Constraining evolution and avoiding drug resistance.

What We Do_Schiffer.png

We combine a variety of experimental and computational techniques to understand the molecular basis of drug resistance and pay attention to the ways that the natural substrate specificity is maintained by the resistant viral variants. Our new paradigm of drug design minimizes chances of resistance.

Why We Do It_Schiffer.png

We've realized that through understanding the molecular mechanism by which the disease process occurs we could develop inhibitors that block the disease in such a way that the likelihood of resistance occurring is greatly reduced. 

How We Do It_Schiffer.png

We combine a variety of experimental and computational techniques to understand the molecular basis of drug resistance. 

Who We Are_Schiffer.png

We are a collaborative team of scientists dedicated to understanding and thwarting drug resistance.


Research Highlights

Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state

Maiti A, Hedger AK, Myint W, Balachandran V, Watts JK, Schiffer CA, Matsuo H. Nat Commun. 2022 

 oi: 10.1038/s41467-022-34752-1. PMID: 36402773; PMCID: PMC9675756.

 

Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance

Shaqra AM, Zvornicanin SN, Huang QYJ, Lockbaum GJ, Knapp M, Tandeske L, Bakan DT, Flynn J, Bolon DNA, Moquin S, Dovala D, Kurt Yilmaz N, Schiffer CA. Nat Commun. 2022 

doi: 10.1038/s41467-022-31210-w. PMID: 35729165; PMCID: PMC9211792.

Quantitative structural analysis of influenza virus by cryo-electron tomography and convolutional neural networks

Qiuyu J. Huang, Kangkang Song, Chen Xu, Daniel N.A. Bolon, Jennifer P. Wang, Robert W. Finberg, Celia A. Schiffer, Mohan Somasundaran. Structure March 2022.
DOI:  10.1016/j.str.2022.02.014

 

Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond

Matthew AN, Leidner F, Lockbaum GJ, Henes M, Zephyr J, Hou S, Rao DN, Timm J, Rusere LN, Ragland DA, Paulsen JL, Prachanronarong K, Soumana DI, Nalivaika EA, Kurt Yilmaz N, Ali A, Schiffer CA. Chem Rev. 2021 
doi: 10.1021/acs.chemrev.0c00648. Epub 2021 Jan 7. PMID: 33410674; PMCID: PMC8126998.
 
 



 

Latest Schiffer Lab news as reported by the UMass Chan Communications Office

Recent Publications

Total: displaying 10 out of 50 results

  • Efficient convergent synthesis of 1,3-diazepinone nucleosides by ring-closing metathesis and direct glycosylation

    Thursday, November 21, 2024
    Author(s): Adam K Hedger,Jonathan Findell,Dinesh S Barak,Celia A Schiffer,Jonathan K Watts,Akbar Ali
    Source: RSC advances
    A new and highly efficient ring-closing metathesis-based strategy was developed for the synthesis of the cyclic urea 1,3-diazepinone, presenting significant improvement upon previous methods. Using a ...

  • Virion-associated influenza hemagglutinin clusters upon sialic acid binding visualized by cryo-electron tomography

    Monday, October 28, 2024
    Author(s): Qiuyu J Huang,Ryan Kim,Kangkang Song,Nikolaus Grigorieff,James B Munro,Celia A Schiffer,Mohan Somasundaran
    Source: bioRxiv : the preprint server for biology
    Influenza viruses are enveloped, negative sense single-stranded RNA viruses covered in a dense layer of glycoproteins. Hemagglutinin (HA) accounts for 80-90% of influenza glycoprotein and plays a role...

  • Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance

    Saturday, September 28, 2024
    Author(s): Vincent N Azzolino,Ala M Shaqra,Akbar Ali,Nese Kurt Yilmaz,Celia A Schiffer
    Source: Viruses
    Enterovirus-D68 (EV68) has emerged as a global health concern over the last decade with severe symptomatic infections resulting in long-lasting neurological deficits and death. Unfortunately, there ar...

  • FcRn-enhancing mutations lead to increased and prolonged levels of the HIV CCR5-blocking monoclonal antibody leronlimab in the fetuses and newborns of pregnant rhesus macaques

    Thursday, September 26, 2024
    Author(s): Joanna Zikos,Gabriela M Webb,Helen L Wu,Jason S Reed,Jennifer Watanabe,Jodie L Usachenko,Ala M Shaqra,Celia A Schiffer,Koen K A Van Rompay,Jonah B Sacha,Diogo M Magnani
    Source: mAbs
    Prenatal administration of monoclonal antibodies (mAbs) is a strategy that could be exploited to prevent viral infections during pregnancy and early life. To reach protective levels in fetuses, mAbs m...

