About

Luis Schang is a Professor of Chemical Virology at the Baker Institute for Animal Health within the College of Veterinary Medicine at Cornell University. His research focuses on molecular virology, specifically on the interactions between viruses and cells that determine infection outcomes and pathogenicity. He is particularly interested in identifying commonalities among unrelated viruses by discovering small molecules that inhibit their infectivity or replication, which serve as probes to understand viral mechanisms and as potential antivirals. His work has led to the identification of broad-spectrum antiviral compounds with novel targets and mechanisms, including the first antiviral molecules targeting virion envelope lipids. His research encompasses viral entry, egress, and the epigenetic regulation of viral replication and pathogenesis, with a focus on pathogens such as herpes simplex virus, hepatitis C virus, influenza A virus, and emerging viruses like Zika virus. Dr. Schang's background includes a veterinary degree from the National University of Buenos Aires and a Ph.D. from the University of Nebraska. His professional experience spans positions at the University of Alberta, where he was an Assistant, Associate, and then Professor of Biochemistry, with cross-appointments in Microbiology and Immunology, and membership in several research groups and institutes. Since 2016, he has been a tenured Professor of Chemical Virology at Cornell University. His notable contributions include pioneering work on antiviral compounds that interfere with viral fusion and membrane dynamics, leading to patents licensed for commercialization, and investigating natural molecules like EGCG for their ability to inhibit virus attachment. His research also explores chromatin dynamics in viral pathogenesis and mechanisms of virus entry and egress, contributing significantly to the understanding of viral biology and antiviral development.

Research topics

• Political Science
• Sociology
• Law
• Economics
• Demography
• Geography
• Econometrics
• Pathology
• Mathematics
• Statistics
• Virology
• Medicine
• Immunology
• Economic geography
• Biology

Selected publications

• Epigenetic inhibitors of BAF chromatin remodeling complexes activate herpes simplex virus 1 transcription in epithelial and fibroblast cells BAF chromatin remodeling complexes during HSV-1 lytic infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-27 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Herpes simplex virus 1 (HSV-1) is a prevalent DNA virus with a major impact on human health. The HSV-1 genome is assembled into silenced stable chromatin and minimally transcribed during latent infection in neurons or assembled into permissive highly dynamic chromatin and highly transcribed during lytic infection in non-neuronal cells. It is unclear how HSV-1 genomes transition from static to highly dynamic chromatin during reactivation, but epigenetics and chromatin dynamics have been proposed to play an important role. Chromatin remodeling complexes regulate cellular chromatin dynamics and contribute to DNA transcription, replication, and repair. The BAF family of chromatin remodeling complexes includes three ubiquitously expressed complexes (cBAF, PBAF, and GBAF) and cell type-specific complexes, including a neuronal BAF (nBAF). Three subunits shared by all BAF complexes and a unique subunit each from cBAF, PBAF, and GBAF were enriched in herpes nuclear domains (HND), which are the novel nuclear domains formed during lytic infection in which HSV-1 genomes are transcribed, replicated, and packaged, and the ATPase SMARCA4, which is shared by all BAF complexes, bound HSV-1 genomes. Four structurally unrelated small molecule bromodomain inhibitors of BAF complexes modulated the abundance of a subset of HSV-1 transcripts, but not genome copy numbers. The inhibitors did not inhibit the recruitment of BAF subunits to HND, and four commonly acetylated histone residues were depleted from HND. We propose that BAF complexes are recruited to the HND by their known interactions with viral proteins and independently of their bromodomains and act early during HSV-1 infection to inhibit viral transcription. These findings also have major implications to the potential of anticancer therapy targeting epigenetic modifiers inducing reactivation of latent herpes simplex viruses. Author Summary Herpes simplex virus 1 (HSV-1) infects over two-thirds of the world population. HSV-1 establishes latency in neurons, resulting in life-long infection. Although most infections are asymptomatic, reactivation can produce a wide range of clinical manifestations, including cold sores, stromal keratitis, and encephalitis. Available treatments do not prevent reactivation or eliminate latent viral reservoirs, as no viral proteins are expressed during latency. Epigenetic regulation plays a role during the lytic and latent cycles. Lytic HSV-1 chromatin is highly dynamic whereas latent chromatin is stable. Chromatin dynamics are regulated by multiple factors, including the chromatin remodeling complexes. Here we show that the BAF chromatin remodeling complexes regulate HSV-1 transcription during lytic infection in primary fibroblast and transformed epithelial human cells. These complexes that are known to be recruited to the viral genomes by viral proteins counterintuitively downregulate viral transcription before the onset of DNA replication but have no effect on viral DNA replication or later gene transcription. We propose that these factors contribute to the orchestrated cascade of viral gene expression.

