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A robust SARS-CoV-2 replication model in primary human epithelial cells at the air liquid interface to assess antiviral agents.
Do, Thuc Nguyen Dan; Donckers, Kim; Vangeel, Laura; Chatterjee, Arnab K; Gallay, Philippe A; Bobardt, Michael D; Bilello, John P; Cihlar, Tomas; De Jonghe, Steven; Neyts, Johan; Jochmans, Dirk.
  • Do TND; KU Leuven - Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
  • Donckers K; KU Leuven - Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
  • Vangeel L; KU Leuven - Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
  • Chatterjee AK; CALIBR - Department of Medicinal Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
  • Gallay PA; CALIBR - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
  • Bobardt MD; CALIBR - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
  • Bilello JP; Gilead Sciences, Inc., Foster City, CA, USA.
  • Cihlar T; Gilead Sciences, Inc., Foster City, CA, USA.
  • De Jonghe S; KU Leuven - Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
  • Neyts J; KU Leuven - Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium. Electronic address: johan.neyts@kuleuven.be.
  • Jochmans D; KU Leuven - Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium. Electronic address: dirk.jochmans@kuleuven.be.
Antiviral Res ; 192: 105122, 2021 08.
Article in English | MEDLINE | ID: covidwho-1283915
Preprint
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ABSTRACT
There are, besides remdesivir, no approved antivirals for the treatment of SARS-CoV-2 infections. To aid in the search for antivirals against this virus, we explored the use of human tracheal airway epithelial cells (HtAEC) and human small airway epithelial cells (HsAEC) grown at the air-liquid interface (ALI). These cultures were infected at the apical side with one of two different SARS-CoV-2 isolates. Each virus was shown to replicate to high titers for extended periods of time (at least 8 days) and, in particular an isolate with the D614G in the spike (S) protein did so more efficiently at 35 °C than 37 °C. The effect of a selected panel of reference drugs that were added to the culture medium at the basolateral side of the system was explored. Remdesivir, GS-441524 (the parent nucleoside of remdesivir), EIDD-1931 (the parent nucleoside of molnupiravir) and IFN (ß1 and λ1) all resulted in dose-dependent inhibition of viral RNA and infectious virus titers collected at the apical side. However, AT-511 (the free base form of AT-527 currently in clinical testing) failed to inhibit viral replication in these in vitro primary cell models. Together, these results provide a reference for further studies aimed at selecting SARS-CoV-2 inhibitors for further preclinical and clinical development.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Antiviral Res Year: 2021 Document Type: Article Affiliation country: J.antiviral.2021.105122

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Antiviral Res Year: 2021 Document Type: Article Affiliation country: J.antiviral.2021.105122