A Nasal Antiviral Inhibits COVID-19 Transmission in Ferrets

A nasal antiviral created by researchers at Columbia University Vagelos College of Physicians and Surgeons blocked transmission of SARS-CoV-2 in ferrets, suggesting the nasal spray also may prevent infection in people exposed to the new coronavirus, including recent variants. Infection of SARS-CoV-2 requires membrane fusion between the viral envelope and the host cell-mediated by viral spike protein glycoprotein. Upon viral attachment, host factor triggers lead to direct membrane fusion and viral entry. A report states that the development of newly designed lipopeptide fusion inhibitors blocks this important step of infection. Peptides corresponding to the highly conserved Heptad Repeat (HR) domain of C-terminus of S protein may inhibit fusion and prevent infection. Lipid conjugation of HRC-derived inhibitory peptides markedly increases antiviral potency. This strategy has been used for prophylaxis or treatment of parainfluenza type3, Nipah, and measles infection. A study was carried out on ferrets which are an ideal model for assessing the respiratory virus transmission either by direct contact or aerosol transmission. To assess the efficacy of the Dimeric form of SARS CoV-2 S specific lipopeptide preventing the transmission of SARS CoV-2, ferrets were dose prophylactically with the lipopeptide before being co-housed with SARS CoV-2 infected ferrets. The peptide integration into the cell membrane proved key to ensure respiratory tract protection and prevented systemic lipopeptide dissemination.

The lipid conjugated peptides administered intranasally to the animals reached high concentrations both in the upper and lower respiratory tract. Lipid conjugation also enabled activity against viruses. The Dimeric form of SARS CoV-2 S specific lipopeptide is a potent inhibitor of fusion mediated by the SARS CoV-2 S protein, which prevents viral entry when administered intranasally and completely prevents direct contact transmission of SARS CoV-2 in ferrets. A study was also conducted to increase the antiviral potency where a comparison of monomeric and dimeric HRC peptide derivatives was done.

The study confirms that Dimeric cholesterol conjugated peptide was the most potent lipopeptide against SARS CoV-2. This peptide also robustly inhibits fusion mediated by the S protein of several emerging SARS CoV-2 variants. The lipopeptide is the first successful prophylaxis treatment that prevents SARS CoV-2 transmission in relevant animal models providing complete protection during the 24 hour contact period.

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Ref Link: https://science.sciencemag.org/content/early/2021/02/16/science.abf4896

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