Full Text Journal Articles by
Author Joy Y Feng

Advertisement

Find full text journal articles






Template-dependent inhibition of coronavirus RNA-dependent RNA polymerase by remdesivir reveals a second mechanism of action.

Egor P Tchesnokov, Calvin J Gordon, Emma Woolner, Dana Kocincova, Jason K Perry, Joy Y Feng, Danielle P Porter, Matthias Gotte,

Remdesivir (RDV) is a direct-acting antiviral agent that is used to treat patients with severe coronavirus disease 2019 (COVID-19). RDV targets the viral RNA-dependent RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have previously shown that incorporation of the active triphosphate form of RDV (RDV-TP) at ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice.

Andrea J Pruijssers, Amelia S George, Alexandra Schäfer, Sarah R Leist, Lisa E Gralinksi, Kenneth H Dinnon, Boyd L Yount, Maria L Agostini, Laura J Stevens, James D Chappell, Xiaotao Lu, Tia M Hughes, Kendra Gully, David R Martinez, Ariane J Brown, Rachel L Graham, Jason K Perry, Venice Du Pont, Jared Pitts, Bin Ma, Darius Babusis, Eisuke Murakami, Joy Y Feng, John P Bilello, Danielle P Porter, Tomas Cihlar, Ralph S Baric, Mark R Denison, Timothy P Sheahan,

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells ... Read more >>

Cell Rep (Cell reports)
[2020, 32(3):107940]

Cited: 0 times

View full text PDF listing >>



Advertisement

Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency.

Calvin J Gordon, Egor P Tchesnokov, Emma Woolner, Jason K Perry, Joy Y Feng, Danielle P Porter, Matthias Götte,

Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed to control this current pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV). RDV shows broad-spectrum ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2020, 295(20):6785-6797]

Cited: 25 times

View full text PDF listing >>



The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus.

Calvin J Gordon, Egor P Tchesnokov, Joy Y Feng, Danielle P Porter, Matthias Götte,

Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome-coronavirus 2 (CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including severe ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2020, 295(15):4773-4779]

Cited: 63 times

View full text PDF listing >>



Biochemical characterization of tirabrutinib and other irreversible inhibitors of Bruton's tyrosine kinase reveals differences in on - and off - target inhibition.

Albert Liclican, Loredana Serafini, Weimei Xing, Gregg Czerwieniec, Bart Steiner, Ting Wang, Katherine M Brendza, Justin D Lutz, Kathleen S Keegan, Adrian S Ray, Brian E Schultz, Roman Sakowicz, Joy Y Feng,

BACKGROUND:Bruton's tyrosine kinase (BTK) is a key component of the B-cell receptor (BCR) pathway and a clinically validated target for small molecule inhibitors such as ibrutinib in the treatment of B-cell malignancies. Tirabrutinib (GS-4059/ONO-4059) is a selective, once daily, oral BTK inhibitor with clinical activity against many relapsed/refractory B-cell malignancies. ... Read more >>

Biochim Biophys Acta Gen Subj (Biochimica et biophysica acta. General subjects)
[2020, 1864(4):129531]

Cited: 1 time

View full text PDF listing >>



Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.

Timothy P Sheahan, Amy C Sims, Sarah R Leist, Alexandra Schäfer, John Won, Ariane J Brown, Stephanie A Montgomery, Alison Hogg, Darius Babusis, Michael O Clarke, Jamie E Spahn, Laura Bauer, Scott Sellers, Danielle Porter, Joy Y Feng, Tomas Cihlar, Robert Jordan, Mark R Denison, Ralph S Baric,

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):222]

Cited: 229 times

View full text PDF listing >>



Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.

Julie Farand, Jeffrey E Kropf, Peter Blomgren, Jianjun Xu, Aaron C Schmitt, Zachary E Newby, Ting Wang, Eisuke Murakami, Ona Barauskas, Jawahar Sudhamsu, Joy Y Feng, Anita Niedziela-Majka, Brian E Schultz, Karen Schwartz, Serge Viatchenko-Karpinski, Dmytro Kornyeyev, Adam Kashishian, Peidong Fan, Xiaowu Chen, Eric B Lansdon, Michael O Ports, Kevin S Currie, William J Watkins, Gregory T Notte,

We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation. Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM). Cocrystallization of 5 with MTH1 revealed the ... Read more >>

ACS Med Chem Lett (ACS medicinal chemistry letters)
[2020, 11(3):358-364]

Cited: 1 time

View full text PDF listing >>



Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase.

