FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3205433765> ?p ?o ?g. }

• W3205433765 endingPage "105190" @default.
• W3205433765 startingPage "105190" @default.
• W3205433765 abstract "Although the seroprevalence of Herpes simplex virus type 1 (HSV-1) currently amounts to ∼ 67% worldwide, the annual incidence of a severe disease progression, particularly herpes encephalitis, is approximately 2–4 cases per 1,000,000 infections. Nucleoside analogues, such as acyclovir (ACV), valacyclovir (VACV) or famciclovir, are still the therapeutic treatment of choice for HSV infections. However, nucleoside drugs have limited efficacy against severe HSV disease and for treatment of nucleoside-resistant viral strains, alternative therapies such as helicase-primase inhibitors (HPIs) which are highly potent by inhibiting viral replication are under development. In preclinical studies we analyzed the antiviral efficacy of drug candidates of a novel compound class of HPIs for the treatment of HSV to identify the most active eutomer structure in an intranasal infection mouse lethal challenge model. HSV-1 infected BALB/c mice treated with vehicle control developed fatal disease according to humane endpoints after 5–7 days. In contrast, the animals dosed orally once daily with the HPI compounds at 10 or 4 mg/kg/day showed a significantly increased survival (70% and 100% for 10 mg/kg/day; 90% and 100% for 4 mg/kg/day, respectively) compared to the vehicle treatment (0–10%), when therapy was initiated 6 h post HSV-1 inoculation. We observed a significantly improved outcome in clinical parameters and survival over 21 days in the group receiving novel HPI candidates using even the lowest dose of 4 mg/kg/day. With VACV treatment of 75 mg/kg daily survival was also significantly increased (80%–90% for 75 mg/kg/day) but to lesser extent. Initial IM-250 therapy at 10 mg/kg/day could be delayed up to 72 h resulting in significantly increased survival compared to the vehicle control. Furthermore, we detected significantly fewer viral genome copies in the lungs and brains of HPI treated animals compared to vehicle (440-fold reduction for 4 mg/kg/day IM-250 in the brain) or VACV controls by quantitative PCR. In conclusion the preclinical studies of the novel HPI compounds showed superior efficacy in comparison to the current standard HSV treatment represented by VACV with respect to the survival according humane endpoints, the clinical score and virus load in lungs and brains. Thus, candidates of this new drug class are promising antivirals of HSV infections and further translation into clinical trials is warranted." @default.
• W3205433765 created "2021-10-25" @default.
• W3205433765 creator A5009204590 @default.
• W3205433765 creator A5013972886 @default.
• W3205433765 creator A5035703144 @default.
• W3205433765 creator A5035991850 @default.
• W3205433765 creator A5038087675 @default.
• W3205433765 creator A5038299114 @default.
• W3205433765 date "2021-11-01" @default.
• W3205433765 modified "2023-09-25" @default.
• W3205433765 title "Helicase primase inhibitors (HPIs) are efficacious for therapy of human herpes simplex virus (HSV) disease in an infection mouse model" @default.
• W3205433765 cites W1521918462 @default.
• W3205433765 cites W1539384503 @default.
• W3205433765 cites W1970142451 @default.
• W3205433765 cites W1975418639 @default.
• W3205433765 cites W1981412199 @default.
• W3205433765 cites W2004584518 @default.
• W3205433765 cites W2019405166 @default.
• W3205433765 cites W2027289172 @default.
• W3205433765 cites W2031659539 @default.
• W3205433765 cites W2035471594 @default.
• W3205433765 cites W2043158748 @default.
• W3205433765 cites W2043841254 @default.
• W3205433765 cites W2045360603 @default.
• W3205433765 cites W2053611532 @default.
• W3205433765 cites W2064587156 @default.
• W3205433765 cites W2081007549 @default.
• W3205433765 cites W2090634114 @default.
• W3205433765 cites W2090765690 @default.
• W3205433765 cites W2102715326 @default.
• W3205433765 cites W2110002916 @default.