  • Increasing intracellular dNTP levels improves prime editing efficiency

    Wednesday, September 25, 2024
    Author(s): Pengpeng Liu,Karthikeyan Ponnienselvan,Thomas Nyalile,Sarah Oikemus,Anya T Joynt,Sukanya Iyer,Karen Kelly,Dongsheng Guo,Pyae P Kyawe,Emma Vanderleeden,Sambra D Redick,Lei Huang,Zexiang Chen,Jeong Min ...
    Source: Nature biotechnology
    In primary cell types, intracellular deoxynucleotide triphosphate (dNTP) levels are tightly regulated in a cell cycle-dependent manner. We report that prime editing efficiency is increased by mutation...

  • Next generation APOBEC3 inhibitors: Optimally designed for potency and nuclease stability

    Monday, September 16, 2024
    Author(s): Adam K Hedger,Wazo Myint,Jeong Min Lee,Diego Suchenski-Loustaunau,Vanivilasini Balachandran,Ala M Shaqra,Nese Kurt-Yilmaz,Jonathan K Watts,Hiroshi Matsuo,Celia A Schiffer
    Source: bioRxiv : the preprint server for biology
    APOBEC3 (or A3) enzymes have emerged as potential therapeutic targets due to their role in introducing heterogeneity in viruses and cancer, often leading to drug resistance. Inhibiting these enzymes h...

  • Enabling equitable and affordable access to novel therapeutics for pandemic preparedness and response via creative intellectual property agreements

    Monday, August 26, 2024
    Author(s): Ed J Griffen,Pascale Boulet,ASAP Discovery Center,COVID Moonshot
    Source: Wellcome open research
    The COVID-19 pandemic demonstrated that the current purely market-driven approaches to drug discovery and development alone are insufficient to drive equitable access to new therapies either in prepar...

  • Contributions of Hyperactive Mutations in Mpro from SARS-CoV-2 to Drug Resistance

    Tuesday, March 12, 2024
    Author(s): Julia M Flynn,Sarah N Zvornicanin,Tenzin Tsepal,Ala M Shaqra,Nese Kurt Yilmaz,Weiping Jia,Stephanie Moquin,Dustin Dovala,Celia A Schiffer,Daniel N A Bolon
    Source: ACS infectious diseases
    The appearance and spread of mutations that cause drug resistance in rapidly evolving diseases, including infections by the SARS-CoV-2 virus, are major concerns for human health. Many drugs target enz...

  • Direct delivery of stabilized Cas-embedded base editors achieves efficient and accurate editing of clinically relevant targets

    Monday, February 19, 2024
    Author(s): Jeong Min Lee,Jing Zeng,Pengpeng Liu,My Anh Nguyen,Diego Suchenski Loustaunau,Daniel E Bauer,Nese Kurt Yilmaz,Scot A Wolfe,Celia A Schiffer
    Source: bioRxiv : the preprint server for biology
    Over the last 5 years, cytosine base editors (CBEs) have emerged as a promising therapeutic tool for specific editing of single nucleotide variants and disrupting specific genes associated with diseas...

  • Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

    Thursday, November 09, 2023
    Author(s): Melissa L Boby,Daren Fearon,Matteo Ferla,Mihajlo Filep,Lizbé Koekemoer,Matthew C Robinson,COVID Moonshot Consortium‡,John D Chodera,Alpha A Lee,Nir London,Annette von Delft,Frank von Delft,Hagit Achdo...
    Source: Science (New York, N.Y.)
    We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2...

  • Addressing the dNTP bottleneck restricting prime editing activity

    Tuesday, October 31, 2023
    Author(s): Karthikeyan Ponnienselvan,Pengpeng Liu,Thomas Nyalile,Sarah Oikemus,Anya T Joynt,Karen Kelly,Dongsheng Guo,Zexiang Chen,Jeong Min Lee,Celia A Schiffer,Charles P Emerson,Nathan D Lawson,Jonathan K Watt...
    Source: bioRxiv : the preprint server for biology
    Prime editing efficiency is modest in cells that are quiescent or slowly proliferating where intracellular dNTP levels are tightly regulated. MMLV-reverse transcriptase - the prime editor polymerase s...

