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Article ; Online: Cells that survive acute murine SARS-CoV-2 infection are detected nearly exclusively in the respiratory tract.

Pan, Ruangang / Meyerholz, David K / Perlman, Stanley

2023 Volume 133, Issue 22

MeSH term(s)	Animals ; Mice ; COVID-19 ; SARS-CoV-2 ; Respiratory System ; Virus Replication
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI172659
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Article ; Online: Discovery of Nanosota-2, -3, and -4 as super potent and broad-spectrum therapeutic nanobody candidates against COVID-19.

Ye, Gang / Pan, Ruangang / Bu, Fan / Zheng, Jian / Mendoza, Alise / Wen, Wei / Du, Lanying / Spiller, Benjamin / Wadzinski, Brian E / Liu, Bin / Perlman, Stanley / Li, Fang

Journal of virology

2023 Volume 97, Issue 11, Page(s) e0144823

Abstract: Importance: The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single- ... ...

Abstract	Importance: The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single-domain antibodies with therapeutic potentials. We discovered three anti-SARS-CoV-2 nanobodies, named Nanosota-2, -3, and -4, from an immunized alpaca. Nanosota-2 is super potent against prototypic SARS-CoV-2, Nanosota-3 is highly potent against the omicron variant, and Nanosota-4 is effective against both SARS-CoV-1 and SARS-CoV-2. In addition to their super potency and combined broad antiviral spectrum, these nanobodies are cost-effective, can be easily adapted to new viral variants through phage display, and can potentially be administered as inhalers. The Nanosota series are powerful therapeutic candidates to combat circulating SARS-CoV-2 and prepare for possible future coronavirus pandemics.
MeSH term(s)	Humans ; Antibodies, Neutralizing ; Antibodies, Viral/therapeutic use ; COVID-19/therapy ; Pandemics ; SARS-CoV-2 ; Single-Domain Antibodies/pharmacology ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Single-Domain Antibodies ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01448-23
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Article ; Online: N7-Methylation of the Coronavirus RNA Cap Is Required for Maximal Virulence by Preventing Innate Immune Recognition.

Pan, Ruangang / Kindler, Eveline / Cao, Liu / Zhou, Yu / Zhang, Zhen / Liu, Qianyun / Ebert, Nadine / Züst, Roland / Sun, Ying / Gorbalenya, Alexander E / Perlman, Stanley / Thiel, Volker / Chen, Yu / Guo, Deyin

mBio

2022 Volume 13, Issue 1, Page(s) e0366221

Abstract: The ongoing coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome CoV 2 (SARS-CoV-2) is associated with substantial morbidity and mortality. Understanding the immunological and pathological ... ...

Abstract	The ongoing coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome CoV 2 (SARS-CoV-2) is associated with substantial morbidity and mortality. Understanding the immunological and pathological processes of coronavirus diseases is crucial for the rational design of effective vaccines and therapies for COVID-19. Previous studies showed that 2'-O-methylation of the viral RNA cap structure is required to prevent the recognition of viral RNAs by intracellular innate sensors. Here, we demonstrate that the guanine N7-methylation of the 5' cap mediated by coronavirus nonstructural protein 14 (nsp14) contributes to viral evasion of the type I interferon (IFN-I)-mediated immune response and pathogenesis in mice. A Y414A substitution in nsp14 of the coronavirus mouse hepatitis virus (MHV) significantly decreased N7-methyltransferase activity and reduced guanine N7-methylation of the 5' cap
MeSH term(s)	Humans ; Mice ; Animals ; Methylation ; Virulence ; RNA Caps/metabolism ; COVID-19 ; SARS-CoV-2/genetics ; Immunity, Innate ; Virus Replication ; Interferon Type I/metabolism ; Methyltransferases/metabolism ; Murine hepatitis virus/genetics ; Guanine ; RNA, Viral/genetics ; Viral Nonstructural Proteins/genetics
Chemical Substances	RNA Caps ; Interferon Type I ; Methyltransferases (EC 2.1.1.-) ; Guanine (5Z93L87A1R) ; RNA, Viral ; Viral Nonstructural Proteins
Language	English
Publishing date	2022-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03662-21
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Eicosanoid signalling blockade protects middle-aged mice from severe COVID-19.

