Nicholas A. Kovacs

Centers for Disease Control and Prevention

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Loren Dean Williams

Georgia Institute of Technology

Anton S. Petrov

Georgia Institute of Technology

Natalie J. Thornburg

Centers for Disease Control and Prevention

Rebecca Kondor

National Center for Immunization and Respiratory Diseases

Norman Hassell

Centers for Disease Control and Prevention

Kristine A. Lacek

Centers for Disease Control and Prevention

Reina Chau

Centers for Disease Control and Prevention

Benjamin L. Rambo‐Martin

Centers for Disease Control and Prevention

Clinton R. Paden

Centers for Disease Control and Prevention

David E. Wentworth

Centers for Disease Control and Prevention

Cooperative Institutions

Centers for Disease Control and Prevention

101

National Center for Immunization and Respiratory Diseases

Georgia Institute of Technology

National Institutes of Health

National Center for Emerging and Zoonotic Infectious Diseases

Vanderbilt University Medical Center

AID Atlanta

Oak Ridge Associated Universities

Battelle

The University of Texas Medical Branch at Galveston

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Circular Permutation Obscures Universality of a Ribosomal Protein

Journal of Molecular Evolution (2018)

Nicholas A. Kovacs Petar I. Penev Amitej Venapally Anton S. Petrov Loren Dean Williams

Ribosomal protein

10.1007/s00239-018-9869-1

Cite

Citations (9)

Yeast rRNA Expansion Segments: Folding and Function

Journal of Molecular Biology (2016)

Lizzette M. Gómez Ramos Johanna M. Smeekens Nicholas A. Kovacs Jessica C. Bowman Roger M. Wartell

Folding (DSP implementation)

10.1016/j.jmb.2016.08.008

Cite

Citations (23)

Eukaryotic Ribosomal Expansion Segments as Antimicrobial Targets

Biochemistry (2017)

Lizzette M. Gómez Ramos Natalya N. Degtyareva Nicholas A. Kovacs Stefany Y. Holguin Liuwei Jiang

Diversity in eukaryotic rRNA structure and function offers possibilities of therapeutic targets. Unlike ribosomes of prokaryotes, eukaryotic ribosomes contain species-specific rRNA expansion segments (ESs) with idiosyncratic structures and functions that are essential and specific to some organisms. Here we investigate expansion segment 7 (ES7), one of the largest and most variable expansions of the eukaryotic ribosome. We hypothesize that ES7 of the pathogenic fungi Candida albicans (ES7CA) could be a prototypic drug target. We show that isolated ES7CA folds reversibly to a native-like state. We developed a fluorescence displacement assay using an RNA binding fluorescent probe, F-neo. F-neo binds tightly to ES7CA with a Kd of 2.5 × 10-9 M but binds weakly to ES7 of humans (ES7HS) with a Kd estimated to be greater than 7 μM. The fluorescence displacement assay was used to investigate the affinities of a library of peptidic aminosugar conjugates (PAs) for ES7CA. For conjugates with highest affinities for ES7CA (NeoRH, NeoFH, and NeoYH), the lowest dose needed to induce mortality in C. albicans (minimum inhibitory concentration, MIC) was determined. PAs with the lowest MIC values were tested for cytotoxicity in HEK293T cells. Molecules with high affinity for ES7CA in vitro induce mortality in C. albicans but not in HEK293T cells. The results are consistent with the hypothesis that ESs represent useful targets for chemotherapeutics directed against eukaryotic pathogens.

Affinities

10.1021/acs.biochem.7b00703

Cite

Citations (13)

History of the ribosome and the origin of translation

Proceedings of the National Academy of Sciences (2015)

Anton S. Petrov Burak Gulen Ashlyn Norris Nicholas A. Kovacs Chad R. Bernier

We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA. Functions of expansion segments in the ancestral ribosome are assigned by correspondence with their functions in the extant ribosome. The model explains the evolution of the large ribosomal subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. Two additional phases exclusive to eukaryotes led to tentacle-like rRNA expansions. In this model, ribosomal proteinization was a driving force for the broad adoption of proteins in other biological processes. The exit tunnel was clearly a central theme of all phases of ribosomal evolution and was continuously extended and rigidified. In the primitive noncoding ribosome, proto-mRNA and the small ribosomal subunit acted as cofactors, positioning the activated ends of tRNAs within the peptidyl transferase center. This association linked the evolution of the large and small ribosomal subunits, proto-mRNA, and tRNA.

