Biology subjects

Taha, Z.

Publications and source records attributed to Taha, Z..

3 recordsLinked to original sources

bioRxiv2026

Ex vivo maturation of the malaria parasite egress protease SERA6 aids pathway dissection and inhibitor development.

Release (egress) of malaria parasites from host red blood cells (RBC) is a protease-dependent process involving breakdown of the RBC cytoskeleton by a parasite cysteine protease-like protein called SERA6. In the penultimate step of the egress cascade, SERA6 undergoes autoproteolytic maturation triggered upon cleavage by a serine protease called SUB1 and requiring interactions between SERA6 and fragments of another parasite protein called MSA180. Egress can be blocked by treatment of intraerythrocytic parasites with small molecules that prevent the autocatalytic SERA6 maturation step, suggesting that SERA6 is a druggable target. Here we describe the development of a cell-free in vitro system that recapitulates SERA6 maturation. We use the assay to confirm the strict requirement for MSA180 in SERA6 maturation by SUB1 and to show that these 3 components are sufficient for SERA6 maturation. Using a synthetic peptide substrate based on a predicted autocatalytic cleavage site we demonstrate that the fully mature SERA6 is an active proteolytic enzyme and we validate improved small molecule inhibitors of SERA6. Our lead inhibitory compound efficiently blocks egress of asexual blood stage parasites, confirming SERA6 as a new potential antimalarial drug target.

biochemistry↗

bioRxiv2021

A small molecule drug screening identifies colistin sulfate as an enhancer of Natural Killer cell cytotoxicity.

Because of their crucial role in tumor immunity, NK cells have quickly become a prime target for immunotherapies, with adoptive transfer of NK cells and the use of NK cell engagers quickly moving to clinical stage. On the other hand, only few studies have focused on small molecule drugs capable of unleashing NK cell against cancer. In this context, repurposing small molecule is an attractive strategy to identify new immunotherapies from already approved drugs. Here, we screened 1,200 FDA-approved drugs from the Prestwick Chemical Library, to identify compounds that increase NK cell cytotoxic potential. Using a high-throughput luciferase-release cytotoxicity assay, we found that the antibiotic colistin sulfate increased cytotoxicity of human NK cells towards cancer cells. The effect of colistin was short lived and was not observed when NK cells were pretreated with the drug, showing how NK cell activity was potentiated only when the compound was present at the time of recognition of cancer cells. Further studies are needed to uncover the mechanism of action and the pre-clinical efficacy of colistin sulfate in mouse cancer models.

immunology↗

bioRxiv2021

Characterization of Critical Determinants of ACE2-RBD Interaction

Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. Utilizing our recently developed NanoBiT technology-based biosensor, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, before and after the addition of competitive inhibitors, as well as neutralizing antibody activity. These critical determinants of virus-host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.

microbiology↗