  • FruitFire: a luciferase based on a fruit fly metabolic enzyme

    Monday, July 10, 2023
    Author(s): Spencer T Adams,Jacqueto Zephyr,Markus F Bohn,Celia A Schiffer,Stephen C Miller
    Source: bioRxiv : the preprint server for biology
    Firefly luciferase is homologous to fatty acyl-CoA synthetases from insects that are not bioluminescent. Here, we determined the crystal structure of the fruit fly fatty acyl-CoA synthetase CG6178 to ...

  • Systematic Analyses of the Resistance Potential of Drugs Targeting SARS-CoV-2 Main Protease

    Friday, June 30, 2023
    Author(s): Julia M Flynn,Qiu Yu J Huang,Sarah N Zvornicanin,Gila Schneider-Nachum,Ala M Shaqra,Nese Kurt Yilmaz,Stephanie A Moquin,Dustin Dovala,Celia A Schiffer,Daniel N A Bolon
    Source: ACS infectious diseases
    Drugs that target the main protease (M^(pro)) of SARS-CoV-2 are effective therapeutics that have entered clinical use. Wide-scale use of these drugs will apply selection pressure for the evolution of ...

  • HIV-1 protease inhibitors with a P1 phosphonate modification maintain potency against drug-resistant variants by increased interactions with flap residues

    Saturday, May 27, 2023
    Author(s): Gordon J Lockbaum,Linah N Rusere,Mina Henes,Klajdi Kosovrasti,Desaboini Nageswara Rao,Ean Spielvogel,Sook-Kyung Lee,Ellen A Nalivaika,Ronald Swanstrom,Nese Kurt Yilmaz,Celia A Schiffer,Akbar Ali
    Source: European journal of medicinal chemistry
    Protease inhibitors are the most potent antivirals against HIV-1, but they still lose efficacy against resistant variants. Improving the resistance profile is key to developing more robust inhibitors,...

  • Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses

    Thursday, March 30, 2023
    Author(s): Sarah N Zvornicanin,Ala M Shaqra,Qiuyu J Huang,Elizabeth Ornelas,Mallika Moghe,Mark Knapp,Stephanie Moquin,Dustin Dovala,Celia A Schiffer,Nese Kurt Yilmaz
    Source: Viruses
    With the spread of SARS-CoV-2 throughout the globe causing the COVID-19 pandemic, the threat of zoonotic transmissions of coronaviruses (CoV) has become even more evident. As human infections have bee...

  • Selection of HIV-1 for resistance to fifth-generation protease inhibitors reveals two independent pathways to high-level resistance

    Wednesday, March 15, 2023
    Author(s): Ean Spielvogel,Sook-Kyung Lee,Shuntai Zhou,Gordon J Lockbaum,Mina Henes,Amy Sondgeroth,Klajdi Kosovrasti,Ellen A Nalivaika,Akbar Ali,Nese Kurt Yilmaz,Celia A Schiffer,Ronald Swanstrom
    Source: eLife
    Darunavir (DRV) is exceptional among potent HIV-1 protease inhibitors (PIs) in high drug concentrations that are achieved in vivo. Little is known about the de novo resistance pathway for DRV. We sele...

  • Non-canonical pattern recognition of a pathogen-derived metabolite by a nuclear hormone receptor identifies virulent bacteria in C. elegans

    Wednesday, February 22, 2023
    Author(s): Nicholas D Peterson,Samantha Y Tse,Qiuyu Judy Huang,Khursheed A Wani,Celia A Schiffer,Read Pukkila-Worley
    Source: Immunity
    Distinguishing infectious pathogens from harmless microorganisms is essential for animal health. The mechanisms used to identify infectious microbes are not fully understood, particularly in metazoan ...

  • Allosteric quinoxaline-based inhibitors of the flavivirus NS2B/NS3 protease

    Tuesday, November 29, 2022
    Author(s): Jacqueto Zephyr,Desaboini Nageswara Rao,Colby Johnson,Ala M Shaqra,Ellen A Nalivaika,Aria Jordan,Nese Kurt Yilmaz,Akbar Ali,Celia A Schiffer
    Source: Bioorganic chemistry
    Viruses from the Flavivirus genus infect millions of people worldwide and cause severe diseases, including recent epidemics of dengue virus (DENV), and Zika virus (ZIKV). There is currently no antivir...

  • Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state

    Saturday, November 19, 2022
    Author(s): Atanu Maiti,Adam K Hedger,Wazo Myint,Vanivilasini Balachandran,Jonathan K Watts,Celia A Schiffer,Hiroshi Matsuo
    Source: Nature communications
    APOBEC3 proteins (A3s) are enzymes that catalyze the deamination of cytidine to uridine in single-stranded DNA (ssDNA) substrates, thus playing a key role in innate antiviral immunity. However, the AP...

  • Dual Inhibitors of Main Protease (MPro) and Cathepsin L as Potent Antivirals against SARS-CoV2

    Thursday, November 10, 2022
    Author(s): Santanu Mondal,Yongzhi Chen,Gordon J Lockbaum,Sudeshna Sen,Sauradip Chaudhuri,Archie C Reyes,Jeong Min Lee,Arshia N Kaur,Nadia Sultana,Michael D Cameron,Scott A Shaffer,Celia A Schiffer,Katherine A Fi...
    Source: Journal of the American Chemical Society
    Given the current impact of SARS-CoV2 and COVID-19 on human health and the global economy, the development of direct acting antivirals is of paramount importance. Main protease (M^(Pro)), a cysteine p...

  • Mucosal nanobody IgA as inhalable and affordable prophylactic and therapeutic treatment against SARS-CoV-2 and emerging variants

    Thursday, September 29, 2022
    Author(s): Qi Li,Fiachra Humphries,Roxie C Girardin,Aaron Wallace,Monir Ejemel,Alla Amcheslavsky,Conor T McMahon,Zachary A Schiller,Zepei Ma,John Cruz,Alan P Dupuis,Anne F Payne,Arooma Maryam,Nese Kurt Yilmaz,Ka...
    Source: Frontiers in immunology
    Anti-COVID antibody therapeutics have been developed but not widely used due to their high cost and escape of neutralization from the emerging variants. Here, we describe the development of VHH-IgA1.1...

  • Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance

    Tuesday, June 21, 2022
    Author(s): Ala M Shaqra,Sarah N Zvornicanin,Qiu Yu J Huang,Gordon J Lockbaum,Mark Knapp,Laura Tandeske,David T Bakan,Julia Flynn,Daniel N A Bolon,Stephanie Moquin,Dustin Dovala,Nese Kurt Yilmaz,Celia A Schiffer
    Source: Nature communications
    Coronaviruses can evolve and spread rapidly to cause severe disease morbidity and mortality, as exemplified by SARS-CoV-2 variants of the COVID-19 pandemic. Although currently available vaccines remai...

  • Comprehensive fitness landscape of SARS-CoV-2 Mpro reveals insights into viral resistance mechanisms

    Monday, June 20, 2022
    Author(s): Julia M Flynn,Neha Samant,Gily Schneider-Nachum,David T Barkan,Nese Kurt Yilmaz,Celia A Schiffer,Stephanie A Moquin,Dustin Dovala,Daniel N A Bolon
    Source: eLife
    With the continual evolution of new strains of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that are more virulent, transmissible, and able to evade current vaccines, there is an urgen...

  • HIV-1 VIF and human APOBEC3G interaction directly observed through molecular specific labeling using a new dual promotor vector

    Friday, May 13, 2022
    Author(s): Wazo Myint,Celia A Schiffer,Hiroshi Matsuo
    Source: Journal of magnetic resonance (San Diego, Calif. : 1997)
    Over the last few decades, protein NMR isotope labeling methods using E. coli based expression have revolutionized the information accessible from biomolecular NMR experiments. Selective labeling of a...

  • Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness

    Friday, March 18, 2022
    Author(s): Gily Schneider-Nachum,Julia Flynn,David Mavor,Celia A Schiffer,Daniel N A Bolon
    Source: Virus evolution
    Investigating the relationships between protein function and fitness provides keys for understanding biochemical mechanisms that underly evolution. Mutations with partial fitness defects can delineate...