Ariane J Brown, John J Won, Rachel L Graham, Kenneth H Dinnon, Amy C Sims, Joy Y Feng, Tomas Cihlar, Mark R Denison, Ralph S Baric, Timothy P Sheahan,

The genetically diverse Orthocoronavirinae (CoV) family is prone to cross species transmission and disease emergence in both humans and livestock. Viruses similar to known epidemic strains circulating in wild and domestic animals further increase the probability of emergence in the future. Currently, there are no approved therapeutics for any human ... Read more >>

Antiviral Res. (Antiviral research)
[2019, 169:104541]

Cited: 47 times

View full text PDF listing >>



The KN-93 Molecule Inhibits Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity by Binding to Ca2+/CaM.

Melanie H Wong, Alexandra B Samal, Mike Lee, Jiri Vlach, Nikolai Novikov, Anita Niedziela-Majka, Joy Y Feng, Dmitry O Koltun, Katherine M Brendza, Hyock Joo Kwon, Brian E Schultz, Roman Sakowicz, Jamil S Saad, Giuseppe A Papalia,

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine protein kinase that transmits calcium signals in various cellular processes. CaMKII is activated by calcium-bound calmodulin (Ca2+/CaM) through a direct binding mechanism involving a regulatory C-terminal α-helix in CaMKII. The Ca2+/CaM binding triggers transphosphorylation of critical threonine residues proximal to the ... Read more >>

J. Mol. Biol. (Journal of molecular biology)
[2019, 431(7):1440-1459]

Cited: 3 times

View full text PDF listing >>



Nucleotide Prodrug Containing a Nonproteinogenic Amino Acid To Improve Oral Delivery of a Hepatitis C Virus Treatment.

Joy Y Feng, Ting Wang, Yeojin Park, Darius Babusis, Gabriel Birkus, Yili Xu, Christian Voitenleitner, Martijn Fenaux, Huiling Yang, Stacey Eng, Neeraj Tirunagari, Thorsten Kirschberg, Aesop Cho, Adrian S Ray,

Delivery of pharmacologically active nucleoside triphosphate analogs to sites of viral infection is challenging. In prior work we identified a 2'-C-methyl-1'-cyano-7-deaza-adenosine C-nucleotide analog with desirable selectivity and potency for the treatment of hepatitis C virus (HCV) infection. However, the prodrug selected for clinical development, GS-6620, required a high dose for ... Read more >>

Antimicrob. Agents Chemother. (Antimicrobial agents and chemotherapy)
[2018, 62(8):]

Cited: 0 times

View full text PDF listing >>



Homogeneous BTK Occupancy Assay for Pharmacodynamic Assessment of Tirabrutinib (GS-4059/ONO-4059) Target Engagement.

Helen Yu, Hoa Truong, Scott A Mitchell, Albert Liclican, John J Gosink, Wanying Li, Julie Lin, Joy Y Feng, Juliane M Jürgensmeier, Andrew Billin, Ren Xu, Scott Patterson, Nikos Pagratis,

Bruton's tyrosine kinase (BTK) is a clinically validated target for B-cell leukemias and lymphomas with FDA-approved small-molecule inhibitors ibrutinib and acalabrutinib. Tirabrutinib (GS-4059/ONO-4059, Gilead Sciences, Inc., Foster City, CA) is a second-generation, potent, selective, irreversible BTK inhibitor in clinical development for lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse ... Read more >>

SLAS Discov (SLAS discovery : advancing life sciences R & D)
[2018, 23(9):919-929]

Cited: 0 times

View full text PDF listing >>



Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease.

Maria L Agostini, Erica L Andres, Amy C Sims, Rachel L Graham, Timothy P Sheahan, Xiaotao Lu, Everett Clinton Smith, James Brett Case, Joy Y Feng, Robert Jordan, Adrian S Ray, Tomas Cihlar, Dustin Siegel, Richard L Mackman, Michael O Clarke, Ralph S Baric, Mark R Denison,

Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a ... Read more >>

mBio (mBio)
[2018, 9(2):]

Cited: 144 times

View full text PDF listing >>



Addressing the selectivity and toxicity of antiviral nucleosides.

Joy Y Feng,

Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, ... Read more >>

Antivir. Chem. Chemother. (Antiviral chemistry & chemotherapy)
[2018, 26:2040206618758524]

Cited: 5 times

View full text PDF listing >>



Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses.

Timothy P Sheahan, Amy C Sims, Rachel L Graham, Vineet D Menachery, Lisa E Gralinski, James B Case, Sarah R Leist, Krzysztof Pyrc, Joy Y Feng, Iva Trantcheva, Roy Bannister, Yeojin Park, Darius Babusis, Michael O Clarke, Richard L Mackman, Jamie E Spahn, Christopher A Palmiotti, Dustin Siegel, Adrian S Ray, Tomas Cihlar, Robert Jordan, Mark R Denison, Ralph S Baric,

Emerging viral infections are difficult to control because heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. Severe acute respiratory syndrome CoV (SARS-CoV) ... Read more >>

Sci Transl Med (Science translational medicine)
[2017, 9(396):]

Cited: 175 times

View full text PDF listing >>



Discovery of a 2'-fluoro-2'-C-methyl C-nucleotide HCV polymerase inhibitor and a phosphoramidate prodrug with favorable properties.

