Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2

Membranes

Maria C. Henao¹  Luis H. Reyes¹  Camila Ocasion¹  Juan C. Cruz²  Cristina González-Melo²  Javier Cifuentes²  Valentina Quezada²  Paola Ruiz Puentes²  Juan C. Burgos³  Arnovis Yepes⁴ 

[1] Grupo de Diseño de Productos y Procesos (GDPP), Department of Chemical and Food Engineering, Universidad de los Andes, Bogota, DC 111711, Colombia;Grupo de Investigación en Nanobiomateriales, Ingeniería Celular y Bioimpresión (GINIB), Department of Biomedical Engineering, Universidad de los Andes, Bogota, DC 111711, Colombia;Grupo de Modelado Computacional (GruMoC), Chemical Engineering Program, Universidad de Cartagena, Cartagena 130015, Colombia;Physical Sciences Program, Universidad de Cartagena, Cartagena 130015, Colombia;

关键词: spike glycoprotein;    SARS-CoV-2;    molecular dynamics;    cell-penetrating peptides;    drug delivery;    biocompatibility;   

DOI  :  10.3390/membranes12060600

来源: DOAJ

【 摘 要 】

At the beginning of 2020, the pandemic caused by the SARS-CoV-2 virus led to the fast sequencing of its genome to facilitate molecular engineering strategies to control the pathogen’s spread. The spike (S) glycoprotein has been identified as the leading therapeutic agent due to its role in localizing the ACE2 receptor in the host’s pulmonary cell membrane, binding, and eventually infecting the cells. Due to the difficulty of delivering bioactive molecules to the intracellular space, we hypothesized that the S protein could serve as a source of membrane translocating peptides. AHB-1, AHB-2, and AHB-3 peptides were identified and analyzed on a membrane model of DPPC (dipalmitoylphosphatidylcholine) using molecular dynamics (MD) simulations. An umbrella sampling approach was used to quantify the energy barrier necessary to cross the boundary (13.2 to 34.9 kcal/mol), and a flat-bottom pulling helped to gain a deeper understanding of the membrane’s permeation dynamics. Our studies revealed that the novel peptide AHB-1 exhibited comparable penetration potential of already known potent cell-penetrating peptides (CPPs) such as TP2, Buforin II, and Frenatin 2.3s. Results were confirmed by in vitro analysis of the peptides conjugated to chitosan nanoparticles, demonstrating its ability to reach the cytosol and escape endosomes, while maintaining high biocompatibility levels according to standardized assays.

【 授权许可】

Unknown