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Article ; Online: Defining Pharmacological Targets by Analysis of Virus-Host Protein Interactions.

Llano, Manuel / Peña-Hernandez, Mario A

Advances in protein chemistry and structural biology

2017 Volume 111, Page(s) 223–242

Abstract: Viruses are obligate parasites that depend on cellular factors for replication. Pharmacological inhibition of essential viral proteins, mostly enzymes, is an effective therapeutic alternative in the absence of effective vaccines. However, this strategy ... ...

Abstract	Viruses are obligate parasites that depend on cellular factors for replication. Pharmacological inhibition of essential viral proteins, mostly enzymes, is an effective therapeutic alternative in the absence of effective vaccines. However, this strategy commonly encounters drug resistance mechanisms that allow these pathogens to evade control. Due to the dependency on host factors for viral replication, pharmacological disruption of the host-pathogen protein-protein interactions (PPIs) is an important therapeutic alternative to block viral replication. In this review we discuss salient aspects of PPIs implicated in viral replication and advances in the development of small molecules that inhibit viral replication through antagonism of these interactions.
MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Host Microbial Interactions/drug effects ; Humans ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Viral Proteins/chemistry ; Viral Proteins/drug effects ; Viruses/chemistry ; Viruses/drug effects
Chemical Substances	Antiviral Agents ; Small Molecule Libraries ; Viral Proteins
Keywords	covid19
Language	English
Publishing date	2017-12-18
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	1876-1631 ; 1876-1623
ISSN (online)	1876-1631
ISSN	1876-1623
DOI	10.1016/bs.apcsb.2017.11.001
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Article ; Online: Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection.

Chaguza, Chrispin / Hahn, Anne M / Petrone, Mary E / Zhou, Shuntai / Ferguson, David / Breban, Mallery I / Pham, Kien / Peña-Hernández, Mario A / Castaldi, Christopher / Hill, Verity / Schulz, Wade / Swanstrom, Ronald I / Roberts, Scott C / Grubaugh, Nathan D

Cell reports. Medicine

2023 Volume 4, Issue 2, Page(s) 100943

Abstract: The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity ...

Abstract	The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Persistent Infection ; Genome, Viral ; Genotype
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.100943
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Article: Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses.

Mao, Tianyang / Israelow, Benjamin / Suberi, Alexandra / Zhou, Liqun / Reschke, Melanie / Peña-Hernández, Mario A / Dong, Huiping / Homer, Robert J / Saltzman, W Mark / Iwasaki, Akiko

bioRxiv : the preprint server for biology

2022

Abstract: As the SARS-CoV-2 pandemic enters its third year, vaccines that not only prevent disease, but also prevent transmission are needed to help reduce global disease burden. Currently approved parenteral vaccines induce robust systemic immunity, but poor ... ...

Abstract	As the SARS-CoV-2 pandemic enters its third year, vaccines that not only prevent disease, but also prevent transmission are needed to help reduce global disease burden. Currently approved parenteral vaccines induce robust systemic immunity, but poor immunity at the respiratory mucosa. Here we describe the development of a novel vaccine strategy, Prime and Spike, based on unadjuvanted intranasal spike boosting that leverages existing immunity generated by primary vaccination to elicit mucosal immune memory within the respiratory tract. We show that Prime and Spike induces robust T resident memory cells, B resident memory cells and IgA at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, Prime and Spike enables induction of cross-reactive immunity against sarbecoviruses without invoking original antigenic sin. One-sentence summary: Broad sarbecovirus protective mucosal immunity is generated by unadjuvanted intranasal spike boost in preclinical model.
Language	English
Publishing date	2022-01-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.01.24.477597
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Article ; Online: Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses.

Mao, Tianyang / Israelow, Benjamin / Peña-Hernández, Mario A / Suberi, Alexandra / Zhou, Liqun / Luyten, Sophia / Reschke, Melanie / Dong, Huiping / Homer, Robert J / Saltzman, W Mark / Iwasaki, Akiko

Science (New York, N.Y.)

