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Check out some of Schiffer Lab's most recent publications:

Engineered IgA-Fc fusion protein with bioactive nanobody neutralizes SARS-CoV-2 variants with mucosal delivery potential

January 30, 2026

Author(s): Rachel M Golonka,Lauren E Intravaia,Ala M Shaqra,Qi Li,Yongzhi Chen,Fiachra Humphries,Nese Kurt-Yilmaz,Kate A Fitzgerald,Celia A Schiffer,Yang Wang,Lisa A Cavacini

Source: The Journal of biological chemistry

The COVID-19 pandemic accelerated the development of monoclonal antibodies (mAb) targeting SARS-CoV-2, with IgG1-based mAbs dominating the therapeutic landscape. However, IgA-the predominant immunoglo...
Cooperativity and communication between the active sites of the dimeric SARS-CoV-2 main protease

January 16, 2026

Author(s): Sarah N Zvornicanin,Ala M Shaqra,Julia Flynn,Lauren E Intravaia,Heidi Carias Martinez,Weiping Jia,Devendra Kumar Gupta,Stephanie Moquin,Dustin Dovala,Daniel N Bolon,Brian A Kelch,Celia A Schiffer,Nese...

Source: Science advances

The coronaviral main protease (M^(pro)) has been the subject of various biochemical and structural studies and a drug target against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infect...
Fluorinated HIV-1 protease inhibitors containing chiral hydroxyethylbenzene and indanol as P2' ligands with potent activity against drug-resistant variants

December 25, 2025

Author(s): Jagroop Kaur,Ean Spielvogel,Desaboini Nageswara Rao,Linah N Rusere,Ala M Shaqra,Gordon J Lockbaum,Arooma Maryam,Nese Kurt Yilmaz,Ronald Swanstrom,Celia A Schiffer,Akbar Ali

Source: European journal of medicinal chemistry

HIV-1 protease inhibitors are potent antiretroviral drugs, but their efficacy is often undermined by poor pharmacokinetics and drug resistance. Here, we employed a structure-guided design strategy to ...
Structural Analysis of Inhibitor Binding to the Feline Enteric Coronavirus (FECV) Main Protease

November 27, 2025

Author(s): Arooma Maryam,Stephanie A Moquin,Dustin Dovala,Jagroop Kaur,Nese Kurt Yilmaz,Ala M Shaqra,Celia A Schiffer

Source: Viruses

Coronaviruses include various strains that reside in natural animal reservoirs, with zoonotic transmission posing risks to both domesticated animals and human health. Recent efforts to address coronav...
Subnanometer-resolution Structural Determination of Hemagglutinin from Cryo-electron Tomography of Influenza Viruses

November 24, 2025

Author(s): Qiuyu J Huang,Clint N McDaniel,Alijah A Griffith,Celia A Schiffer,Mohan Somasundaran

Source: Journal of visualized experiments : JoVE

Cryo-electron tomography is a powerful tool to visualize heterogeneous samples, with one major application being structural characterization of pleomorphic viruses. In recent years, subtomogram averag...
Predicting the Impact of Drug Resistance Mutations on Inhibitor Potency with Molecular Dynamics and Machine Learning

October 15, 2025

Author(s): Lauren E Intravaia,Ala M Shaqra,Somayeh Pirhadi,Noa Popko,Nese Kurt Yilmaz,Celia A Schiffer

Source: The journal of physical chemistry. B

Many enzymes are vital drug targets in diseases such as cancer and pathogenic infections; however, mutations can drastically disrupt inhibitor binding to confer resistance. Resistance mutations primar...
Cooperativity and Communication between the Active Sites of the Dimeric SARS-CoV-2 Main Protease

August 06, 2025

Author(s): Sarah N Zvornicanin,Ala M Shaqra,Julia Flynn,Lauren E Intravaia,Heidi Carias Martinez,Weiping Jia,Devendra Kumar Gupta,Stephanie Moquin,Dustin Dovala,Daniel N Bolon,Brian A Kelch,Celia A Schiffer,Nese...

Source: bioRxiv : the preprint server for biology

The coronaviral main protease (M ^(pro) ) is essential for the replication of the virus, and has been the subject of various biochemical, structural and enzymatic studies, as well as a drug target aga...
HIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation

July 02, 2025

Author(s): Katarzyna A Skorupka,Kazuhiro Matsuoka,Bakar Hassan,Rodolfo Ghirlando,Vanivilasini Balachandran,Ting-Hua Chen,Kylie J Walters,Celia A Schiffer,Matthias Wolf,Yasumasa Iwatani,Hiroshi Matsuo

Source: Nature communications

The APOBEC3 family of cytidine deaminases restricts retroviruses like HIV-1 by mutating viral DNA. HIV-1 evades this restriction by producing Vif, which recruits the Cullin-5 (CUL5) E3 ubiquitin ligas...
Virion-associated influenza hemagglutinin clusters upon sialic acid binding visualized by cryoelectron tomography

April 17, 2025

Author(s): Qiuyu J Huang,Ryan Kim,Kangkang Song,Nikolaus Grigorieff,James B Munro,Celia A Schiffer,Mohan Somasundaran

Source: Proceedings of the National Academy of Sciences of the United States of America

Influenza viruses are enveloped, negative-sense single-stranded RNA viruses covered in a dense layer of glycoproteins. Hemagglutinin (HA) accounts for 80 to 90% of influenza glycoprotein and plays a r...
Molecular mechanisms of drug resistance and compensation in SARS-CoV-2 main protease: the interplay between E166 and L50

April 04, 2025

Author(s): Sarah N Zvornicanin,Ala M Shaqra,Julia Flynn,Heidi Carias Martinez,Weiping Jia,Stephanie Moquin,Dustin Dovala,Daniel N Bolon,Nese Kurt Yilmaz,Celia A Schiffer

Source: mBio

The SARS-CoV-2 main protease (M^(pro)) is essential for viral replication and is a primary target for COVID-19 antivirals. Direct-acting antivirals such as nirmatrelvir, the active component of Paxlov...
Next generation APOBEC3 inhibitors: optimally designed for potency and nuclease stability

March 29, 2025

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: Nucleic acids research

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...
Structural Analysis of Inhibitor Binding to Enterovirus-D68 3C Protease

January 25, 2025

Author(s): Vincent N Azzolino,Ala M Shaqra,Akbar Ali,Nese Kurt Yilmaz,Celia A Schiffer

Source: Viruses

Enterovirus-D68 (EV68) continues to present as a global health issue causing respiratory illness and outbreaks associated with long-lasting neurological disease, with no antivirals or specific treatme...
Direct delivery of Cas-embedded cytosine base editors as ribonucleoprotein complexes for efficient and accurate editing of clinically relevant targets

December 16, 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: Nucleic acids research

Recently, cytosine base editors (CBEs) have emerged as a promising therapeutic tool for specific editing of single nucleotide variants and disrupting specific genes associated with disease. Despite th...
Efficient convergent synthesis of 1,3-diazepinone nucleosides by ring-closing metathesis and direct glycosylation

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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...