study reports OJT008 as an inhibitor of MtMetAP1c, which is potent at low micromolar concentrations against both active susceptible and MDR Mtb. These results suggest OJT008 is a potential lead compound for the development of novel small molecules for the therapeutic management of TB.

Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal and perinatal morbidity in the United States. Despite advances in care, recent