  • Quantitative structural analysis of influenza virus by cryo-electron tomography and convolutional neural networks

    Tuesday, March 15, 2022
    Author(s): Qiuyu J Huang,Kangkang Song,Chen Xu,Daniel N A Bolon,Jennifer P Wang,Robert W Finberg,Celia A Schiffer,Mohan Somasundaran
    Source: Structure (London, England : 1993)
    Influenza viruses pose severe public health threats globally. Influenza viruses are extensively pleomorphic, in shape, size, and organization of viral proteins. Analysis of influenza morphology and ul...

  • Call for Papers: Drug Resistance in Infectious Diseases and Beyond

    Wednesday, March 09, 2022
    Author(s): Celia A Schiffer,Daria J Hazuda
    Source: ACS infectious diseases
    No abstract

  • Deciphering the Molecular Mechanism of HCV Protease Inhibitor Fluorination as a General Approach to Avoid Drug Resistance

    Sunday, February 20, 2022
    Author(s): Jacqueto Zephyr,Desaboini Nageswara Rao,Sang V Vo,Mina Henes,Klajdi Kosovrasti,Ashley N Matthew,Adam K Hedger,Jennifer Timm,Elise T Chan,Akbar Ali,Nese Kurt Yilmaz,Celia A Schiffer
    Source: Journal of molecular biology
    Third generation Hepatitis C virus (HCV) NS3/4A protease inhibitors (PIs), glecaprevir and voxilaprevir, are highly effective across genotypes and against many resistant variants. Unlike earlier PIs, ...

  • Identification of a Permissive Secondary Mutation That Restores the Enzymatic Activity of Oseltamivir Resistance Mutation H275Y

    Wednesday, January 19, 2022
    Author(s): Li Jiang,Neha Samant,Ping Liu,Mohan Somasundaran,Jeffrey D Jensen,Wayne A Marasco,Timothy F Kowalik,Celia A Schiffer,Robert W Finberg,Jennifer P Wang,Daniel N A Bolon
    Source: Journal of virology
    Many oseltamivir resistance mutations exhibit fitness defects in the absence of drug pressure that hinders their propagation in hosts. Secondary permissive mutations can rescue fitness defects and fac...

  • Viral proteases: Structure, mechanism and inhibition

    Saturday, December 04, 2021
    Author(s): Jacqueto Zephyr,Nese Kurt Yilmaz,Celia A Schiffer
    Source: The Enzymes
    Viral proteases are diverse in structure, oligomeric state, catalytic mechanism, and substrate specificity. This chapter focuses on proteases from viruses that are relevant to human health: human immu...

  • Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode

    Friday, September 10, 2021
    Author(s): Gordon J Lockbaum,Mina Henes,Jeong Min Lee,Jennifer Timm,Ellen A Nalivaika,Paul R Thompson,Nese Kurt Yilmaz,Celia A Schiffer
    Source: Biochemistry
    Rupintrivir targets the 3C cysteine proteases of the picornaviridae family, which includes rhinoviruses and enteroviruses that cause a range of human diseases. Despite being a pan-3C protease inhibito...

  • Discovery of Quinoxaline-Based P1-P3 Macrocyclic NS3/4A Protease Inhibitors with Potent Activity against Drug-Resistant Hepatitis C Virus Variants

    Wednesday, August 18, 2021
    Author(s): Desaboini Nageswara Rao,Jacqueto Zephyr,Mina Henes,Elise T Chan,Ashley N Matthew,Adam K Hedger,Hasahn L Conway,Mohsan Saeed,Alicia Newton,Christos J Petropoulos,Wei Huang,Nese Kurt Yilmaz,Celia A Schi...
    Source: Journal of medicinal chemistry
    The three pan-genotypic HCV NS3/4A protease inhibitors (PIs) currently in clinical use-grazoprevir, glecaprevir, and voxilaprevir-are quinoxaline-based P2-P4 macrocycles and thus exhibit similar resis...

  • Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations

    Saturday, July 31, 2021
    Author(s): Frauke Muecksch,Yiska Weisblum,Christopher O Barnes,Fabian Schmidt,Dennis Schaefer-Babajew,Zijun Wang,Julio C C Lorenzi,Andrew I Flyak,Andrew T DeLaitsch,Kathryn E Huey-Tubman,Shurong Hou,Celia A Schi...
    Source: Immunity
    Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute res...

