Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication was written by Stegmann, Kim M.;Dickmanns, Antje;Heinen, Natalie;Blaurock, Claudia;Karrasch, Tim;Breithaupt, Angele;Klopfleisch, Robert;Uhlig, Nadja;Eberlein, Valentina;Issmail, Leila;Herrmann, Simon T.;Schreieck, Amelie;Peelen, Evelyn;Kohlhof, Hella;Sadeghi, Balal;Riek, Alexander;Speakman, John R.;Gross, Uwe;Goerlich, Dirk;Vitt, Daniel;Mueller, Thorsten;Grunwald, Thomas;Pfaender, Stephanie;Balkema-Buschmann, Anne;Dobbelstein, Matthias. And the article was included in iScience in 2022.COA of Formula: C13H19N3O7 The following contents are mentioned in the article:
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. This study involved multiple reactions and reactants, such as ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5COA of Formula: C13H19N3O7).
((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5) belongs to tetrahydrofuran derivatives. THF (Tetrahydrofuran) is water-miscible and has a low viscosity making it a highly versatile solvent used in a variety of industries. THF can also be synthesized by catalytic hydrogenation of furan. This allows certain sugars to be converted to THF via acid-catalyzed digestion to furfural and decarbonylation to furan, although this method is not widely practiced. THF is thus derivable from renewable resources.COA of Formula: C13H19N3O7
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem