Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283806747> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W4283806747 abstract "Abstract Protease inhibitors are among the most powerful antiviral drugs. A first protease inhibitor against the SARS-CoV-2 protease 3CLpro, Paxlovid (nirmatrelvir / ritonavir), has recently been authorized by the U.S. FDA for emergency use (EUA 105 Pfizer Paxlovid). To find resistant mutants against the protease-inhibitor-component of Paxlovid, nirmatrelvir, we engineered a chimeric Vesicular Stomatitis Virus (VSV). By replacing an intergenic region, which is essential for separate gene transcription, with 3CLpro, this chimeric VSV became dependent on the protease to process two of its genes. We then applied selective pressure with nirmatrelvir to induce mutations. The effect of those mutants was confirmed by re-introduction in the 3CLpro and testing with a recently developed cellular assay. Furthermore, we found that mutations predicted by our method already exist in SARS-CoV-2 sequence depositions in NCBI and GISAID data bases. These may represent emerging resistant virus variants or a natural heterogeneity in the susceptibility to nirmatrelvir. One-Sentence Summary Mutations of the main protease of SARS-CoV-2 result in resistance against licensed drugs such as Paxlovid (nirmatrelvir / ritonavir). Graphical abstract" @default.
- W4283806747 created "2022-07-06" @default.
- W4283806747 creator A5043031636 @default.
- W4283806747 creator A5044697154 @default.
- W4283806747 creator A5047271069 @default.
- W4283806747 creator A5075857776 @default.
- W4283806747 date "2022-07-04" @default.
- W4283806747 modified "2023-10-11" @default.
- W4283806747 title "SARS-CoV-2 3CLpro mutations confer resistance to Paxlovid (nirmatrelvir/ritonavir) in a VSV-based, non-gain-of-function system" @default.
- W4283806747 cites W1969323021 @default.
- W4283806747 cites W1971439989 @default.
- W4283806747 cites W1989069389 @default.
- W4283806747 cites W1998139623 @default.
- W4283806747 cites W2128955394 @default.
- W4283806747 cites W2146397496 @default.
- W4283806747 cites W2525631210 @default.
- W4283806747 cites W2559258718 @default.
- W4283806747 cites W2587970647 @default.
- W4283806747 cites W2605343262 @default.
- W4283806747 cites W3094021184 @default.
- W4283806747 cites W3121995178 @default.
- W4283806747 cites W3189646261 @default.
- W4283806747 cites W3199620752 @default.
- W4283806747 cites W4200137031 @default.
- W4283806747 cites W4212949239 @default.
- W4283806747 cites W4220921077 @default.
- W4283806747 cites W4224952045 @default.
- W4283806747 doi "https://doi.org/10.1101/2022.07.02.495455" @default.
- W4283806747 hasPublicationYear "2022" @default.
- W4283806747 type Work @default.
- W4283806747 citedByCount "9" @default.
- W4283806747 countsByYear W42838067472022 @default.
- W4283806747 countsByYear W42838067472023 @default.
- W4283806747 crossrefType "posted-content" @default.
- W4283806747 hasAuthorship W4283806747A5043031636 @default.
- W4283806747 hasAuthorship W4283806747A5044697154 @default.
- W4283806747 hasAuthorship W4283806747A5047271069 @default.
- W4283806747 hasAuthorship W4283806747A5075857776 @default.
- W4283806747 hasBestOaLocation W42838067471 @default.
- W4283806747 hasConcept C104317684 @default.
- W4283806747 hasConcept C142462285 @default.
- W4283806747 hasConcept C143065580 @default.
- W4283806747 hasConcept C159047783 @default.
- W4283806747 hasConcept C181199279 @default.
- W4283806747 hasConcept C2522874641 @default.
- W4283806747 hasConcept C2776714187 @default.
- W4283806747 hasConcept C2779298103 @default.
- W4283806747 hasConcept C2781143361 @default.
- W4283806747 hasConcept C2993143319 @default.
- W4283806747 hasConcept C54355233 @default.
- W4283806747 hasConcept C55493867 @default.
- W4283806747 hasConcept C86803240 @default.
- W4283806747 hasConceptScore W4283806747C104317684 @default.
- W4283806747 hasConceptScore W4283806747C142462285 @default.
- W4283806747 hasConceptScore W4283806747C143065580 @default.
- W4283806747 hasConceptScore W4283806747C159047783 @default.
- W4283806747 hasConceptScore W4283806747C181199279 @default.
- W4283806747 hasConceptScore W4283806747C2522874641 @default.
- W4283806747 hasConceptScore W4283806747C2776714187 @default.
- W4283806747 hasConceptScore W4283806747C2779298103 @default.
- W4283806747 hasConceptScore W4283806747C2781143361 @default.
- W4283806747 hasConceptScore W4283806747C2993143319 @default.
- W4283806747 hasConceptScore W4283806747C54355233 @default.
- W4283806747 hasConceptScore W4283806747C55493867 @default.
- W4283806747 hasConceptScore W4283806747C86803240 @default.
- W4283806747 hasLocation W42838067471 @default.
- W4283806747 hasOpenAccess W4283806747 @default.
- W4283806747 hasPrimaryLocation W42838067471 @default.
- W4283806747 hasRelatedWork W1487857142 @default.
- W4283806747 hasRelatedWork W2025152688 @default.
- W4283806747 hasRelatedWork W2030228730 @default.
- W4283806747 hasRelatedWork W2030265729 @default.
- W4283806747 hasRelatedWork W2111958127 @default.
- W4283806747 hasRelatedWork W2117110650 @default.
- W4283806747 hasRelatedWork W2403949395 @default.
- W4283806747 hasRelatedWork W2405585042 @default.
- W4283806747 hasRelatedWork W2405775250 @default.
- W4283806747 hasRelatedWork W2603476049 @default.
- W4283806747 isParatext "false" @default.
- W4283806747 isRetracted "false" @default.
- W4283806747 workType "article" @default.