Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters.

Cricetinae Animals SARS-CoV-2 Mesocricetus COVID-19 / prevention & control Lung Nucleotidyltransferases RNA, Viral Antiviral Agents / pharmacology
SARS-CoV-2 chemoprophylaxis favipiravir pibrentasvir remdesivir

Journal

Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722

Informations de publication

Date de publication:
27 Oct 2023
Historique:
received: 13 10 2023
revised: 23 10 2023
accepted: 24 10 2023
medline: 27 11 2023
pubmed: 25 11 2023
entrez: 25 11 2023
Statut: epublish

Résumé

Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed.

Identifiants

DOI: 10.3390/v15112161 PMID: 38005839 PMC: PMC10675045
pubmed: 38005839
pii: v15112161
doi: 10.3390/v15112161
pmc: PMC10675045
pii:
doi:

Substances chimiques

Nucleotidyltransferases EC 2.7.7.-
RNA, Viral 0
Antiviral Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI134091
Pays : United States
Organisme : NIAID NIH HHS
ID : R24 AI118397
Pays : United States
Organisme : NIH HHS
ID : R24AI118397
Pays : United States
Organisme : Swiss National Science Foundation
ID : IZSEZ0_213289
Pays : Switzerland
Organisme : NIH HHS
ID : R01AI134091
Pays : United States

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Auteurs

Eduardo Gallardo-Toledo (E)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0009-0000-8534-9030

Megan Neary (M)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0002-4960-2139

Joanne Sharp (J)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0001-8482-5736

Joanne Herriott (J)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.

Edyta Kijak (E)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.

Chloe Bramwell (C)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0001-8274-457X

Paul Curley (P)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.

Usman Arshad (U)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0003-1586-1885

Henry Pertinez (H)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.

Rajith K R Rajoli (RKR)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0002-6015-5712

Anthony Valentijn (A)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.

Helen Cox (H)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.

Lee Tatham (L)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0001-9448-8876

Anja Kipar (A)

Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UK.
Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
ORCID: 0000-0001-7289-3459

James P Stewart (JP)

Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0002-8928-2037

Andrew Owen (A)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L69 3BX, UK.
ORCID: 0000-0002-9819-7651

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Arvicolinae › Cricetinae › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Eucaryotes › Animaux › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Arvicolinae › Cricetinae › Mesocricetus › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Appareil respiratoire › Poumon › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN viral › Chemoprophylactic Assessment of Combined...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Chemoprophylactic Assessment of Combined...