Peptide Platform as a Powerful Tool in the Fight against COVID-19

Viruses

Giuseppe Novelli¹  Gennaro Citro¹  Federica Carla Sangiuolo¹  Michela Murdocca¹  Alessia Bonomo¹  Stefano Alcaro²  Isabella Romeo²  Antonio Rossi³  Antonio Lupia⁴  Pier Paolo Pandolfi⁵  Bruno Amadio⁶  Sachdev S. Sidhu⁷  Shane Miersch⁷ 

[1] Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy;Department of Health Science, University ‘Magna Graecia’ of Catanzaro, Campus “S. Venuta”, Viale Europa, 88100 Catanzaro, Italy;Institute of Translational Pharmacology, CNR, 00133 Rome, Italy;Net4Science Academic Spin-Off, University ‘Magna Graecia’ of Catanzaro, Campus “S. Venuta”, Viale Europa, 88100 Catanzaro, Italy;Renown Institute for Cancer, Nevada System of Higher Education, Reno, NV 89502, USA;SAFU-IRE, Regina Elena Cancer Institute, 00128 Rome, Italy;The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada;

关键词: COVID-19;    peptides;    protein–protein docking;    conserved RBD region;    SARS-CoV-2 variants;    VSVpp.SARS-2S;   

DOI  :  10.3390/v13081667

来源: DOAJ

【 摘 要 】

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic causing over 195 million infections and more than 4 million fatalities as of July 2021.To date, it has been demonstrated that a number of mutations in the spike glycoprotein (S protein) of SARS-CoV-2 variants of concern abrogate or reduce the neutralization potency of several therapeutic antibodies and vaccine-elicited antibodies. Therefore, the development of additional vaccine platforms with improved supply and logistic profile remains a pressing need. In this work, we have validated the applicability of a peptide-based strategy focused on a preventive as well as a therapeutic purpose. On the basis of the involvement of the dipeptidyl peptidase 4 (DPP4), in addition to the angiotensin converting enzyme 2 (ACE2) receptor in the mechanism of virus entry, we analyzed peptides bearing DPP4 sequences by protein–protein docking and assessed their ability to block pseudovirus infection in vitro. In parallel, we have selected and synthetized peptide sequences located within the highly conserved receptor-binding domain (RBD) of the S protein, and we found that RBD-based vaccines could better promote elicitation of high titers of neutralizing antibodies specific against the regions of interest, as confirmed by immunoinformatic methodologies and in vivo studies. These findings unveil a key antigenic site targeted by broadly neutralizing antibodies and pave the way to the design of pan-coronavirus vaccines.

【 授权许可】

Unknown