Izhaki-Tavor, L. S. | bioRxiv Science

bioRxiv2025

Ribosomal Architecture and rRNA Modification Landscape in the Tick-Borne Parasite Babesia divergens

Babesia is a tick-borne intracellular apicomplexan parasite responsible for diseases ranging from mild to fatal, with a broadening geographic distribution. Due to the complex life cycle of Babesia species, their survival depends on the precise control of gene expression, which is primarily regulated by epigenetic, transcriptional, and post-transcriptional mechanisms. High-resolution structural information on key components of the translation machinery, such as ribosomes, could aid in the development of antiparasitic drugs. Here, we report cryo-EM ribosome structures (2.6 [A]) from the tick-borne apicomplexan pathogen Babesia divergens, showing associated tRNAs, an mRNA fragment, and RACK1, a signaling scaffold crucial to translation regulation. Density map analysis displays ribosome regions at atomic resolution (1.7 [A]), which, when combined with nanopore sequencing, enabled the comprehensive identification of rRNA modifications, including modifications unreported in other organisms. The new rRNA modifications localize not only to the reduced Babesia rRNA expansion segments but also to functionally essential ribosomal sites, uncovering new avenues for therapeutic intervention against babesiosis.

microbiology↗

bioRxiv2025

Monoclonal Antibodies from COVID-19 Convalescent Patients Target Cryptic Epitopes for Universal SARS-CoV-2 Neutralization

The COVID-19 pandemic, which has resulted in over seven million global fatalities, poses a substantial threat to public health and precipitated a global economic crisis. Emerging variants of concern (VOCs) with enhanced transmissibility and improved immune evasion may compromise the efficacy of current antiviral and immunotherapies, necessitating comprehensive investigations into the immune response to SARS-CoV-2. The conformational dynamics of the receptor binding domain (RBD) in SARS-CoV-2 spike and the presentation of neutralizing antibody epitopes influence viral transmission and infection rates. In this study, we have identified highly conserved non-RBM epitopes for two potent monoclonal antibodies (mAbs), TAU-1109 and TAU-2310, isolated from convalescent human patients, which contribute to the broad neutralizing activity of these mAbs against all the circulating VOCs, including the recently emerged Omicron subvariants. We employed high- resolution structural data in conjunction with systematic biochemical investigation to elucidate the neutralization mechanism of TAU-1109 and TAU-2310. The mechanism involves antibody-mediated destabilization of the spike trimer, resulting in the premature shedding of the S1 subunit and rendering the spike incapable of mediating host cell entry. The identification of conserved cryptic epitopes in our study advances the mechanistic understanding of immune response against SARS-CoV-2, providing novel avenues for the development of universal therapeutic antibodies and vaccines to combat COVID-19.

biochemistry↗