  • Structural basis of substrate specificity in human cytidine deaminase family APOBEC3s

    Friday, June 25, 2021
    Author(s): Shurong Hou,Jeong Min Lee,Wazo Myint,Hiroshi Matsuo,Nese Kurt Yilmaz,Celia A Schiffer
    Source: The Journal of biological chemistry
    The human cytidine deaminase family of APOBEC3s (A3s) plays critical roles in both innate immunity and the development of cancers. A3s comprise seven functionally overlapping but distinct members that...

  • Deciphering Antifungal Drug Resistance in Pneumocystis jirovecii DHFR with Molecular Dynamics and Machine Learning

    Thursday, June 17, 2021
    Author(s): Florian Leidner,Nese Kurt Yilmaz,Celia A Schiffer
    Source: Journal of chemical information and modeling
    Drug resistance impacts the effectiveness of many new therapeutics. Mutations in the therapeutic target confer resistance; however, deciphering which mutations, often remote from the enzyme active sit...

  • Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit

    Thursday, June 10, 2021
    Author(s): Matthew D Hall,James M Anderson,Annaliesa Anderson,David Baker,Jay Bradner,Kyle R Brimacombe,Elizabeth A Campbell,Kizzmekia S Corbett,Kara Carter,Sara Cherry,Lillian Chiang,Tomas Cihlar,Emmie de Wit,M...
    Source: The Journal of infectious diseases
    The NIH Virtual SARS-CoV-2 Antiviral Summit, held on 6 November 2020, was organized to provide an overview on the status and challenges in developing antiviral therapeutics for coronavirus disease 201...

  • Deciphering Complex Mechanisms of Resistance and Loss of Potency through Coupled Molecular Dynamics and Machine Learning

    Tuesday, March 30, 2021
    Author(s): Florian Leidner,Nese Kurt Yilmaz,Celia A Schiffer
    Source: Journal of chemical theory and computation
    Drug resistance threatens many critical therapeutics through mutations in the drug target. The molecular mechanisms by which combinations of mutations, especially those remote from the active site, al...

  • Development of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies

    Wednesday, March 24, 2021
    Author(s): Frauke Muecksch,Yiska Weisblum,Christopher O Barnes,Fabian Schmidt,Dennis Schaefer-Babajew,Julio C C Lorenzi,Andrew I Flyak,Andrew T DeLaitsch,Kathryn E Huey-Tubman,Shurong Hou,Celia A Schiffer,Christ...
    Source: bioRxiv : the preprint server for biology
    Antibodies elicited in response to infection undergo somatic mutation in germinal centers that can result in higher affinity for the cognate antigen. To determine the effects of somatic mutation on th...

  • Introduction: Drug Resistance

    Wednesday, March 24, 2021
    Author(s): Nese Kurt Yilmaz,Celia A Schiffer
    Source: Chemical reviews
    No abstract

  • Inhibiting HTLV-1 Protease: A Viable Antiviral Target

    Tuesday, February 23, 2021
    Author(s): Gordon J Lockbaum,Mina Henes,Nathaniel Talledge,Linah N Rusere,Klajdi Kosovrasti,Ellen A Nalivaika,Mohan Somasundaran,Akbar Ali,Louis M Mansky,Nese Kurt Yilmaz,Celia A Schiffer
    Source: ACS chemical biology
    Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that can cause severe paralytic neurologic disease and immune disorders as well as cancer. An estimated 20 million people worldwide are ...

  • NAD(H) phosphates mediate tetramer assembly of human C-terminal binding protein (CtBP)

    Monday, February 01, 2021
    Author(s): Jeffry C Nichols,Celia A Schiffer,William E Royer
    Source: The Journal of biological chemistry
    C-terminal binding proteins (CtBPs) are cotranscriptional factors that play key roles in cell fate. We have previously shown that NAD(H) promotes the assembly of similar tetramers from either human Ct...

  • Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Non-Covalent Inhibitor ML188

    Thursday, January 28, 2021
    Author(s): Gordon J Lockbaum,Archie C Reyes,Jeong Min Lee,Ronak Tilvawala,Ellen A Nalivaika,Akbar Ali,Nese Kurt Yilmaz,Paul R Thompson,Celia A Schiffer
    Source: Viruses
    Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 i...

  • Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

    Tuesday, January 26, 2021
    Author(s): Wayne D Harshbarger,Derrick Deming,Gordon J Lockbaum,Nattapol Attatippaholkun,Maliwan Kamkaew,Shurong Hou,Mohan Somasundaran,Jennifer P Wang,Robert W Finberg,Quan Karen Zhu,Celia A Schiffer,Wayne A Ma...
    Source: Nature communications
    Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we re...

