Matches in SemOpenAlex for { <https://semopenalex.org/work/W4224324150> ?p ?o ?g. }
- W4224324150 endingPage "104293" @default.
- W4224324150 startingPage "104293" @default.
- W4224324150 abstract "The nucleoside analog N4-hydroxycytidine (NHC) is the active metabolite of the prodrug molnupiravir, which has been approved for the treatment of COVID-19. SARS-CoV-2 incorporates NHC into its RNA, resulting in defective virus genomes. Likewise, inhibitors of dihydroorotate dehydrogenase (DHODH) reduce virus yield upon infection, by suppressing the cellular synthesis of pyrimidines. Here, we show that NHC and DHODH inhibitors strongly synergize in the inhibition of SARS-CoV-2 replication in vitro. We propose that the lack of available pyrimidine nucleotides upon DHODH inhibition increases the incorporation of NHC into nascent viral RNA. This concept is supported by the rescue of virus replication upon addition of pyrimidine nucleosides to the media. DHODH inhibitors increased the antiviral efficiency of molnupiravir not only in organoids of human lung, but also in Syrian Gold hamsters and in K18-hACE2 mice. Combining molnupiravir with DHODH inhibitors may thus improve available therapy options for COVID-19." @default.
- W4224324150 created "2022-04-26" @default.
- W4224324150 creator A5002574795 @default.
- W4224324150 creator A5004540529 @default.
- W4224324150 creator A5006815276 @default.
- W4224324150 creator A5008136539 @default.
- W4224324150 creator A5011041473 @default.
- W4224324150 creator A5013972886 @default.
- W4224324150 creator A5014889492 @default.
- W4224324150 creator A5015543699 @default.
- W4224324150 creator A5032855931 @default.
- W4224324150 creator A5034905489 @default.
- W4224324150 creator A5035991850 @default.
- W4224324150 creator A5049218335 @default.
- W4224324150 creator A5050213096 @default.
- W4224324150 creator A5051265138 @default.
- W4224324150 creator A5056237696 @default.
- W4224324150 creator A5057181204 @default.
- W4224324150 creator A5061328421 @default.
- W4224324150 creator A5068515964 @default.
- W4224324150 creator A5068776922 @default.
- W4224324150 creator A5073546944 @default.
- W4224324150 creator A5078554885 @default.
- W4224324150 creator A5081001836 @default.
- W4224324150 creator A5082627042 @default.
- W4224324150 creator A5087322987 @default.
- W4224324150 creator A5091579356 @default.
- W4224324150 date "2022-05-01" @default.
- W4224324150 modified "2023-10-18" @default.
- W4224324150 title "Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication" @default.
- W4224324150 cites W1515293536 @default.
- W4224324150 cites W1970487533 @default.
- W4224324150 cites W1974756544 @default.
- W4224324150 cites W1975772219 @default.
- W4224324150 cites W1989069389 @default.
- W4224324150 cites W2009987166 @default.
- W4224324150 cites W2027535855 @default.
- W4224324150 cites W2037128099 @default.
- W4224324150 cites W2041422767 @default.
- W4224324150 cites W2041811148 @default.
- W4224324150 cites W2043343078 @default.
- W4224324150 cites W2050674793 @default.
- W4224324150 cites W2060737851 @default.
- W4224324150 cites W2069445877 @default.
- W4224324150 cites W2076435302 @default.
- W4224324150 cites W2078627161 @default.
- W4224324150 cites W2092911406 @default.
- W4224324150 cites W2120649647 @default.
- W4224324150 cites W2125462233 @default.
- W4224324150 cites W2127459073 @default.
- W4224324150 cites W2139086828 @default.
- W4224324150 cites W2142094474 @default.
- W4224324150 cites W2189487392 @default.
- W4224324150 cites W2312482418 @default.
- W4224324150 cites W2481374159 @default.
- W4224324150 cites W2582590404 @default.
- W4224324150 cites W2594626196 @default.
- W4224324150 cites W2807193652 @default.
- W4224324150 cites W2913551559 @default.
- W4224324150 cites W2945440984 @default.
- W4224324150 cites W2979108578 @default.
- W4224324150 cites W2981723136 @default.
- W4224324150 cites W2996962570 @default.
- W4224324150 cites W3001195213 @default.
- W4224324150 cites W3014482292 @default.
- W4224324150 cites W3014708904 @default.
- W4224324150 cites W3020947166 @default.
- W4224324150 cites W3023162001 @default.
- W4224324150 cites W3027630905 @default.
- W4224324150 cites W3028150847 @default.
- W4224324150 cites W3028402548 @default.
- W4224324150 cites W3031410383 @default.
- W4224324150 cites W3032677067 @default.
- W4224324150 cites W3036887118 @default.
- W4224324150 cites W3045503594 @default.
- W4224324150 cites W3047125225 @default.
- W4224324150 cites W3082108964 @default.
- W4224324150 cites W3085591857 @default.
- W4224324150 cites W3107191813 @default.
- W4224324150 cites W3108974439 @default.
- W4224324150 cites W3109110891 @default.
- W4224324150 cites W3110209099 @default.
- W4224324150 cites W3111458826 @default.
- W4224324150 cites W3112281188 @default.
- W4224324150 cites W3112902030 @default.
- W4224324150 cites W3119415300 @default.
- W4224324150 cites W3126546961 @default.
- W4224324150 cites W3135383916 @default.
- W4224324150 cites W3135540980 @default.
- W4224324150 cites W3139503800 @default.
- W4224324150 cites W3153317009 @default.
- W4224324150 cites W3154750958 @default.
- W4224324150 cites W3157786842 @default.
- W4224324150 cites W3161345526 @default.
- W4224324150 cites W3163488943 @default.
- W4224324150 cites W3172520795 @default.
- W4224324150 cites W3178036525 @default.
- W4224324150 cites W3180181011 @default.