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1.
Chem Commun (Camb) ; 58(85): 11913-11916, 2022 Oct 25.
Article in English | MEDLINE | ID: covidwho-2050566

ABSTRACT

The single-stranded RNA genome of SARS-CoV-2 contains some G-quadruplex-forming G-rich elements which are putative drug targets. Here, we performed a ligand-based pharmacophore virtual screening of FDA approved drugs to find candidates targeting such RNA structures. Further in silico and in vitro assays identified three drugs as emerging SARS-CoV-2 RNA G-quadruplex binders.


Subject(s)
COVID-19 , Drug Repositioning , Humans , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , COVID-19/drug therapy , Ligands , Molecular Docking Simulation , RNA, Viral/genetics , SARS-CoV-2 , G-Quadruplexes
3.
Mol Ther ; 30(5): 1979-1993, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1677227

ABSTRACT

As of December 2021, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single-chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the Delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Because of their high efficiency, remarkable stability, resilience to nebulization, and low cost of production, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Humans , Immunoglobulin Fragments , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus
4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295491

ABSTRACT

As of October 2021, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Due to high efficiency, remarkable stability, resilience to nebulization and low production cost, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.

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