  • Interactions of APOBEC3s with DNA and RNA

    Sunday, January 24, 2021
    Author(s): Atanu Maiti,Shurong Hou,Celia A Schiffer,Hiroshi Matsuo
    Source: Current opinion in structural biology
    APOBEC3 enzymes are key enzymes in our innate immune system regulating antiviral response in HIV and unfortunately adding diversity in cancer as they deaminate cytosine. Seven unique single and double...

  • Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond

    Thursday, January 07, 2021
    Author(s): Ashley N Matthew,Florian Leidner,Gordon J Lockbaum,Mina Henes,Jacqueto Zephyr,Shurong Hou,Desaboini Nageswara Rao,Jennifer Timm,Linah N Rusere,Debra A Ragland,Janet L Paulsen,Kristina Prachanronarong,...
    Source: Chemical reviews
    Drug resistance is prevalent across many diseases, rendering therapies ineffective with severe financial and health consequences. Rather than accepting resistance after the fact, proactive strategies ...

  • Cryo-EM structure of CtBP2 confirms tetrameric architecture

    Wednesday, December 02, 2020
    Author(s): Anne M Jecrois,M Michael Dcona,Xiaoyan Deng,Dipankar Bandyopadhyay,Steven R Grossman,Celia A Schiffer,William E Royer
    Source: Structure (London, England : 1993)
    C-terminal binding proteins 1 and 2 (CtBP1 and CtBP2) are transcriptional regulators that activate or repress many genes involved in cellular development, apoptosis, and metastasis. NADH-dependent CtB...

  • Crystal Structure of a Soluble APOBEC3G Variant Suggests ssDNA to Bind in a Channel that Extends between the Two Domains

    Sunday, October 25, 2020
    Author(s): Atanu Maiti,Wazo Myint,Krista A Delviks-Frankenberry,Shurong Hou,Tapan Kanai,Vanivilasini Balachandran,Christina Sierra Rodriguez,Rashmi Tripathi,Nese Kurt Yilmaz,Vinay K Pathak,Celia A Schiffer,Hiros...
    Source: Journal of molecular biology
    APOBEC3G (A3G) is a single-stranded DNA (ssDNA) cytosine deaminase that can restrict HIV-1 infection by mutating the viral genome. A3G consists of a non-catalytic N-terminal domain (NTD) and a catalyt...

  • A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction

    Sunday, August 23, 2020
    Author(s): Monir Ejemel,Qi Li,Shurong Hou,Zachary A Schiller,Julia A Tree,Aaron Wallace,Alla Amcheslavsky,Nese Kurt Yilmaz,Karen R Buttigieg,Michael J Elmore,Kerry Godwin,Naomi Coombes,Jacqueline R Toomey,Ryan S...
    Source: Nature communications
    COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal im...

  • Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes

    Wednesday, July 29, 2020
    Author(s): Erica P Cai,Yuki Ishikawa,Wei Zhang,Nayara C Leite,Jian Li,Shurong Hou,Badr Kiaf,Jennifer Hollister-Lock,Nese Kurt Yilmaz,Celia A Schiffer,Douglas A Melton,Stephan Kissler,Peng Yi
    Source: Nature metabolism
    Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic beta cells. Pluripotent stem cells can now be differentiated into beta cells, thus raising the prospect of a cell replacemen...

  • Structural Analysis of Potent Hybrid HIV-1 Protease Inhibitors Containing Bis-tetrahydrofuran in a Pseudosymmetric Dipeptide Isostere

    Friday, July 17, 2020
    Author(s): Linah N Rusere,Gordon J Lockbaum,Mina Henes,Sook-Kyung Lee,Ean Spielvogel,Desaboini Nageswara Rao,Klajdi Kosovrasti,Ellen A Nalivaika,Ronald Swanstrom,Nese Kurt Yilmaz,Celia A Schiffer,Akbar Ali
    Source: Journal of medicinal chemistry
    The design, synthesis, and X-ray structural analysis of hybrid HIV-1 protease inhibitors (PIs) containing bis-tetrahydrofuran (bis-THF) in a pseudo-C(2)-symmetric dipeptide isostere are described. A s...
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Molecular illustrations on this webpage were generated by Leonora Martínez-Núñez, PhD.