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Article ; Online: Progress and Challenges in the Development of COVID-19 Vaccines and Current Understanding of SARS-CoV-2- Specific Immune Responses.

Kim, Kyun-Do / Hwang, Insu / Ku, Keun Bon / Lee, Sumin / Kim, Seong-Jun / Kim, Chonsaeng

Journal of microbiology and biotechnology

2020 Volume 30, Issue 8, Page(s) 1109–1115

Abstract: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread ...

Abstract	The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.
MeSH term(s)	Adaptive Immunity ; Betacoronavirus/immunology ; COVID-19 ; COVID-19 Vaccines ; Coronavirus Infections/immunology ; Coronavirus Infections/prevention & control ; Drug Development ; Humans ; Immunity, Innate ; Pandemics/prevention & control ; Pneumonia, Viral/immunology ; Pneumonia, Viral/prevention & control ; SARS-CoV-2 ; Viral Vaccines/immunology ; Viral Vaccines/therapeutic use
Chemical Substances	COVID-19 Vaccines ; Viral Vaccines
Keywords	covid19
Language	English
Publishing date	2020-07-06
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2412195-2
ISSN	1738-8872 ; 1017-7825
ISSN (online)	1738-8872
ISSN	1017-7825
DOI	10.4014/jmb.2006.06006
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Article ; Online: A Crucial Role of ACBD3 Required for Coxsackievirus Infection in Animal Model Developed by AAV-Mediated CRISPR Genome Editing Technique.

Shin, Hye Jin / Ku, Keun Bon / Kim, Soojin / Kim, Heon Seok / Kim, Yeon-Soo / Kim, Bum-Tae / Kim, Seong-Jun / Kim, Chonsaeng

Viruses

2021 Volume 13, Issue 2

Abstract: Genetic screens using CRISPR/Cas9 have been exploited to discover host-virus interactions. These screens have identified viral dependencies on host proteins during their life cycle and potential antiviral strategies. The acyl-CoA binding domain ... ...

Abstract	Genetic screens using CRISPR/Cas9 have been exploited to discover host-virus interactions. These screens have identified viral dependencies on host proteins during their life cycle and potential antiviral strategies. The acyl-CoA binding domain containing 3 (ACBD3) was identified as an essential host factor for the Coxsackievirus B3 (CVB3) infection. Other groups have also investigated the role of ACBD3 as a host factor for diverse enteroviruses in cultured cells. However, it has not been tested if ACBD3 is required in the animal model of CVB3 infection. Owing to embryonic lethality, conventional knockout mice were not available for in vivo study. As an alternative approach, we used adeno-associated virus (AAV)-mediated CRISPR genome editing to generate mice that lacked ACBD3 within the pancreas, the major target organ for CVB3. Delivery of sgRNAs using self-complementary (sc) AAV8 efficiently induced a loss-of-function mutation in the pancreas of the Cas9 knock-in mice. Loss of ACBD3 in the pancreas resulted in a 100-fold reduction in the CVB3 titer within the pancreas and a noticeable reduction in viral protein expression. These results indicate a crucial function of ACBD3 in CVB3 infection in vivo. AAV-mediated CRISPR genome editing may be applicable to many in vivo studies on the virus-host interaction and identify a novel target for antiviral therapeutics.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Clustered Regularly Interspaced Short Palindromic Repeats ; Coxsackievirus Infections/genetics ; Coxsackievirus Infections/metabolism ; Coxsackievirus Infections/virology ; Dependovirus/genetics ; Dependovirus/metabolism ; Disease Models, Animal ; Enterovirus B, Human/physiology ; Gene Editing ; Gene Knockout Techniques ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout
Chemical Substances	Acbd3 protein, mouse ; Adaptor Proteins, Signal Transducing ; Membrane Proteins
Language	English
Publishing date	2021-02-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13020237
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Article ; Online: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity.

Shin, Hye Jin / Kim, Chonsaeng / Cho, Sungchan

Viruses

2018 Volume 10, Issue 4

Abstract: Nucleoside analogs have been frequently identified as antiviral agents. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. ... ...

Abstract	Nucleoside analogs have been frequently identified as antiviral agents. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. Nucleoside analogs generally interfere with cellular nucleos(t)ide synthesis pathways, resulting in the depletion or imbalance of (d)NTP pools. Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. The precise crosstalk between these two independent processes remains to be determined. Nonetheless, we summarize the current knowledge of nucleos(t)ide synthesis inhibition-related innate immunity and propose it as a newly emerging antiviral mechanism of nucleoside analogs.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Gene Expression/drug effects ; Humans ; Immunity, Innate/drug effects ; Immunity, Innate/immunology ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/immunology ; Metabolic Networks and Pathways/drug effects ; Nucleosides/antagonists & inhibitors ; Nucleotides/antagonists & inhibitors
Chemical Substances	Antiviral Agents ; Interferon Regulatory Factors ; Nucleosides ; Nucleotides ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R)
Keywords	covid19
Language	English
Publishing date	2018-04-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v10040211
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Article ; Online: Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant.

Lee, Sunhee / Yoon, Gun Young / Lee, Su Jin / Kwon, Young-Chan / Moon, Hyun Woo / Kim, Yu-Jin / Kim, Haesoo / Lee, Wooseong / Jeong, Gi Uk / Kim, Chonsaeng / Kim, Kyun-Do / Kim, Seong-Jun / Ahn, Dae-Gyun

Microbiology spectrum

2022 Volume 10, Issue 5, Page(s) e0237122

Abstract: Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of the COVID-19 pandemic. We investigated the immunological and pathological peculiarity of the SARS-CoV-2 beta variant of concern (VoC) ... ...

Abstract	Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of the COVID-19 pandemic. We investigated the immunological and pathological peculiarity of the SARS-CoV-2 beta variant of concern (VoC) compared to the ancestral strain. Comparative analysis of phenotype and pathology revealed that the beta VoC induces slower disease progression and a prolonged presymptomatic period in the early stages of SARS-CoV-2 infection but ultimately causes sudden death in the late stages of infection in the K18-hACE2 mouse model. The beta VoC induced enhanced activation of CXCL1/2-CXCR2-NLRP3-IL-1β signal cascade accelerating neutrophil recruitment and lung pathology in beta variant-infected mice, as evidenced by multiple analyses of SARS-CoV-2-induced inflammatory cytokines and transcriptomes. CCL2 was one of the most highly secreted cytokines in the early stages of infection. Its blockade reduced virus-induced weight loss and delayed mortality. Our study provides a better understanding of the variant characteristics and need for treatment.
MeSH term(s)	Mice ; Humans ; Animals ; SARS-CoV-2 ; Pandemics ; Interleukin-1beta/genetics ; COVID-19 ; NLR Family, Pyrin Domain-Containing 3 Protein ; Cytokines ; Disease Models, Animal
Chemical Substances	Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; Cytokines
Language	English
Publishing date	2022-08-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02371-22
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Article: Development of a Subtype-Specific Diagnostic System for Influenza Virus H3N2 Using a Novel Virus-Based Systematic Evolution of Ligands by Exponential Enrichment (Viro-SELEX).

Kwon, Junyoung / Narayan, Chandan / Kim, Chonsaeng / Han, Min Jung / Kim, Meehyein / Jang, Sung Key

Journal of biomedical nanotechnology

2019 Volume 15, Issue 7, Page(s) 1609–1621

Abstract: Aptamers are oligonucleotide molecules that bind to specific target molecules generated by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers have high future potential for use in diagnostics and therapeutics as molecular probes ... ...