2022 Volume 378, Issue 6622, Page(s) eabo2523

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for vaccines that not only prevent disease but also prevent transmission. Parenteral vaccines induce robust systemic immunity but poor immunity at the ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for vaccines that not only prevent disease but also prevent transmission. Parenteral vaccines induce robust systemic immunity but poor immunity at the respiratory mucosa. We developed a vaccine strategy that we call "prime and spike," which leverages existing immunity generated by primary vaccination (prime) to elicit mucosal immune memory within the respiratory tract by using unadjuvanted intranasal spike boosters (spike). We show that prime and spike induces robust resident memory B and T cell responses, induces immunoglobulin A at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, prime and spike enables the induction of cross-reactive immunity against sarbecoviruses.
MeSH term(s)	Animals ; Mice ; Administration, Intranasal ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19/transmission ; Immunity, Mucosal ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Vaccination/methods ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; Immunoglobulin A ; Memory B Cells/immunology ; Memory T Cells/immunology ; Immunologic Memory
Chemical Substances	Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; COVID-19 Vaccines ; Immunoglobulin A
Language	English
Publishing date	2022-11-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abo2523
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Article ; Online: LRRC15 inhibits SARS-CoV-2 cellular entry in trans.

Song, Jaewon / Chow, Ryan D / Peña-Hernández, Mario A / Zhang, Li / Loeb, Skylar A / So, Eui-Young / Liang, Olin D / Ren, Ping / Chen, Sidi / Wilen, Craig B / Lee, Sanghyun

PLoS biology

2022 Volume 20, Issue 10, Page(s) e3001805

Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry ... ...

Abstract	Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory attachment factor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single-cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not coexpressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory attachment factor for SARS-CoV-2 that regulates viral entry in trans.
MeSH term(s)	Humans ; Angiotensin-Converting Enzyme 2/genetics ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism ; COVID-19/genetics ; Protein Binding ; Membrane Proteins/genetics ; Membrane Proteins/metabolism
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; LRRC15 protein, human ; Membrane Proteins
Language	English
Publishing date	2022-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001805
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Article: Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection.

medRxiv : the preprint server for health sciences

2022

Abstract: The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic ... ...

Abstract	The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral loads. During the infection, we found an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution led to the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, using unique molecular indexes for accurate intrahost viral sequencing, we tracked the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, ultimately providing opportunity for the emergence of genetically divergent and potentially highly transmissible variants as seen with Delta and Omicron.
Language	English
Publishing date	2022-07-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.06.29.22276868
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Article: Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Grady, Connor B / Bhattacharjee, Bornali / Silva, Julio / Jaycox, Jillian / Lee, Lik Wee / Monteiro, Valter Silva / Sawano, Mitsuaki / Massey, Daisy / Caraballo, César / Gehlhausen, Jeff R / Tabachnikova, Alexandra / Mao, Tianyang / Lucas, Carolina / Peña-Hernandez, Mario A / Xu, Lan / Tzeng, Tiffany J / Takahashi, Takehiro / Herrin, Jeph / Güthe, Diana Berrent /

Akrami, Athena / Assaf, Gina / Davis, Hannah / Harris, Karen / McCorkell, Lisa / Schulz, Wade L / Grffin, Daniel / Wei, Hannah / Ring, Aaron M / Guan, Leying / Cruz, Charles Dela / Iwasaki, Akiko / Krumholz, Harlan M

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in ... ...

Abstract	Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-β and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.11.24300929
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Article ; Online: Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Mao, Tianyang / Kim, Jooyoung / Peña-Hernández, Mario A / Valle, Gabrielee / Moriyama, Miyu / Luyten, Sophia / Ott, Isabel M / Gomez-Calvo, Maria Luisa / Gehlhausen, Jeff R / Baker, Emily / Israelow, Benjamin / Slade, Martin / Sharma, Lokesh / Liu, Wei / Ryu, Changwan / Korde, Asawari / Lee, Chris J / Silva Monteiro, Valter / Lucas, Carolina /

Dong, Huiping / Yang, Yi / Gopinath, Smita / Wilen, Craig B / Palm, Noah / Dela Cruz, Charles S / Iwasaki, Akiko

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

2024 Volume 121, Issue 18, Page(s) e2319566121

Abstract: Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that ... ...

Abstract	Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.
MeSH term(s)	Animals ; Neomycin/pharmacology ; Neomycin/administration & dosage ; Administration, Intranasal ; Mice ; Humans ; Antiviral Agents/pharmacology ; Antiviral Agents/administration & dosage ; SARS-CoV-2/immunology ; SARS-CoV-2/drug effects ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; Respiratory Tract Infections/immunology ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/virology ; Respiratory Tract Infections/prevention & control ; Nasal Mucosa/immunology ; Nasal Mucosa/virology ; Nasal Mucosa/drug effects ; Disease Models, Animal ; COVID-19 Drug Treatment ; Mesocricetus ; Female ; Influenza A virus/drug effects ; Influenza A virus/immunology
Chemical Substances	Neomycin (I16QD7X297) ; Antiviral Agents
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2319566121
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Article ; Online: De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report.

