Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• of the Czech Academy of Sciences, Flemingovo náměstí 542/2, 166 10 Prague, Czech Republic 10.3762/bjoc.20.91 Abstract The RNA-dependent RNA polymerase (RdRp) represents a prominent target in the discovery and development of new antivirotics against RNA viruses, inhibiting the replication process

• : antivirotics; nonnucleotide inhibitor; RNA-dependent RNA polymerase; SARS-CoV-2; Introduction Epidemics caused by various viral infections, such as AIDS, Zika fever, Dengue fever, or Ebola, are a constant threat to communities of all sizes [1]. The COVID-19 pandemic, caused by the newly emerged severe acute

• directly act as a viral messenger RNA and encodes essential enzymes for replication [3]. Inhibiting these nonstructural proteins that are part of the replication complex has already shown great success in antiviral therapy [4][5][6][7]. The viral RNA-dependent RNA polymerase (RdRp) is encoded in all RNA

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• , Figure 1), is one of the few licensed drugs for treating RSV infections [8][9]. Although there are many suggested mechanisms of action, the main mechanisms for RBV involve the inhibition of the enzymes RNA-dependent RNA polymerase and inosine monophosphate dehydrogenase (IMPDH). IMPDH is required for the

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• summary, these primitive enzymes associated an RNA molecule capable of catalysing peptide-bond formation (the ancestor of the ribosomal RNA peptidyl transferase centre) and the resulting protein functioning as an RNA-dependent RNA polymerase [64]. Today, and this is further evidence of early roles of

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• -lines [14][15][16]. Moreover, some 6-heterocyclic substituted purine ribonucleosides also demonstrate strong antiviral activities [17]. Purine derivatives such as, 2’-β-C-methyl-6-substituted purine nucleosides exhibit promising anti-HCV activity by blocking RNA dependent RNA polymerase [18][19][20

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• as NS2, NS3 (which bear serine proteinase, helicase, and NTPase activities), NS4A, NS4B, NS5A (regulators of RNA replication), and NS5B (the RNA-dependent RNA polymerase) are generated [2][3] and, in fact, constitute the main targets. At the moment, there are many drugs under clinical trial

• inhibit the RNA-dependent RNA polymerase of the virus responsible for hepatitis C (genotype 1g) [5]. Thus, their high replication rates (billions of copies per day) can be drastically suppressed by the inhibition of the NS5B RNA-dependent RNA polymerase enzyme, which is the primary target for oral