Biology subjects

Ramos, Y.

Publications and source records attributed to Ramos, Y..

3 recordsLinked to original sources

bioRxiv2021

SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to use neutralizing antibodies to block viral sites binding to the hosts cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of the immunization and correlates well with viral neutralization. Here we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid induce a potent immune response in laboratory animals. Some advantages of the immunization with the viral antigen coupled to tetanus toxoid have become evident such as predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. This paper demonstrates that subunit conjugate vaccines can be an alternative for COVID-19, paving the way for other viral conjugate vaccines based on the use of small viral proteins involved in the infection process.

immunology↗

bioRxiv2021

Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.

cancer biology↗

bioRxiv2020

The low-density lipoprotein receptor-related protein-1 is essential for Dengue virus infection

Dengue virus (DENV) causes the most prevalent and rapidly spreading arboviral disease of humans. It enters human cells by receptor-mediated endocytosis. Numerous cell surface proteins have been proposed as DENV entry factors. Among these, the phosphatidylserine receptor TIM-1 is the only one known to mediate virus internalization. However, several cellular models lacking TIM-1 are permissive to DENV infection, suggesting that other receptors exist. Here we show that the Low-density lipoprotein receptor-related protein-1 (LRP1) binds DENV virions by interacting with the DIII of the viral envelope glycoprotein. DENV infection is effectively inhibited by the purified receptor at 5x10-8 mol/L and the interaction of the envelope protein with LRP1 is also blocked by a natural ligand of LRP1. Depletion of LRP1 causes 100-fold lower production of infectious virus than controls. Our results indicate that LRP1 is another DENV receptor thus, becoming an attractive target to evaluate for the development of effective antiviral drugs against DENV. Author summaryDengue virus (DENV) is a complex of four related viruses, recognized as serotypes, designated as DENV1-4. Any of the four DENV serotypes can cause a self-limited disease of mild flu-like symptoms known as dengue or its life threatening form, severe dengue, with hemorrhagic manifestations, organ impairment and shock. This disease is widely spread in tropical and sub-tropical areas worldwide, where the incidence of severe dengue has been increasing steadily. So far, efforts that target components of the viral replication machinery in order to develop a specific antiviral drug for dengue disease patients have failed. Thus, identifying the cell surface receptors used by DENV to enter host cells would provide a new molecular target to develop inhibitory drugs. Here, we evaluate the Low density lipoprotein receptor-related protein-1 (LRP1) as a putative DENV receptor. We present evidence demonstrating that LRP1 binds DENV through the viral envelope protein. We show that the production of infective virus is impaired on cells lacking LRP1, and that purified LRP1 is a potent blocker of DENV infection. These results are consistent with LRP1 playing an important role on DENV entry, making this receptor a molecule of interest on the investigation for medical treatments of dengue/severe dengue disease.

biochemistry↗