Thorsten A Kirschberg, Sammy Metobo, Michael O Clarke, Vangelis Aktoudianakis, Darius Babusis, Ona Barauskas, Gabriel Birkus, Thomas Butler, Daniel Byun, Gregory Chin, Edward Doerffler, Thomas E Edwards, Martijn Fenaux, Rick Lee, Willard Lew, Michael R Mish, Eisuke Murakami, Yeojin Park, Neil H Squires, Neeraj Tirunagari, Ting Wang, Mark Whitcomb, Jie Xu, Huiling Yang, Hong Ye, Lijun Zhang, Todd C Appleby, Joy Y Feng, Adrian S Ray, Aesop Cho, Choung U Kim,

A series of 2'-fluorinated C-nucleosides were prepared and tested for anti-HCV activity. Among them, the triphosphate of 2'-fluoro-2'-C-methyl adenosine C-nucleoside (15) was a potent and selective inhibitor of the NS5B polymerase and maintained activity against the S282T resistance mutant. A number of phosphoramidate prodrugs were then prepared and evaluated leading ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & Medicinal Chemistry Letters)
[2017, 27(8):1840-1847]

Cited: 0 times

View full text PDF listing >>



Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.

Dustin Siegel, Hon C Hui, Edward Doerffler, Michael O Clarke, Kwon Chun, Lijun Zhang, Sean Neville, Ernest Carra, Willard Lew, Bruce Ross, Queenie Wang, Lydia Wolfe, Robert Jordan, Veronica Soloveva, John Knox, Jason Perry, Michel Perron, Kirsten M Stray, Ona Barauskas, Joy Y Feng, Yili Xu, Gary Lee, Arnold L Rheingold, Adrian S Ray, Roy Bannister, Robert Strickley, Swami Swaminathan, William A Lee, Sina Bavari, Tomas Cihlar, Michael K Lo, Travis K Warren, Richard L Mackman,

The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2017, 60(5):1648-1661]

Cited: 64 times

View full text PDF listing >>



Role of Mitochondrial Toxicity in BMS-986094-Induced Toxicity.

Joy Y Feng, Chin H Tay, Adrian S Ray,

Toxicol. Sci. (Toxicological sciences : an official journal of the Society of Toxicology)
[2017, 155(1):2]

Cited: 3 times

View full text PDF listing >>



Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

Travis K Warren, Robert Jordan, Michael K Lo, Adrian S Ray, Richard L Mackman, Veronica Soloveva, Dustin Siegel, Michel Perron, Roy Bannister, Hon C Hui, Nate Larson, Robert Strickley, Jay Wells, Kelly S Stuthman, Sean A Van Tongeren, Nicole L Garza, Ginger Donnelly, Amy C Shurtleff, Cary J Retterer, Dima Gharaibeh, Rouzbeh Zamani, Tara Kenny, Brett P Eaton, Elizabeth Grimes, Lisa S Welch, Laura Gomba, Catherine L Wilhelmsen, Donald K Nichols, Jonathan E Nuss, Elyse R Nagle, Jeffrey R Kugelman, Gustavo Palacios, Edward Doerffler, Sean Neville, Ernest Carra, Michael O Clarke, Lijun Zhang, Willard Lew, Bruce Ross, Queenie Wang, Kwon Chun, Lydia Wolfe, Darius Babusis, Yeojin Park, Kirsten M Stray, Iva Trancheva, Joy Y Feng, Ona Barauskas, Yili Xu, Pamela Wong, Molly R Braun, Mike Flint, Laura K McMullan, Shan-Shan Chen, Rachel Fearns, Swami Swaminathan, Douglas L Mayers, Christina F Spiropoulou, William A Lee, Stuart T Nichol, Tomas Cihlar, Sina Bavari,

The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. ... Read more >>

Nature (Nature)
[2016, 531(7594):381-385]

Cited: 229 times

View full text PDF listing >>



Synthesis and characterization of 1'-C-cyano-2'-fluoro-2'-C-methyl pyrimidine nucleosides as HCV polymerase inhibitors.

Thorsten A Kirschberg, Michael R Mish, Lijun Zhang, Neil H Squires, Ke-Yu Wang, Aesop Cho, Joy Y Feng, Martijn Fenaux, Darius Babusis, Yeojin Park, Adrian S Ray, Choung U Kim,

The first synthesis of 1'-C-CN, 2'-F, 2'-C-Me pyrimidines is described. Anti-HCV activity was assessed and compared to the 1'-C-CN, 2'-C-Me as well as the 2'-F, 2'-C-Me pyrimidines. A phosphoramidate prodrug of the cytidine derivative showed activity in the low micromolar range against HCV replicons. ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & Medicinal Chemistry Letters)
[2015, 25(5):1040-1043]

Cited: 1 time

View full text PDF listing >>



Preparation and biological evaluation of 1'-cyano-2'-C-methyl pyrimidine nucleosides as HCV NS5B polymerase inhibitors.

