New conformationally locked bicyclic N,O-nucleoside analogues of antiviral drugs

2005 ◽  
Vol 15 (3) ◽  
pp. 545-550 ◽  
Author(s):  
Antonio Procopio ◽  
Stefano Alcaro ◽  
Antonio De Nino ◽  
Loredana Maiuolo ◽  
Francesco Ortuso ◽  
...  
ChemInform ◽  
2005 ◽  
Vol 36 (25) ◽  
Author(s):  
Antonio Procopio ◽  
Stefano Alcaro ◽  
Antonio De Nino ◽  
Loredana Maiuolo ◽  
Francesco Ortuso ◽  
...  

Author(s):  
Mohamed Ibrahim Elzagheid

: Nucleosides and their analogues have been in use for many years and have become essential for treating patients with viral infections. Many additional nucleoside drugs have been approved over the past decades. This strongly demonstrates how important these compounds are and the crucial role they play. Given that a significant amount of research and literature has been documented regarding nucleoside analogues, this review article mainly focuses the discussion on nucleosides and nucleoside analogous that have proven to play significant role or be emerging in the treatment of known viral infections. This covers the names, structures, applications, toxicity, and mode of action of relevant nucleoside analogues.


ChemInform ◽  
2012 ◽  
Vol 43 (22) ◽  
pp. no-no
Author(s):  
Milan Dejmek ◽  
Hubert Hrebabecky ◽  
Martin Dracinsky ◽  
Johan Neyts ◽  
Pieter Leyssen ◽  
...  

2011 ◽  
Vol 76 (12) ◽  
pp. 1549-1566 ◽  
Author(s):  
Milan Dejmek ◽  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Johan Neyts ◽  
Pieter Leyssen ◽  
...  

We report on the preparation of novel 1′-homonucleoside derivatives locked in a West conformation by 1′,4′-bridge consisting of annulated benzene or naphthalene ring. The crucial step of the synthesis was Diels–Alder reaction of an appropriate aryne with a suitable furane derivative. Antiviral properties of novel compounds were studied and slight activity against HCV was detected in several compounds.


1997 ◽  
Vol 328 (1) ◽  
pp. 317-320 ◽  
Author(s):  
Annalisa VERRI ◽  
Giuseppina PRIORI ◽  
Silvio SPADARI ◽  
Luisa TONDELLI ◽  
Federico FOCHER

Our discovery that Herpes virus thymidine kinase (TK) and cellular deoxycytidine kinase lack enantioselectivity, being able to phosphorylate both D- and L-enantiomers of the substrate, suggested the use of unnatural L-nucleoside analogues as antiviral drugs (Herpes, hepatitis and immunodeficiency viruses). Several L-nucleoside analogues have displayed a short-term cytotoxicity much lower than their corresponding D-counterpart. Since the delayed cytotoxicity of a drug often depends on its effects on mitochondrial metabolism, we have investigated the degree of enantioselectivity of human mitochondrial thymidine kinase (mt-TK). We demonstrate that mt-TK does not show an absolute enantioselectivity, being able to recognize, although with lower efficiency, the L-enantiomers of thymidine, deoxycytidine and modified deoxyuridines, such as (E)-5-(2-bromovinyl)-2ʹ-deoxyuridine and 5-iodo-2ʹ-deoxyuridine. Interestingly, the reported negative co-operativity of mt-TK phosphorylating β-D-2ʹ-deoxythymidine (D-Thd), disappears when the deoxyribose moiety has the inverted configuration, resulting in the preferential phosphorylation of D-Thd even in the presence of high concentrations of the L-enantiomer. This, coupled with the higher Km for β-l-2ʹ-deoxythymidine (L-Thd), makes mt-TK resistant to high concentrations of L-Thd and L-Thd analogues, minimizing the mitochondria-dependent delayed cytotoxicity that might be caused by the administration of l-nucleoside analogues as antivirals.


2016 ◽  
Vol 29 (3) ◽  
pp. 695-747 ◽  
Author(s):  
Erik De Clercq ◽  
Guangdi Li

SUMMARYSince the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2′-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2′-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.


Author(s):  
Qi Peng ◽  
Ruchao Peng ◽  
Bin Yuan ◽  
Min Wang ◽  
Jingru Zhao ◽  
...  

AbstractThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogues, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs against the newly emerging viral diseases. Recent clinical trials of these two drugs for SARS-CoV-2 treatment revealed antiviral efficacies as well as side effects with different extents1–4. As a pyrazine derivative, Favipiravir could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides, which may further lead to mutations in progeny RNA copies due to the non-conserved base-pairing capacity5. Here, we determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues which may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed lights on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.


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