SARS-CoV-2-Mediated Lung Edema and Replication Are Diminished by Cystic Fibrosis Transmembrane Conductance Regulator Modulators

• DOI: 10.1128/mbio.03136-22
• Publication Date: 2023-01-10T14:06:10Z
• Authors: Jose M. Honrubia; Javier Gutierrez-...; Alejandro Sanz-Bravo; Ezequiel González...; Diego Muñoz-Santos; Carlos Castaño-Ro...; Li Wang; Marta Villarejo-T...; Jorge Ripoll-Gómez; Ana Esteban; Raul Fernandez-De...; Pedro José Sánche...; Juan Carlos Oliveros; Stanley Perlman; Paul B. McCray; Isabel Sola; Luis Enjuanes
• Keywords: Replication

Coronaviruses (CoVs) of genera α, β, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting the last four residues envelope (E) protein (PBM core). PBMs may bind over 400 cellular containing PDZ domains (an acronym formed by combination first letter names three where this domain was identified), making them relevant for control cell function. Three highly pathogenic human CoVs been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) Middle East (MERS-CoV), SARS-CoV-2. The were virulence factors. SARS-CoV mutants in which E PBM core replaced from virulent or attenuated constructed. These showed gradient virulence, depending on whether alternative introduced derived an CoV. Gene expression patterns lungs mice infected with SARS-CoVs encoding each different analyzed RNA sequencing lung tissues. SARS-CoV-2 dysregulated gene related ion transport homeostasis. Decreased cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential alveolar edema resolution, shown. Reduced CFTR mRNA levels associated accumulation alveoli Compounds increased activity, significantly reduced growth cultured cells protected against mouse infection, suggesting is mediated decreased expression.