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Benjamin Neuman

· ProfessorVerified

Texas A&M University · Microbiology and Immunology

Active 1982–2026

h-index39
Citations14.7k
Papers11244 last 5y
Funding
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About

Benjamin Neuman is a professor at Texas A&M University in the Department of Biology within the College of Arts and Sciences. He joined the department in 2021 and specializes in the study of viruses, focusing on how they work and their origins to better understand and predict new diseases. His research involves examining the structure and assembly of virion proteins, utilizing techniques such as cryo-electron microscopy and mass spectroscopy, with the goal of designing improved vaccines and controlling infections. Neuman's work emphasizes understanding viruses like SARS-CoV-2, including their emergence from other species, as part of pandemic preparedness. His approaches include bioinformatics and molecular biology to discover new RNA viruses and explore antiviral strategies, including the development of antivirals and the use of viruses in phage therapy to control harmful bacteria and support agricultural productivity. His educational background includes a B.S. in Biology from the University of Toledo and a Ph.D. in Animal and Microbial Sciences from the University of Reading (UK), complemented by postdoctoral research at The Scripps Research Institute in Virology.

Research topics

  • Pathology
  • Virology
  • Medicine
  • Biology
  • Immunology
  • Genetics

Selected publications

  • From nicotine to SARS-CoV-2 antivirals with potent in vivo efficacy and a broad anti-coronavirus spectrum

    Nature Communications · 2026-02-14 · 1 citations

    articleOpen access

    Abstract Anecdotal reports about smoking that might prevent SARS-CoV-2 infection inspire the search for nicotine and its pyrolysis products as inhibitors of the SARS-CoV-2 main protease (M Pro ). This effort leads to the discovery of 3-vinylpyridine as an M Pro inhibitor. 3-Vinylpyridine resembles part of nirmatrelvir in binding to M Pro but does not involve a critical interaction with residue E166, whose mutation has led to resistance to nirmatrelvir. Integration of the two molecules, followed by a medicinal chemistry campaign, produces several molecules with better in vitro potency than nirmatrelvir. Two lead molecules, YR-C-136 and SR-B-103, display better pharmacokinetic characteristics than nirmatrelvir in virus-challenged male mice and much better antiviral efficacy in virus-challenged female mice. Both molecules maintain high potency in inhibiting the nirmatrelvir-resistant M Pro (E166V/L50F) variant. They also exhibit a broad and highly potent antiviral spectrum against most pathogenic coronaviruses. With high in vivo potency, both molecules are potentially standalone pan-antivirals for coronaviruses and may serve as countermeasures for future coronavirus outbreaks.

  • From vibrations to function: Spectroscopic detection and quantification of π-π stacking in drug-responsive protein complexes

    Science Advances · 2026-04-08

    articleOpen access

    Aromatic π-π stacking interactions are fundamental to protein architecture, molecular recognition, and drug efficacy, yet directly quantifying them under near-physiological conditions has remained challenging. Here, we use a recently developed spectroscopic platform, thermostable Raman interaction profiling (TRIP), that enables direct, label-free detection and quantification of aromatic π-π interactions in complex protein environments. Using the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) main protease (M pro ) as a biologically and clinically relevant model, we demonstrate that subtle changes in the phenylalanine benzene ring breathing (BRB) mode serve as a precise spectroscopic indicator of π-π stacking strength. This signal is highly responsive to both protein concentration-dependent dimerization and ligand-induced structural changes. M pro forms a catalytically active dimer stabilized by a conserved aromatic triad (phenylalanine-140, histidine-163, and histidine-172), providing an ideal system to interrogate π-stacking at an important protein interface. Potent inhibitors MPI8 and nirmatrelvir produced the strongest BRB spectral shifts, broadening, and intensity changes, consistent with enhanced aromatic stacking and dimer stabilization, whereas halicin and VB-B-145 showed weaker engagement. BRB spectral changes also showed quantitative correlation with dimerization efficiency, published IC 50 (median inhibitory concentration) values, and antiviral efficacy in A549-ACE2 cells. Complementary density functional theory revealed electron density rearrangements and vibrational coupling patterns unique to stacked aromatic residues. This integrated spectroscopic-computational approach enables quantitative probing of π-π stacking in native-like protein environments and positioning TRIP as a generalizable tool for designing drugs targeting aromatic protein-protein interfaces.