Nature

2022 Volume 605, Issue 7908, Page(s) 146–151

Abstract: Coronavirus disease 2019 (COVID-19) is especially severe in aged ... ...

Abstract	Coronavirus disease 2019 (COVID-19) is especially severe in aged populations
MeSH term(s)	Animals ; COVID-19 ; Eicosanoids ; Leukocytes, Mononuclear ; Mice ; Organic Chemicals ; Oxazoles ; Piperazines ; Polyesters ; Prostaglandins ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Sulfonamides
Chemical Substances	Eicosanoids ; Organic Chemicals ; Oxazoles ; Piperazines ; Polyesters ; Prostaglandins ; Spike Glycoprotein, Coronavirus ; Sulfonamides ; spike protein, SARS-CoV-2 ; asapiprant (B2LW71CRGL)
Language	English
Publishing date	2022-03-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-04630-3
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

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Article ; Online: Oligodendrocytes that survive acute coronavirus infection induce prolonged inflammatory responses in the CNS.

Pan, Ruangang / Zhang, Qinran / Anthony, Scott M / Zhou, Yu / Zou, Xiufen / Cassell, Martin / Perlman, Stanley

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

2020 Volume 117, Issue 27, Page(s) 15902–15910

Abstract: Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Here, using a lineage-tracking system, we show that some cells, ... ...

Abstract	Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Here, using a lineage-tracking system, we show that some cells, primarily oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs), survive the acute MHV infection, are associated with regions of demyelination, and persist in the central nervous system (CNS) for at least 150 d. These surviving OLs express major histocompatibility complex (MHC) class I and other genes associated with an inflammatory response. Notably, the extent of inflammatory cell infiltration was variable, dependent on anatomic location within the CNS, and without obvious correlation with numbers of surviving cells. We detected more demyelination in regions with larger numbers of T cells and microglia/macrophages compared to those with fewer infiltrating cells. Conversely, in regions with less inflammation, these previously infected OLs more rapidly extended processes, consistent with normal myelinating function. Together, these results show that OLs are inducers as well as targets of the host immune response and demonstrate how a CNS infection, even after resolution, can induce prolonged inflammatory changes with CNS region-dependent impairment in remyelination.
MeSH term(s)	Animals ; Central Nervous System/immunology ; Coronavirus Infections/complications ; Coronavirus Infections/immunology ; Demyelinating Diseases/etiology ; Histocompatibility Antigens Class I/metabolism ; Luminescent Proteins ; Male ; Mice ; Murine hepatitis virus ; Oligodendroglia/immunology ; Oligodendroglia/metabolism ; Red Fluorescent Protein
Chemical Substances	Histocompatibility Antigens Class I ; Luminescent Proteins
Keywords	covid19
Language	English
Publishing date	2020-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2003432117
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Zs.A 1148: Show issues

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Article ; Online: Live attenuated coronavirus vaccines deficient in N7-Methyltransferase activity induce both humoral and cellular immune responses in mice.

Zhang, Zhen / Liu, Qianyun / Sun, Ying / Li, Jiali / Liu, Jiejie / Pan, Ruangang / Cao, Liu / Chen, Xianying / Li, Yingjian / Zhang, Yuzhen / Xu, Ke / Guo, Deyin / Zhou, Li / Lan, Ke / Chen, Yu

Emerging microbes & infections

2021 Volume 10, Issue 1, Page(s) 1626–1637

Abstract: Coronaviruses (CoVs) can infect a variety of hosts, including humans, livestock and companion animals, and pose a serious threat to human health and the economy. The current COVID-19 pandemic, which is caused by severe acute respiratory syndrome ... ...