• W3205433765 cites W2113548117 @default.
• W3205433765 cites W2114066593 @default.
• W3205433765 cites W2120911201 @default.
• W3205433765 cites W2122452548 @default.
• W3205433765 cites W2137186878 @default.
• W3205433765 cites W2153520257 @default.
• W3205433765 cites W2162317223 @default.
• W3205433765 cites W2163761927 @default.
• W3205433765 cites W2167540878 @default.
• W3205433765 cites W2275987487 @default.
• W3205433765 cites W2286343792 @default.
• W3205433765 cites W2318381801 @default.
• W3205433765 cites W2326308721 @default.
• W3205433765 cites W2562795102 @default.
• W3205433765 cites W2565394836 @default.
• W3205433765 cites W2766523073 @default.
• W3205433765 cites W3172699374 @default.
• W3205433765 doi "https://doi.org/10.1016/j.antiviral.2021.105190" @default.
• W3205433765 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34666109" @default.
• W3205433765 hasPublicationYear "2021" @default.
• W3205433765 type Work @default.
• W3205433765 sameAs 3205433765 @default.
• W3205433765 citedByCount "7" @default.
• W3205433765 countsByYear W32054337652022 @default.
• W3205433765 countsByYear W32054337652023 @default.
• W3205433765 crossrefType "journal-article" @default.
• W3205433765 hasAuthorship W3205433765A5009204590 @default.
• W3205433765 hasAuthorship W3205433765A5013972886 @default.
• W3205433765 hasAuthorship W3205433765A5035703144 @default.
• W3205433765 hasAuthorship W3205433765A5035991850 @default.
• W3205433765 hasAuthorship W3205433765A5038087675 @default.
• W3205433765 hasAuthorship W3205433765A5038299114 @default.
• W3205433765 hasBestOaLocation W32054337651 @default.
• W3205433765 hasConcept C104317684 @default.
• W3205433765 hasConcept C12914427 @default.
• W3205433765 hasConcept C156719811 @default.
• W3205433765 hasConcept C159047783 @default.
• W3205433765 hasConcept C194830204 @default.
• W3205433765 hasConcept C203014093 @default.
• W3205433765 hasConcept C2522874641 @default.
• W3205433765 hasConcept C2776723293 @default.
• W3205433765 hasConcept C2781196997 @default.
• W3205433765 hasConcept C55493867 @default.
• W3205433765 hasConcept C67705224 @default.
• W3205433765 hasConcept C71924100 @default.
• W3205433765 hasConcept C86803240 @default.
• W3205433765 hasConcept C98274493 @default.
• W3205433765 hasConceptScore W3205433765C104317684 @default.
• W3205433765 hasConceptScore W3205433765C12914427 @default.
• W3205433765 hasConceptScore W3205433765C156719811 @default.
• W3205433765 hasConceptScore W3205433765C159047783 @default.
• W3205433765 hasConceptScore W3205433765C194830204 @default.
• W3205433765 hasConceptScore W3205433765C203014093 @default.
• W3205433765 hasConceptScore W3205433765C2522874641 @default.
• W3205433765 hasConceptScore W3205433765C2776723293 @default.
• W3205433765 hasConceptScore W3205433765C2781196997 @default.
• W3205433765 hasConceptScore W3205433765C55493867 @default.
• W3205433765 hasConceptScore W3205433765C67705224 @default.
• W3205433765 hasConceptScore W3205433765C71924100 @default.
• W3205433765 hasConceptScore W3205433765C86803240 @default.
• W3205433765 hasConceptScore W3205433765C98274493 @default.
• W3205433765 hasLocation W32054337651 @default.
• W3205433765 hasLocation W32054337652 @default.
• W3205433765 hasOpenAccess W3205433765 @default.
• W3205433765 hasPrimaryLocation W32054337651 @default.
• W3205433765 hasRelatedWork W1993339219 @default.
• W3205433765 hasRelatedWork W2038801503 @default.

• next