tetano
Editor, Senior Moderator
Viruses
. 2021 Aug 23;13(8):1667.
doi: 10.3390/v13081667.
Peptide Platform as a Powerful Tool in the Fight against COVID-19
Michela Murdocca[SUP] 1 [/SUP], Gennaro Citro[SUP] 1 [/SUP], Isabella Romeo[SUP] 2 3 [/SUP], Antonio Lupia[SUP] 3 [/SUP], Shane Miersch[SUP] 4 5 [/SUP], Bruno Amadio[SUP] 6 [/SUP], Alessia Bonomo[SUP] 1 [/SUP], Antonio Rossi[SUP] 7 [/SUP], Sachdev S Sidhu[SUP] 4 5 [/SUP], Pier Paolo Pandolfi[SUP] 8 [/SUP], Stefano Alcaro[SUP] 2 3 [/SUP], Federica Carla Sangiuolo[SUP] 1 [/SUP], Giuseppe Novelli[SUP] 1 9 10 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; SARS-CoV-2 variants; VSVpp.SARS-2S; conserved RBD region; drug design; peptides; protein–protein docking.
. 2021 Aug 23;13(8):1667.
doi: 10.3390/v13081667.
Peptide Platform as a Powerful Tool in the Fight against COVID-19
Michela Murdocca[SUP] 1 [/SUP], Gennaro Citro[SUP] 1 [/SUP], Isabella Romeo[SUP] 2 3 [/SUP], Antonio Lupia[SUP] 3 [/SUP], Shane Miersch[SUP] 4 5 [/SUP], Bruno Amadio[SUP] 6 [/SUP], Alessia Bonomo[SUP] 1 [/SUP], Antonio Rossi[SUP] 7 [/SUP], Sachdev S Sidhu[SUP] 4 5 [/SUP], Pier Paolo Pandolfi[SUP] 8 [/SUP], Stefano Alcaro[SUP] 2 3 [/SUP], Federica Carla Sangiuolo[SUP] 1 [/SUP], Giuseppe Novelli[SUP] 1 9 10 [/SUP]
Affiliations
- PMID: 34452531
- DOI: 10.3390/v13081667
Abstract
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.
Keywords: COVID-19; SARS-CoV-2 variants; VSVpp.SARS-2S; conserved RBD region; drug design; peptides; protein–protein docking.