Abstract	Coronaviruses (CoVs) can infect a variety of hosts, including humans, livestock and companion animals, and pose a serious threat to human health and the economy. The current COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed millions of people. Unfortunately, effective treatments for CoVs infection are still lacking, suggesting the importance of coronavirus vaccines. Our previous work showed that CoV nonstuctural protein 14 (nsp14) functions as (guanine-N7)-methyltransferase (N7-MTase), which is involved in RNA cap formation. Moreover, we found that N7-MTase is well conserved among different CoVs and is a universal target for developing antivirals against CoVs. Here, we show that N7-MTase of CoVs can be an ideal target for designing live attenuated vaccines. Using murine hepatitis virus strain A59 (MHV-A59), a representative and well-studied model of coronaviruses, we constructed N7-MTase-deficient recombinant MHV D330A and Y414A. These two mutants are highly attenuated in mice and exhibit similar replication efficiency to the wild-type (WT) virus in the cell culture. Furthermore, a single dose immunization of D330A or Y414A can induce long-term humoral immune responses and robust CD4
MeSH term(s)	Animals ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; Cytokines/biosynthesis ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Immunogenicity, Vaccine ; Interferon Type I/biosynthesis ; Male ; Mice ; Mutation ; SARS-CoV-2/immunology ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/immunology
Chemical Substances	COVID-19 Vaccines ; Cytokines ; Interferon Type I ; Vaccines, Attenuated ; Viral Nonstructural Proteins
Language	English
Publishing date	2021-08-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2021.1964385
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Characterizing and controlling the inflammatory network during influenza A virus infection.

Jin, Suoqin / Li, Yuanyuan / Pan, Ruangang / Zou, Xiufen

Scientific reports

2014 Volume 4, Page(s) 3799

Abstract: To gain insights into the pathogenesis of influenza A virus (IAV) infections, this study focused on characterizing the inflammatory network and identifying key proteins by combining high-throughput data and computational techniques. We constructed the ... ...

Abstract	To gain insights into the pathogenesis of influenza A virus (IAV) infections, this study focused on characterizing the inflammatory network and identifying key proteins by combining high-throughput data and computational techniques. We constructed the cell-specific normal and inflammatory networks for H5N1 and H1N1 infections through integrating high-throughput data. We demonstrated that better discrimination between normal and inflammatory networks by network entropy than by other topological metrics. Moreover, we identified different dynamical interactions among TLR2, IL-1β, IL10 and NFκB between normal and inflammatory networks using optimization algorithm. In particular, good robustness and multistability of inflammatory sub-networks were discovered. Furthermore, we identified a complex, TNFSF10/HDAC4/HDAC5, which may play important roles in controlling inflammation, and demonstrated that changes in network entropy of this complex negatively correlated to those of three proteins: TNFα, NFκB and COX-2. These findings provide significant hypotheses for further exploring the molecular mechanisms of infectious diseases and developing control strategies.
MeSH term(s)	Entropy ; Gene Regulatory Networks ; Humans ; Inflammation/complications ; Inflammation/genetics ; Inflammation/pathology ; Inflammation/virology ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Influenza A Virus, H5N1 Subtype/pathogenicity ; Influenza, Human/complications ; Influenza, Human/genetics ; Influenza, Human/pathology ; Influenza, Human/virology ; Models, Theoretical
Keywords	covid19
Language	English
Publishing date	2014-01-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep03799
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Oligodendrocytes that survive acute coronavirus infection induce prolonged inflammatory responses in the CNS

Pan, Ruangang / Zhang, Qinran / Anthony, Scott M / Zhou, Yu / Zou, Xiufen / Cassell, Martin / Perlman, Stanley

Proc Natl Acad Sci U S A

Abstract	Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Here, using a lineage-tracking system, we show that some cells, primarily oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs), survive the acute MHV infection, are associated with regions of demyelination, and persist in the central nervous system (CNS) for at least 150 d. These surviving OLs express major histocompatibility complex (MHC) class I and other genes associated with an inflammatory response. Notably, the extent of inflammatory cell infiltration was variable, dependent on anatomic location within the CNS, and without obvious correlation with numbers of surviving cells. We detected more demyelination in regions with larger numbers of T cells and microglia/macrophages compared to those with fewer infiltrating cells. Conversely, in regions with less inflammation, these previously infected OLs more rapidly extended processes, consistent with normal myelinating function. Together, these results show that OLs are inducers as well as targets of the host immune response and demonstrate how a CNS infection, even after resolution, can induce prolonged inflammatory changes with CNS region-dependent impairment in remyelination.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #611002
Database	COVID19

