Articolo in rivista, 2021, ENG, 10.3390/ijms22126462

More is always better than one: The n-terminal domain of the spike protein as another emerging target for hampering the sars-cov-2 attachment to host cells

Di Gaetano S.; Capasso D.; Delre P.; Pirone L.; Saviano M.; Pedone E.; Mangiatordi G.F.

Institute of Biostructures and Bioimaging, CNR, Naples, 80134, Institute of Biostructures and Bioimaging, CNR, 80134, Naples, Italy;, , Italy; CIRPEB, University of Naples "Federico II", Naples, 80134, CIRPEB, University of Naples "Federico II", 80134, Naples, Italy;, , Italy; CESTEV, University of Naples "Federico II", Naples, 80145, CESTEV, University of Naples "Federico II", 80145, Naples, Italy, , Italy; Institute of Crystallography, CNR, Bari, 70126, Institute of Crystallography, CNR, 70126, Bari, Italy;, , Italy; Chemistry Department, University of Bari, Bari, 70121, Chemistry Department, University of Bari, 70121, Bari, Italy, , Italy

Although the approved vaccines are proving to be of utmost importance in containing the Coronavirus disease 2019 (COVID-19) threat, they will hardly be resolutive as new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, a single-stranded RNA virus) variants might be insensitive to the immune response they induce. In this scenario, developing an effective therapy is still a dire need. Different targets for therapeutic antibodies and diagnostics have been identified, among which the SARS-CoV-2 spike (S) glycoprotein, particularly its receptor-binding domain, has been defined as crucial. In this context, we aim to focus attention also on the role played by the S N-terminal domain (S1-NTD) in the virus attachment, already recognized as a valuable target for neutralizing antibodies, in particular, building on a cavity mapping indicating the presence of two druggable pockets and on the recent literature hypothesizing the presence of a ganglioside-binding domain. In this perspective, we aim at proposing S1-NTD as a putative target for designing small molecules hopefully able to hamper the SARS-CoV-2 attachment to host cells.

International journal of molecular sciences (Print) 22

Keywords

SARS-Cov-2, spike protein

CNR authors

Delre Pietro, Di Gaetano Sonia, Pedone Emilia Maria, Mangiatordi Giuseppe Felice, Pirone Luciano, Saviano Michele

CNR institutes

IBB – Istituto di biostrutture e bioimmagini, IC – Istituto di cristallografia