  PublisherOA PDFDOI

• Deconstructing natural products to develop synthetic small molecule attachment inhibitors with broad spectrum antiviral activity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-22

  preprintOpen accessSenior authorCorresponding

  ABSTRACT The continuous emergence of new viruses and the number of viruses that are each highly consequential for few people raise a need for broad spectrum antivirals. Most human and emerging viruses first attach to cellular glycosaminoglycans (GAG) or sialylated glycans (SG), a potential target for broad spectrum antivirals. Attachment to the former is through polar interactions between the negatively charged glycans and positively charged domains in virion proteins and typically inhibited by negatively charged polymers. Attachment to the latter is through specific interactions at binding pockets and inhibited by molecules that bind to these pockets. Surprisingly, EGCG inhibits viruses that attach to GAG and SG. However, it does so with widely differing potencies, is not a pharmacologically desirable molecule, and is limited by solubility. We tested whether it was possible to develop small synthetic molecules to inhibit viruses that attach to SG or GAG. We first identified the EGCG moieties responsible for the antiviral activity. The two polyhydroxylated phenyl groups were essential while the central benzopyran linker was not. We thus designed a series of gallate compounds to explore the minimal pharmacophore required for broad-spectrum antiviral activity. By exploring the linkers and number of galloyls, we identified small molecule inhibitors of herpes simplex virus 1, influenza A virus, and the coronaviruses hCoV OC43 and SARS-CoV-2. These compounds have low micromolar to submicromolar potency and no limiting cytotoxicity. These molecules are still not pharmacologically optimized and limited by solubility, but they define a minimal pharmacophore that confers broad spectrum antiviral activity. Importance The SARS-CoV-2 pandemic demonstrated the importance of antivirals in managing emerging viruses. Although vaccines were successfully developed in less than two years, there was resistance to vaccination while infected or sick people were far more willing to take antivirals. It is impossible to develop antivirals specific for unknown viruses, but broad spectrum antivirals could control viral spread until more specific and potent drugs are developed. Human pathogenic and emerging viruses commonly attach to glycans, providing a target for broad spectrum antivirals. However, inhibitors of attachment to glycosaminoglycans do not typically inhibit viruses attaching to sialylated glycans, and vice-versa. We had found that EGCG has the unique property of inhibiting viruses that attach both glycans, with quite different potencies. Here, deconstructed a natural compound, EGCG, to identify the moieties responsible for its antiviral activity to then produce broad spectrum antiviral compounds against established and emerging viruses that attach to either glycan.

  PublisherOA PDFDOI

• Meeting report: 38th international conference on antiviral research in Las Vegas, United States of America, March 17–21, 2025

  Antiviral Research · 2025-07-03

  reviewOpen access
  PublisherOA PDFDOI

• ISAR opinion: Product development partnerships to fund pandemic antiviral research

  Antiviral Research · 2025-04-22

  article1st authorCorresponding
  PublisherDOI

• Product Development Partnerships to Fund Pandemic Antiviral Research

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Epigenetic drugs against human DNA viruses and retroviruses

  Antiviral Research · 2025-06-23

  reviewSenior authorCorresponding
  PublisherDOI

• Meeting report of the 37th International Conference on Antiviral Research in Gold Coast, Australia, May 20–24, 2024, organized by the International Society for Antiviral Research

  Antiviral Research · 2024-11-13 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Erp57 facilitates ZIKV-induced DNA damage via NS2B/NS3 complex formation

  Emerging Microbes & Infections · 2024-10-15 · 8 citations

  articleOpen access

  It is believed that DNA double-strand breaks induced by Zika virus (ZIKV) infection in pregnant women is a main reason of brain damage (e.g. microcephaly, severe brain malformation, and neuropathy) in newborn babies [1,2], but its underlying mechanism is poorly understood. In this study, we report that the depletion of ERp57, a member of the protein disulphide isomerase (PDI) family, leads to the limited production of ZIKV in nerve cells. ERp57 knockout not only suppresses viral induced reactive oxygen species (ROS) mediated host DNA damage, but also decreases apoptosis. Strikingly, DNA damage depends on ERp57-bridged complex formation of viral protein NS2B/NS3. LOC14, an ERp57 inhibitor, restricts ZIKV infection and virus-induced DNA damage. Our work reveals an important role of ERp57 in both ZIKV propagation and virus-induced DNA damage, suggesting a potential target against ZIKV infection.