Gandhi, Shiv / Klein, Jonathan / Robertson, Alexander J / Peña-Hernández, Mario A / Lin, Michelle J / Roychoudhury, Pavitra / Lu, Peiwen / Fournier, John / Ferguson, David / Mohamed Bakhash, Shah A K / Catherine Muenker, M / Srivathsan, Ariktha / Wunder, Elsio A / Kerantzas, Nicholas / Wang, Wenshuai / Lindenbach, Brett / Pyle, Anna / Wilen, Craig B / Ogbuagu, Onyema /

Greninger, Alexander L / Iwasaki, Akiko / Schulz, Wade L / Ko, Albert I

Nature communications

2022 Volume 13, Issue 1, Page(s) 1547

Abstract: SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but have not been reported in patients receiving treatment with the antiviral agent. We present a case of an immunocompromised patient with acquired B-cell deficiency who developed ... ...

Abstract	SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but have not been reported in patients receiving treatment with the antiviral agent. We present a case of an immunocompromised patient with acquired B-cell deficiency who developed an indolent, protracted course of SARS-CoV-2 infection. Remdesivir therapy alleviated symptoms and produced a transient virologic response, but her course was complicated by recrudescence of high-grade viral shedding. Whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase, which was not present in pre-treatment specimens. In vitro experiments demonstrated that the mutation conferred a ~6-fold increase in remdesivir IC
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy ; Coronavirus RNA-Dependent RNA Polymerase ; Female ; Humans ; Immunocompromised Host ; Mutation ; SARS-CoV-2/genetics
Chemical Substances	Antibodies, Monoclonal, Humanized ; imdevimab (2Z3DQD2JHM) ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Coronavirus RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; NSP12 protein, SARS-CoV-2 (EC 2.7.7.48) ; casirivimab (J0FI6WE1QN) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2022-03-17
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-29104-y
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Article ; Online: Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection.

Wei, Jin / Patil, Ajinkya / Collings, Clayton K / Alfajaro, Mia Madel / Liang, Yu / Cai, Wesley L / Strine, Madison S / Filler, Renata B / DeWeirdt, Peter C / Hanna, Ruth E / Menasche, Bridget L / Ökten, Arya / Peña-Hernández, Mario A / Klein, Jon / McNamara, Andrew / Rosales, Romel / McGovern, Briana L / Luis Rodriguez, M / García-Sastre, Adolfo /

White, Kris M / Qin, Yiren / Doench, John G / Yan, Qin / Iwasaki, Akiko / Zwaka, Thomas P / Qi, Jun / Kadoch, Cigall / Wilen, Craig B

Nature genetics

2023 Volume 55, Issue 3, Page(s) 471–483

Abstract: Identification of host determinants of coronavirus infection informs mechanisms of viral pathogenesis and can provide new drug targets. Here we demonstrate that mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) chromatin remodeling complexes, ... ...

Abstract	Identification of host determinants of coronavirus infection informs mechanisms of viral pathogenesis and can provide new drug targets. Here we demonstrate that mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) chromatin remodeling complexes, specifically canonical BRG1/BRM-associated factor (cBAF) complexes, promote severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and represent host-directed therapeutic targets. The catalytic activity of SMARCA4 is required for mSWI/SNF-driven chromatin accessibility at the ACE2 locus, ACE2 expression and virus susceptibility. The transcription factors HNF1A/B interact with and recruit mSWI/SNF complexes to ACE2 enhancers, which contain high HNF1A motif density. Notably, small-molecule mSWI/SNF ATPase inhibitors or degraders abrogate angiotensin-converting enzyme 2 (ACE2) expression and confer resistance to SARS-CoV-2 variants and a remdesivir-resistant virus in three cell lines and three primary human cell types, including airway epithelial cells, by up to 5 logs. These data highlight the role of mSWI/SNF complex activities in conferring SARS-CoV-2 susceptibility and identify a potential class of broad-acting antivirals to combat emerging coronaviruses and drug-resistant variants.
MeSH term(s)	Humans ; Angiotensin-Converting Enzyme 2/genetics ; Chromatin ; COVID-19/genetics ; DNA Helicases/genetics ; Nuclear Proteins/genetics ; SARS-CoV-2 ; Transcription Factors/genetics
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Chromatin ; DNA Helicases (EC 3.6.4.-) ; Nuclear Proteins ; SMARCA4 protein, human (EC 3.6.1.-) ; Transcription Factors
Language	English
Publishing date	2023-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01307-z
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