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Can a lipopeptide based nasal spray prevent COVID-19?

In ferrets, a nasal spray prevents COVID-19 infection. Can a similar nasal spray for humans do the same? It appears that this is the case. In comparison to monoclonal antibodies lipopeptide or lipoprotein based nasal sprays for the prevention of viral infections are less expensive to produce.

Several recent studies indicate that inhibitory peptides blocking the membrane fusion step between the SARS-CoV-2 viral spike protein and the host membranes prevent the entry of coronavirus SARS-CoV-2 into host cells. Nasal sprays containing a lipid form of blocking peptides are thought to prevent transmission of the viral particle to the host and thereby preventing infection by SARS-CoV-2 preventing COVID-19.

Vries et al. recently reported that in ferrets, a dimeric form of a SARS-CoV-2-derived lipopeptide acts as a potent fusion and infection inhibitor in vitro and inhibits the transmission of the virus in vivo. Spraying an inhibitory lipopeptide daily into the noses of ferrets completely prevented the SARS-CoV-2 direct-contact transmission during a period of 24-hours that were in close contact with infected animals. The S protein allows the coronavirus to bind to the host cell receptor ACE2. Peptides designed to interfere with the binding event can inhibit viral entry, thereby preventing infection. Inhibiting peptides are also known as antiviral-peptides. Antiviral peptides interfere with the binding of the SARS coronavirus spike RBD to the cellular receptor, ACE2. These peptides are also known as "Coronavirus Inhibitory Peptides." Biological active lipopeptides consist of lipid groups connected to peptide moities.

The reported in vitro and in vivo results indicate that prophylactic intranasal administration of the [SARS-HRC-PEG4]2-chol or SARS-HRC-PEG4-chol peptide will prevent virus transmission from infected to uninfected individuals for a period of 24-hour period of intense direct contact. The reported in vitro data suggest that this lipopeptide is also effective against emerging variants with mutations in the spike protein and possibly against other coronaviruses.

The lipopeptides used consisted of a peptide sequence corresponding to the highly conserved heptad repeat (HR) domain at the C-terminus of the S protein, a spacer sequence, a polyethylene oxide (PEG) spacer attached to cholesterol.

Lipopeptides used for the study

  Ac-DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-GSGSGC-PEG4-Cholesterol

[Ac-DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-GSGSGC-PEG4]2-Cholesterol


Schematic of the coronavirus spike (S) protein domain structure

The location of receptor-binding subunit S1, the membrane-fusion subunit S2, the transmembrane anchor (TM), the intercellular tail (IC) are indicated. The location of the S1 N-terminal domain (S1-NTD), the S1 C-terminal domain (S1-CTD), the fusion peptide (FP), and the heptade repeat regions N and C (HR-N and HR-C) are indicated as well.

The following image shows the annotated sequence for SARS-CoV-2 spike proteins from the coronavirus associated with COVID-19 originating in Wuhan of Hubei province in China.




Bio-Synthesis does not provide the peptide spray.

However, Bio-Synthesis offers a full spectrum of high-quality custom peptide and modification services by direct solid-phase chemical synthesis.

Reference

Rory D. de Vries, Katharina S. Schmitz, Francesca T. Bovier, Danny Noack, Bart L. Haagmans, Sudipta Biswas, Barry Rockx, Samuel H. Gellman, Christopher A. Alabi, Rik L. de Swart, Anne Moscona, Matteo Porotto; Intranasal fusion inhibitory lipopeptide prevents direct contact SARS-CoV-2 transmission in ferrets. bioRxiv 2020.11.04.361154.

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