A selective α_vβ₅ integrin antagonist hidden into the anophelin family protein cE5 from the malaria vector Anopheles gambiae

Abstract

A RGD motif was identified in the N‐terminal region of cE5, a potent salivary thrombin inhibitor from the African malaria vector Anopheles gambiae. A peptide (APQ30) encompassing the first 30 amino acids residues of the protein and including the RGD tripeptide was tested in cell adhesion assays and found to inhibit αvβ3 and αvβ5 mediated adhesion. A shorter peptide (APQ16), strongly conserved among members of the A. gambiae species complex and including only the first 16 residues, retained adhesion inhibitory properties, however with enhanced specificity toward αvβ5. In addition, migration and invasion assays showed its capacity to inhibit the invasiveness of the malignant cell lines HepG2 and MDA‐MB231. Altogether our data point to APQ16 as a new promising candidate as theranostic agent.

A Multi-Targeting Approach to Fight SARS-CoV-2 Attachment

“…Therefore, this aspect suggests that a COVID-19 therapy by a multi-targeting approach is the right way and the above reported systems in our opinion could represent sound therapeutic co-receptors to target. Moreover, the demonstrated competitive action of CLQ for the ganglioside site suggests a valid base on the important role that to inhibit the interaction with ganglioside could play in the COVID-19 therapy; such indication prompts us to strongly consider that ligands modulating the interaction with integrins (Del Gatto et al, 2006;Farina et al, 2016;Comegna et al, 2017;Di Gaetano et al, 2018;Fang et al, 2020) or, at the same level, with a sugar through the galectin-domain could represent a suitable therapeutic application. It is important to underline that SARS-CoV-2 S protein-targeting monoclonal antibodies (mAbs) with potent neutralizing activity, a promising therapeutic strategy against COVID-19, target not only the RBD, but also the NTD region (Chi et al, 2020).…”

“…In addition, the tripeptide LDI, homolog to LDV sequence recognized by some integrin sub-families, is also present in the spike glycoproteins of SARS-CoV-2, SARS-CoV, and Bat RaTG137 (Tresoldi et al, 2020). All these indications lead us to think that selective agents able to block integrin binding (Del Gatto et al, 2006;Farina et al, 2016;Comegna et al, 2017;Di Gaetano et al, 2018) could represent a further appealing approach to prevent virus cell attachment and to neutralize the pathogen.…”

Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: A systematic review with multilevel modelling

“…We performed a systematic review with multilevel modelling according to the MOOSE and PRISMA guidelines [16,17] (Reporting Standards Document). Five databases were searched for published studies investigating antibodies to Anopheles salivary antigens as a biomarker for mosquito exposure or malaria transmission published before 30 th of June 2020.…”

Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide

“…The effect of peptides on HepG2 proliferation was analyzed with an RTCA iCELLigence™ instrument (ACEA, San Diego, CA, USA) with a method that uses label-free, real time, non-invasive analysis [ 49 ]. The instrument records a signal of electrical impedance due to the cell covering of gold electrodes located on the surface of a special microplate.…”