  PublisherDOI

• Histone H2A variant H2A.B is enriched in transcriptionally active and replicating HSV-1 lytic chromatin

  Journal of Virology · 2024-03-07 · 8 citations

  articleOpen accessSenior author

  Herpes simplex virus 1 (HSV-1) transcription is restricted in latently infected neurons and the genomes are in mostly silenced chromatin, whereas all viral genes are transcribed in lytically infected cells, in which the genomes are dynamically chromatinized. Epigenetic regulation modulates HSV-1 transcription during lytic, latent, and reactivating infections but the precise mechanisms are not fully defined. Nucleosomes are dynamic: they slide, breathe, assemble, and disassemble. We and others have proposed that the most dynamic HSV-1 chromatin is transcriptionally competent, whereas the least dynamic is silenced. However, the mechanisms yielding the unusually dynamic viral chromatin remain unknown. Histone variants affect nucleosome dynamics. The dynamics of H2A, H2A.X, and macroH2A were enhanced in infected cells, whereas those of H2A.B were uniquely decreased. We constructed stably transduced cells expressing tagged histone H2A, H2A.B, macroH2A, or H2B, which assembles the H2A/H2B nucleosome dimers with all H2A variants. All H2A variants, as well as ectopic and endogenous H2B were assembled into HSV-1 chromatin evenly throughout the genome but canonical H2A was relatively depleted whereas H2A.B was enriched, particularly in the most dynamic viral chromatin. When viral transcription and DNA replication were restricted, H2A.B became as depleted from the viral chromatin through the entire genome as H2A. We propose that lytic HSV-1 nucleosomes are enriched in the dynamic variant H2A.B/H2B dimers to promote HSV-1 chromatin dynamics and transcriptional competency and conclude that the dynamics of HSV-1 chromatin are determined in part by the H2A variants. IMPORTANCE: Herpes simplex virus 1 (HSV-1) transcription is epigenetically regulated during latent and lytic infections, and epigenetic inhibitors have been proposed as potential antiviral drugs to modulate latency and reactivation. However, the detailed epigenetic mechanisms of regulation of HSV-1 transcription have not been fully characterized and may differ from those regulating cellular transcription. Whereas lytic HSV-1 chromatin is unusually dynamic, latent silenced HSV-1 chromatin is not. The mechanisms resulting in the unique dynamics of the lytic chromatin remain unknown. Here we identify the enrichment of the highly dynamic histone 2A variant H2A in the most dynamic viral chromatin, which provides a mechanistic understanding of its unique dynamics. Future work to identify the mechanisms of enrichment in H2A.B on the viral chromatin may identify novel druggable epigenetic regulators that modulate HSV-1 latency and reactivation.

  PublisherDOI

• Virology under the Microscope—a Call for Rational Discourse

  mSphere · 2023 · 9 citations

  • Political Science
  • Virology
  • Medicine

  Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

  PublisherDOI

Recent grants

• Chromatin dynamics in the regulation of herpes simplex virus 1 gene expression.

  NIH · $1.9M · 2020–2025

• Ménage à trois - Zika virus, DNA damage responses and microcephaly; is PNKP the molecular link?

  NIH · $432k · 2019–2022

Frequent coauthors

• Dominik Wodarz

  University of California, San Diego

  23 shared

• Nathanael S. Gray

  Dana-Farber Cancer Institute

  21 shared

• Daniel P. Depledge

  Medizinische Hochschule Hannover

  16 shared

• Priscilla A. Schaffer

  Rush University Medical Center

  15 shared

• Natalia L. Komarova

  13 shared

• David Durantel

  Inserm

  12 shared

• Andrew Bantly

  University of Pennsylvania

  11 shared

• MiYao Hu

  University of Alberta

  11 shared

Education

• Postdoctoral Fellow, Microbiology

  University of Pennsylvania

  2000

• Research Associate, Veterinary and Biomedical Sciences

  University of Nebraska-Lincoln

  1996

• PhD, Veterinary and Biomedical Sciences

  University of Nebraska-Lincoln

  1995

• MV, Facultad de Ciencias Veterinarias

  Universidad de Buenos Aires

  1987

Awards & honors

• Joseph J. Garbarino Achievement award, Animal Health Institu…
• New Investigator Award, Canadian Institutes of Health Resear…
• AHFMR Scholar Award, Alberta Heritage Foundation for Medical…
• Burroughs-Welcome Fund Investigator in Pathogenesis of Infec…
• McCalla Professorship, University of Alberta (2007)