SARS-CoV-2 Fusion Peptide Conjugated to a Tetravalent Dendrimer Selectively Inhibits Viral Infection

Author:

Zannella Carla1ORCID,Chianese Annalisa1ORCID,Monti Alessandra2ORCID,Giugliano Rosa1ORCID,Morone Maria Vittoria1,Secci Francesco3ORCID,Sanna Giuseppina4ORCID,Manzin Aldo4ORCID,De Filippis Anna1ORCID,Doti Nunzianna2ORCID,Galdiero Massimiliano15ORCID

Affiliation:

1. Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy

2. Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy

3. Department of Chemical and Geological Sciences, University of Cagliari, University Campus, 09042 Cagliari, Italy

4. Department of Biomedical Sciences, University of Cagliari, University Campus, 09042 Cagliari, Italy

5. UOC of Virology and Microbiology, University Hospital of Campania “Luigi Vanvitelli”, 80138 Naples, Italy

Abstract

Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein belongs to class I fusion proteins, characterized by a trimer of helical hairpins and an internal fusion peptide (FP), which is exposed once fusion occurs. Many efforts have been directed at finding antivirals capable of interfering with the fusion mechanism, mainly by designing peptides on the two heptad-repeat regions present in class I viral fusion proteins. Here, we aimed to evaluate the anti-SARS-CoV-2 activity of the FP sequence conjugated to a tetravalent dendrimer through a classical organic nucleophilic substitution reaction (SN2) using a synthetic bromoacetylated peptide mimicking the FP and a branched scaffold of poly-L-Lysine functionalized with cysteine residues. We found that the FP peptide conjugated to the dendrimer, unlike the monomeric FP sequence, has virucidal activity by impairing the attachment of SARS-CoV-2 to cells. Furthermore, we found that the peptide dendrimer does not have the same effects on other coronaviruses, demonstrating that it is selective against SARS-CoV-2.

Funder

Campania

Realizzazione di Servizi di Ricerca e Sviluppo per la Lotta contro il COVID-19

Natural and pharmacological inhibition of the early phase of viral replication

Next Generation EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases

Publisher

MDPI AG

Subject

Pharmaceutical Science

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