Michael R Mish, Aesop Cho, Thorsten Kirschberg, Jie Xu, C Sebastian Zonte, Martijn Fenaux, Yeojin Park, Darius Babusis, Joy Y Feng, Adrian S Ray, Choung U Kim,

The first synthesis of 1'-cyano-2'-C-methyl pyrimidine nucleosides is described. Anti-HCV activity of these nucleosides and their nucleotide phosphoramidate prodrugs was assessed and compared to the 1'-unsubstituted counterparts and to the related 1'-cyano-2'-C-methyl C-nucleoside parent of GS-6620. ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & Medicinal Chemistry Letters)
[2014, 24(14):3092-3095]

Cited: 4 times

View full text PDF listing >>



Dead-end complexes contribute to the synergistic inhibition of HIV-1 RT by the combination of rilpivirine, emtricitabine, and tenofovir.

Rima Kulkarni, Joy Y Feng, Michael D Miller, Kirsten L White,

The single tablet regimen of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is approved for the treatment of HIV-1 infection in treatment-naïve adults. Previous studies have shown that two-drug combinations of these drugs show additive to ... Read more >>

Antiviral Res. (Antiviral research)
[2014, 101:131-135]

Cited: 3 times

View full text PDF listing >>



Evaluation of 2'-α-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase.

Jay P Parrish, Sharon K Lee, Constantine G Boojamra, Hon Hui, Darius Babusis, Brandon Brown, I-hung Shih, Joy Y Feng, Adrian S Ray, Richard L Mackman,

Ribonucleoside phosphonate analogues containing 2'-α-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase. The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1.9-2.1 μM, but only modest cell-based activity in the HCV replicon. Pro-drugs of the parent ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & Medicinal Chemistry Letters)
[2013, 23(11):3354-3357]

Cited: 2 times

View full text PDF listing >>



Bifunctional inhibition of HIV-1 reverse transcriptase: a first step in designing a bifunctional triphosphate.

Dongyuan Piao, Aravind Basavapathruni, Pinar Iyidogan, Guangxiu Dai, Wolfgang Hinz, Adrian S Ray, Eisuke Murakami, Joy Y Feng, Fei You, Ginger E Dutschman, David J Austin, Kathlyn A Parker, Karen S Anderson,

The onset of resistance to approved anti-AIDS drugs by HIV necessitates the search for novel inhibitors of HIV-1 reverse transcriptase (RT). Developing single molecular agents concurrently occupying the nucleoside and nonnucleoside binding sites in RT is an intriguing idea but the proof of concept has so far been elusive. As ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2013, 23(5):1511-1518]

Cited: 3 times

View full text PDF listing >>



Synthesis and characterization of 2'-C-Me branched C-nucleosides as HCV polymerase inhibitors.

Aesop Cho, Lijun Zhang, Jie Xu, Darius Babusis, Thomas Butler, Rick Lee, Oliver L Saunders, Ting Wang, Jay Parrish, Jason Perry, Joy Y Feng, Adrian S Ray, Choung U Kim,

A series of 2'-C-methyl branched purine and pyrimidine C-nucleosides were prepared. Their anti-HCV activity and pharmacological properties were profiled, and compared with known 2'-C-Me N-nucleoside counterparts. In particular, 2'-C-Me 4-aza-7,9-dideazaadenosine C-nucleoside (2) was found to have potent and selective anti-HCV activity in vitro as well as a favorable pharmacokinetic profile ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & Medicinal Chemistry Letters)
[2012, 22(12):4127-4132]

Cited: 11 times

View full text PDF listing >>



Synthesis and antiviral activity of a series of 1'-substituted 4-aza-7,9-dideazaadenosine C-nucleosides.

Aesop Cho, Oliver L Saunders, Thomas Butler, Lijun Zhang, Jie Xu, Jennifer E Vela, Joy Y Feng, Adrian S Ray, Choung U Kim,

A series of 1'-substituted analogs of 4-aza-7,9-dideazaadenosine C-nucleoside were prepared and evaluated for the potential as antiviral agents. These compounds showed a broad range of inhibitory activity against various RNA viruses. In particular, the whole cell potency against HCV when R=CN was attributed to inhibition of HCV NS5B polymerase and ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2012, 22(8):2705-2707]

Cited: 34 times

View full text PDF listing >>



Advertisement

Disclaimer
1.1656 s