10.1073/pnas.1509761112

Cite

Citations (264)

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves

Vaccines (2024)

Han Di Elizabeth A. Pusch Joyce Jones Nicholas A. Kovacs Norman Hassell

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

spike protein

10.3390/vaccines12050505

Cite

Citations (3)

Data Mining the Structure of the Ribosome to Unravel the History of Proteins

Nicholas A. Kovacs

Source

Cite

Citations (0)

Evolution of the ribosome at atomic resolution

Proceedings of the National Academy of Sciences (2014)

Anton S. Petrov Chad R. Bernier Chiaolong Hsiao Ashlyn Norris Nicholas A. Kovacs

Significance Ribosomes exist in every cell and are responsible for translation from mRNA to protein. The structure of the ribosomal common core is highly conserved in all living species, while the outer regions of the ribosome are variable. Ribosomal RNA of eukaryotes contains expansion segments accreted onto the surface of the core, which is nearly identical in structure to that in prokaryotic ribosomes. Comparing eukaryotic and prokaryotic ribosomes allows us to identify 3D insertion fingerprints of the expansion segments. Similar fingerprints allow us to analyze the common core and detect ancestral expansion segments within it. We construct a molecular model of ribosomal evolution starting from primordial biological systems near the dawn of life, culminating with relatively recent changes specific to metazoans.

Eukaryotic Ribosome

Ribosomal protein

5.8S ribosomal RNA

10.1073/pnas.1407205111

Cite

Citations (204)

Frozen in Time: The History of Proteins

Molecular Biology and Evolution (2017)

Nicholas A. Kovacs Anton S. Petrov Kathryn A. Lanier Loren Dean Williams

The ribosome is imprinted with a detailed molecular chronology of the origins and early evolution of proteins. Here we show that when arranged by evolutionary phase of ribosomal evolution, ribosomal protein (rProtein) segments reveal an atomic level history of protein folding. The data support a model in which aboriginal oligomers evolved into globular proteins in a hierarchical step-wise process. Complexity of assembly and folding of polypeptide increased incrementally in concert with expansion of rRNA. (i) Short random coil proto-peptides bound to rRNA, and (ii) lengthened over time and coalesced into β-β secondary elements. These secondary elements (iii) accreted and collapsed, primarily into β-domains. Domains (iv) accumulated and gained complex super-secondary structures composed of mixtures of α-helices and β-strands. Early protein evolution was guided and accelerated by interactions with rRNA. rRNA and proto-peptide provided mutual protection from chemical degradation and disassembly. rRNA stabilized polypeptide assemblies, which evolved in a stepwise process into globular domains, bypassing the immense space of random unproductive sequences. Coded proteins originated as oligomers and polymers created by the ribosome, on the ribosome and for the ribosome. Synthesis of increasingly longer products was iteratively coupled with lengthening and maturation of the ribosomal exit tunnel. Protein catalysis appears to be a late byproduct of selection for sophisticated and finely controlled assembly.

10.1093/molbev/msx086

Cite

Citations (81)

Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines

Nature Communications (2022)

Li Wang Markus H. Kainulainen Nannan Jiang Han Di Gaston Bonenfant

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.

Pandemic

10.1038/s41467-022-31929-6

Cite

Citations (43)

Differential Mismatch Recognition Specificities of Eukaryotic MutS Homologs, MutSα and MutSβ

Biophysical Journal (2014)

Monika Sharma Alexander V. Predeus Nicholas A. Kovacs Michael Feig

10.1016/j.bpj.2014.04.026

Cite

Citations (22)