  • Nicotine-Inspired, De Novo-Designed SARS-CoV-2 Main Protease Inhibitors Reveal Unique Chemistry for Covalently Conjugating Both Cysteine and Histidine Residues in the Catalytic Dyad

    Journal of the American Chemical Society · 2026-04-14

    articleOpen accessCorresponding

    Anecdotal reports about smokers with low SARS-CoV-2 infection rates prompted a search for nicotine and its pyrolysis products as SARS-CoV-2 main protease (MPro) inhibitors. From this search, 3-vinylpyridine was discovered as a weak binder for the MPro S1 subsite and was used subsequently as a de novo starting point for covalent inhibitor design that quickly yielded a highly potent inhibitor, SR-A-174, with an IC50 value of 60 nM. Representing a novel class of MPro inhibitors, SR-A-174 features an N,N-diaryl-α,α-dichloroacetamide scaffold that facilitated rapid exploration of alternative covalent warheads and various N-substituents, leading to the identification of multiple inhibitors with potent antiviral activity. Eight such MPro inhibitor structures were determined, all demonstrating covalent binding to catalytic Cys145 of MPro. In six determined structures, binding is dominated by the covalent bond plus van der Waals contacts, which contrasts with the extensive hydrogen bond networks formed with peptidomimetic inhibitors such as nirmatrelvir. Strikingly, two N,N-diaryl-α,α-dichloroacetamide inhibitors exhibit an unprecedented dual covalent modification mode of the catalytic dyad, forming bonds to both Cys145 and His41 with a concomitant loss of both chlorides and displacing the inhibitors from the S1 subsite. This dyad-targeting reactivity suggests a novel route for bioconjugation of both cysteine and histidine.

  • Paleoenvironmental reconstruction based on phenotypic variation of the coral Lublinophyllum sp. in the Mississippian Bangor Limestone (Alabama)

    Abstracts with programs - Geological Society of America · 2025-01-01

    article
  • Respiratory Shedding of Infectious SARS-CoV-2 Omicron XBB.1.41.1 Lineage among Captive White-Tailed Deer, Texas, USA

    Emerging infectious diseases · 2025-01-10 · 1 citations

    articleOpen access

    White-tailed deer (Odocoileus virginianus) have high value for research, conservation, agriculture, and recreation and might be key SARS-CoV-2 reservoirs. In November 2023, we sampled 15 female deer in a captive facility in Texas, USA. All deer had neutralizing antibodies to SARS-CoV-2; respiratory swab samples from 11 deer were SARS-CoV-2-positive by quantitative reverse transcription PCR, and 1 deer also had a positive rectal swab sample. Six of the 11 respiratory swab samples yielded infectious virus; replication kinetics of most samples displayed lower growth 24-48 hours postinfection in vitro than Omicron lineages isolated from humans in Texas in the same period. Virus growth was similar between groups by 72 hours, suggesting no strong attenuation of deer-derived virus. All deer viruses clustered in XBB Omicron clade and demonstrated more mutations than expected compared with contemporaneous viruses in humans, suggesting that crossing the species barrier was accompanied by a high substitution rate.

  • Quantum‐enhanced detection of viral cDNA via luminescence resonance energy transfer using upconversion and gold nanoparticles

    Nanophotonics · 2025-03-29 · 4 citations

    articleOpen access

    The COVID-19 pandemic has profoundly impacted global economies and healthcare systems, revealing critical vulnerabilities in both. In response, our study introduces a sensitive and highly specific detection method for cDNA, leveraging Luminescence Resonance Energy Transfer (LRET) between upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs), and achieves a detection limit of 242 fM for SARS-CoV-2 cDNA. This innovative sensing platform utilizes UCNPs conjugated with one primer and AuNPs with another, targeting the 5' and 3' ends of the SARS-CoV-2 cDNA, respectively, enabling precise differentiation of mismatched cDNA sequences and significantly improving detection specificity. Through rigorous experimental analysis, we established a quenching efficiency range from 10.4 % to 73.6 %, with an optimal midpoint of 42 %, thereby demonstrating the superior sensitivity of our method. Our work uses SARS-CoV-2 cDNA as a model system to demonstrate the potential of our LRET-based detection method. This proof-of-concept study highlights the adaptability of our platform for future diagnostic applications. Instrumental validation confirms the synthesis and formation of AuNPs, addressing the need for experimental verification of the preparation of nanomaterial. Our comparative analysis with existing SARS-CoV-2 detection methods revealed that our approach provides a low detection limit and high specificity for target cDNA sequences, underscoring its potential for targeted COVID-19 diagnostics. This study demonstrates the superior sensitivity and adaptability of using UCNPs and AuNPs for cDNA detection, offering significant advances in rapid, accessible diagnostic technologies. Our method, characterized by its low detection limit and high precision, represents a critical step forward in developing next-generation biosensors for managing current and future viral outbreaks. By adjusting primer sequences, this platform can be tailored to detect other pathogens, contributing to the enhancement of global healthcare responsiveness and infectious disease control.

