Synthesis and antiviral evaluation of 2′,2′,3′,3′-tetrafluoro nucleoside analogs

Sari, Ozkan; Bassit, Leda; Gavegnano, Christina; McBrayer, Tamara R.; McCormick, Louise; Cox, Bryan; Coats, Steven J.; Amblard, Franck; Schinazi, Raymond F.

doi:10.1016/j.tetlet.2017.01.006

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…Nucleoside analogs. Nucleoside derivatives (designated compounds 1 to 14) were synthesized in our laboratory according to previously reported procedures (29,(40)(41)(42)(43)(44)(45) and were at least 95% pure, as estimated by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) analyses. Chemical structures for compounds 1 to 14 are summarized in Fig.…”

Section: Methodsmentioning

confidence: 99%

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Zandi

Bassit

Amblard

et al. 2019

Antimicrob Agents Chemother

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Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2=-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.KEYWORDS Dengue virus, Japanese encephalitis virus, antiviral agents, nucleoside analogs D engue virus (DENV) and Japanese encephalitis virus (JEV) are members of the genus Flavivirus, belonging to the family Flaviviridae. Many flaviviruses are arthropod borne and cause severe infections in humans and vertebrate animals. DENV has four serotypes (DENV-1 to DENV-4), which collectively pose a health threat to 2.5 billion people worldwide, with 50 million to 100 million human infections and 500,000 cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) annually (1-3). JEV is one of the most important neurotropic flaviviruses that causes encephalitis in humans. Symptoms range from mild febrile illness to mortal illness, especially in children, with about 67,900 cases each year (4). JEV is endemic in eastern and southern Asia (including China, Indonesia, Nepal, Thailand, Saipan Island, Pakistan, and the Torres Strait) and Australia, with fatality rates of 20% to 30% and life-long neurological impairments and sequelae among one-half of the survivors (5-8). Despite a licensed vaccine to prevent JEV infection, infections occur annually due to a lack of complete coverage and access (9). A tetravalent DENV vaccine also exists but remains partially on July 10, 2020 by guest http://aac.asm.org/ Downloaded fromArg474. The triphosphate group forms electrostatic interactions with Arg474, Lys694, and two active site Mn 2ϩ ions.Nucleoside inhibitors of DENV. The same 14 nucleoside analogs were assayed against DENV using a BHK-21 cell line harboring the...

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Section: Methodsmentioning

confidence: 99%

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Zandi

Bassit

Amblard

et al. 2019

Antimicrob Agents Chemother

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“…Carbohydrate derivatives such as swainsonine [71,72], 1,4-dideoxy-1,4-imino-D-mannitol [73], deoxymannojirimycin [74,75], and castanospermine [76,77] have shown anticancer activity in different cancer types. Nucleoside analogs are well-developed antiviral drugs for many viral infections including HIV, HBV, dengue virus, yellow fever virus, JEV, and Zika virus [78][79][80]. According to our findings from the solution carbohydrate microarray, the SARS-CoV-2 spike protein S1 subunit preferentially binds to blood group A/B antigens and specific terminal sugar moieties including galactose, N-acetylgalactosamine, and sulfated galactose.…”

Section: Discussionmentioning

confidence: 88%

Carbohydrate Ligands for COVID-19 Spike Proteins

Lee

Chang

Prakash

et al. 2022

Viruses

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An outbreak of SARS-CoV-2 coronavirus (COVID-19) first detected in Wuhan, China, has created a public health emergency all over the world. The pandemic has caused more than 340 million confirmed cases and 5.57 million deaths as of 23 January 2022. Although carbohydrates have been found to play a role in coronavirus binding and infection, the role of cell surface glycans in SARS-CoV-2 infection and pathogenesis is still not understood. Herein, we report that the SARS-CoV-2 spike protein S1 subunit binds specifically to blood group A and B antigens, and that the spike protein S2 subunit has a binding preference for Lea antigens. Further examination of the binding preference for different types of red blood cells (RBCs) indicated that the spike protein S1 subunit preferentially binds with blood group A RBCs, whereas the spike protein S2 subunit prefers to interact with blood group Lea RBCs. Angiotensin converting enzyme 2 (ACE2), a known target of SARS-CoV-2 spike proteins, was identified to be a blood group A antigen-containing glycoprotein. Additionally, 6-sulfo N-acetyllactosamine was found to inhibit the binding of the spike protein S1 subunit with blood group A RBCs and reduce the interaction between the spike protein S1 subunit and ACE2.

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“…Recently, Schinazi and co‐workers demonstrated the utility of pentose 79 (Scheme ) as a precursor of fluorinated nucleosides 118a – e and their phosphoramidate prodrug derivatives 119a – e (Scheme ) . Tests against several viruses (HIV‐1, HBV, HCV, Ebola, Zika) did not reveal any significant antiviral activity.…”

Section: Applications Of Cf2cf2‐containing Compoundsmentioning

confidence: 99%

“…The importance of fluorinated pharmaceuticals has been well documented . Some biological studies involving the CF 2 CF 2 ‐contatining compounds have already been mentioned in the context of fluorinated sugars (Chapter 4.2), such as novel antituberculosis agents (Figure ), or antiviral candidates (Scheme ) …”

Section: Applications Of Cf2cf2‐containing Compoundsmentioning

confidence: 99%

Advances in the Synthesis and Application of Tetrafluoroethylene‐ and 1,1,2,2‐Tetrafluoroethyl‐Containing Compounds

et al. 2018

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In this review, we provide a comprehensive and critical perspective on the synthesis and application of 1,1,2,2‐tetrafluoroethyl‐ and tetrafluoroethylene‐containing compounds. These structures have been the focus of increasing attention as witnessed by a spectrum of new synthetic approaches, which have recently appeared in the literature. Likewise, applications of molecules containing the CF2CF2 fragment as pharmaceuticals, agrochemicals, pesticides, and advanced materials are described. It is expected that the number of successful applications of these compounds will increase in the future as a result of availability of the synthetic methods outlined here.

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Synthesis and antiviral evaluation of 2′,2′,3′,3′-tetrafluoro nucleoside analogs

Cited by 10 publications

References 22 publications

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Carbohydrate Ligands for COVID-19 Spike Proteins

Advances in the Synthesis and Application of Tetrafluoroethylene‐ and 1,1,2,2‐Tetrafluoroethyl‐Containing Compounds

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