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Article: Pathogens and epidemiologic feature of severe fever with thrombocytopenia syndrome in Hubei province, China

Zhan, Jianbo / Cheng, Jing / Hu, Bing / Li, Jing / Pan, Ruangang / Yang, Zhaohui / Zou, Wenjing / Zhan, Faxian / Guo, Deyin

Virus research. 2017 Mar. 15, v. 232

2017

Abstract: To evaluate the aetiological agents and epidemiologic features of severe fever with thrombocytopenia syndrome (SFTS) in Hubei province, China, sera from patients were collected from January to December 2011. All cases occurred from April to December, and ...

Abstract	To evaluate the aetiological agents and epidemiologic features of severe fever with thrombocytopenia syndrome (SFTS) in Hubei province, China, sera from patients were collected from January to December 2011. All cases occurred from April to December, and the epidemic peaked from May to August. The ages of patients ranged from 10 to 86 years (median=55years), and the incidence of SFTS increased with age. The female:male ratio of cases was 1.008:1, and 54.6% (77/141) and 1.4% (2/141) of the cases were confirmed by qPCR to be SFTSV and Hantavirus (HV) infection, respectively. No case of simultaneous infection with two or more pathogens was found. The research in this paper showed that some suspected SFTS cases are confused with HV infection due to similar symptoms. The analysis showed that the distribution of SFTSV has a marked regional aggregation in Hubei province.
Keywords	quantitative polymerase chain reaction ; fever ; Orthohantavirus ; thrombocytopenia ; patients ; pathogens ; China ; covid19
Language	English
Dates of publication	2017-0315
Size	p. 63-68.
Publishing place	Elsevier B.V.
Document type	Article
Note	2019-12-06
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2017.01.009
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1965: Show issues

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Article ; Online: Pathogens and epidemiologic feature of severe fever with thrombocytopenia syndrome in Hubei province, China.

Zhan, Jianbo / Cheng, Jing / Hu, Bing / Li, Jing / Pan, Ruangang / Yang, Zhaohui / Zou, Wenjing / Zhan, Faxian / Guo, Deyin

Virus research

2017 Volume 232, Page(s) 63–68

Abstract	To evaluate the aetiological agents and epidemiologic features of severe fever with thrombocytopenia syndrome (SFTS) in Hubei province, China, sera from patients were collected from January to December 2011. All cases occurred from April to December, and the epidemic peaked from May to August. The ages of patients ranged from 10 to 86 years (median=55years), and the incidence of SFTS increased with age. The female:male ratio of cases was 1.008:1, and 54.6% (77/141) and 1.4% (2/141) of the cases were confirmed by qPCR to be SFTSV and Hantavirus (HV) infection, respectively. No case of simultaneous infection with two or more pathogens was found. The research in this paper showed that some suspected SFTS cases are confused with HV infection due to similar symptoms. The analysis showed that the distribution of SFTSV has a marked regional aggregation in Hubei province.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bunyaviridae Infections/diagnosis ; Bunyaviridae Infections/epidemiology ; Bunyaviridae Infections/physiopathology ; Bunyaviridae Infections/virology ; Child ; China/epidemiology ; Epidemiological Monitoring ; Female ; Orthohantavirus/genetics ; Orthohantavirus/isolation & purification ; Humans ; Incidence ; Male ; Middle Aged ; Phlebovirus/genetics ; Phlebovirus/isolation & purification ; RNA, Viral/genetics ; RNA, Viral/isolation & purification
Chemical Substances	RNA, Viral
Keywords	covid19
Language	English
Publishing date	2017-01-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2017.01.009
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