  • Giant RNA genomes: Roles of host, translation elongation, genome architecture, and proteome in nidoviruses

    Proceedings of the National Academy of Sciences · 2025-02-10 · 13 citations

    articleOpen access1st authorCorresponding

    have the largest known RNA genomes of vertebrate and invertebrate viruses with 36.7 and 41.1 kb, respectively. The acquisition of a proofreading exoribonuclease (ExoN) by an ancestral nidovirus enabled crossing of the 20 kb barrier. Other factors constraining genome size variations in nidoviruses remain poorly defined. We assemble 76 genome sequences of invertebrate nidoviruses from >500.000 published transcriptome experiments and triple the number of known nidoviruses with >36 kb genomes, including a 64 kb RNA genome. Many of the identified viral lineages acquired putative enzymatic and other protein domains linked to genome size, host phyla, or virus families. The inserted domains may regulate viral replication and virion formation, or modulate infection otherwise. We classify ExoN-encoding nidoviruses into seven groups and four subgroups, according to canonical and noncanonical modes of viral replicase expression by ribosomes and genomic organization (reModes). The most-represented group employing the canonical reMode comprises invertebrate and vertebrate nidoviruses, including coronaviruses. Six groups with noncanonical reModes include invertebrate nidoviruses with 31-to-64 kb genomes. Among them are viruses with segmented genomes and viruses utilizing dual ribosomal frameshifting that we validate experimentally. Moreover, largest polyprotein length and genome size in nidoviruses show reMode- and host phylum-dependent relationships. We hypothesize that the polyprotein length increase in nidoviruses may be limited by the host-inherent translation fidelity, ultimately setting a nidovirus genome size limit. Thus, expansion of ExoN-encoding RNA virus genomes, the vertebrate/invertebrate host division, the control of viral replicase expression, and translation fidelity are interconnected.

  • Referee report. For: Evidence of mitochondria origin of SARS-CoV-2 double-membrane vesicles: a review. [version 3; peer review: 2 approved, 1 not approved]

    Faculty of 1000 Research Ltd · 2025-01-01

    peer-reviewOpen access1st authorCorresponding
  • Proposed Revision and Early Radiation of Svalbardiinid Brachiopods

    Abstracts with programs - Geological Society of America · 2025-01-01

    article1st authorCorresponding
  • Respiratory shedding of infectious SARS-CoV-2 Omicron XBB.1.41.1 lineage with increased evolutionary rate among captive white-tailed deer

    bioRxiv (Cold Spring Harbor Laboratory) · 2024-09-25 · 1 citations

    preprintOpen access

    Abstract White-tailed deer ( Odocoileus virginianus ) have high value for research, conservation, agriculture and recreation, and may be important SARS-CoV-2 reservoirs with unknown human health implications. In November 2023, we sampled 15 female deer in a captive facility in central Texas, USA. All individuals had neutralizing antibodies against SARS-CoV-2 and 11 had RT-qPCR-positive respiratory swabs; one also had a positive rectal swab. Six of 11 respiratory swabs yielded infectious virus with replication kinetics of most samples displaying lower growth 24-48 h post infection in vitro when compared to Omicron lineages isolated from humans in Texas in the same period. However, virus growth was similar between groups by 72 h, suggesting no strong attenuation of deer-derived virus. All deer viruses clustered in XBB Omicron clade, with more mutations than expected compared to contemporaneous viruses in humans, suggesting that crossing the species barrier to deer was accompanied by a high substitution rate.

Frequent coauthors

  • Marlan O. Scully

    Texas A&M University

    36 shared
  • Michael J. Buchmeier

    University of California, Irvine

    33 shared
  • Philip Hemmer

    29 shared
  • Navid Rajil

    24 shared
  • Zhenhuan Yi

    Texas A&M University

    23 shared
  • Robert W. Brick

    23 shared
  • Shahriar Esmaeili

    Toyota Research Institute

    23 shared
  • А. М. Желтиков

    22 shared

Education

  • PhD in Animal and Microbial Sciences, School of Animal and Microbial Sciences

    University of Reading

    2001
  • BS Biology

    University of Toledo

    1997
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