Abstract	Aptamers are oligonucleotide molecules that bind to specific target molecules generated by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers have high future potential for use in diagnostics and therapeutics as molecular probes that recognize target molecules. To develop aptamers against a target protein using a SELEX process, it is necessary to purify the target protein. Purifying a membrane protein, however, is usually a challenging task. Here, we report a novel approach to developing aptamers against membrane proteins. Surrogate viruses containing target proteins on the surface of an enveloped virus (e.g., baculovirus), instead of purified proteins, were used in a new SELEX process. We designated this new SELEX process as "surrogate virus-based SELEX (viro-SELEX)." Using viro-SELEX, we developed a pair of aptamers that specifically interact with the hemagglutinin protein of influenza subtype H3N2. Using the aptamer pair and a lateral flow assay system, we developed a very sensitive point-of-care diagnostic system for specifically detecting influenza virus subtype H3N2.
MeSH term(s)	Aptamers, Nucleotide ; Humans ; Influenza A Virus, H3N2 Subtype ; Influenza, Human/diagnosis ; Ligands ; SELEX Aptamer Technique
Chemical Substances	Aptamers, Nucleotide ; Ligands
Language	English
Publishing date	2019-05-31
Publishing country	United States
Document type	Journal Article
ISSN	1550-7033
ISSN	1550-7033
DOI	10.1166/jbn.2019.2789
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Article ; Online: Virus-based SELEX (viro-SELEX) allows development of aptamers targeting knotty proteins.

Narayan, Chandan / Kwon, Junyoung / Kim, Chonsaeng / Kim, Seong-Jun / Jang, Sung Key

The Analyst

2019 Volume 145, Issue 4, Page(s) 1473–1482

Abstract: It has been 100 years since the worst flu (Spanish flu) mankind has ever experienced. Rapid, accurate diagnosis and subtyping of flu are still an urgent unmet medical need. By using surrogate virus-based SELEX (viro-SELEX), we report here multiple ... ...

Abstract	It has been 100 years since the worst flu (Spanish flu) mankind has ever experienced. Rapid, accurate diagnosis and subtyping of flu are still an urgent unmet medical need. By using surrogate virus-based SELEX (viro-SELEX), we report here multiple advances incorporated into the field of flu diagnostics: (i) aptamers that can bind to the native virus well even though they cannot bind strongly to a recombinant protein (hemagglutinin); (ii) a couple of aptamers that can target a broad range of strains belonging to the H1N1 subtype and detect only the H1N1 subtype and nothing else; (iii) a highly sensitive lateral flow assay system (limit of detection is 0.08 HAU) using fluorescence-tagged aptamers. The viro-SELEX method of aptamer selection in conjunction with a fluorescent tag on aptamers is a very useful approach to develop highly sensitive, specific, portable, rapid, and quantitative point-of-care testing diagnostic tools for the future.
MeSH term(s)	Animals ; Aptamers, Nucleotide/chemistry ; Aptamers, Nucleotide/metabolism ; Collodion/chemistry ; Gold/chemistry ; Influenza A virus/isolation & purification ; Influenza A virus/metabolism ; Limit of Detection ; Metal Nanoparticles/chemistry ; SELEX Aptamer Technique/methods ; Sf9 Cells ; Spodoptera ; Viral Proteins/analysis ; Viral Proteins/metabolism
Chemical Substances	Aptamers, Nucleotide ; Viral Proteins ; Gold (7440-57-5) ; Collodion (9004-70-0)
Language	English
Publishing date	2019-12-23
Publishing country	England
Document type	Journal Article
ZDB-ID	210747-8
ISSN	1364-5528 ; 0003-2654
ISSN (online)	1364-5528
ISSN	0003-2654
DOI	10.1039/c9an01943j
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Article ; Online: Repurposing Screens of FDA-Approved Drugs Identify 29 Inhibitors of SARS-CoV-2.

Ku, Keun Bon / Shin, Hye Jin / Kim, Hae Soo / Kim, Bum-Tae / Kim, Seong-Jun / Kim, Chonsaeng

Journal of microbiology and biotechnology

2020 Volume 30, Issue 12, Page(s) 1843–1853

Abstract: COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread globally and caused serious social and economic problems. The WHO has declared this outbreak a pandemic. Currently, there are no approved vaccines or antiviral drugs that prevent SARS-CoV-2 ...

Abstract	COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread globally and caused serious social and economic problems. The WHO has declared this outbreak a pandemic. Currently, there are no approved vaccines or antiviral drugs that prevent SARS-CoV-2 infection. Drugs already approved for clinical use would be ideal candidates for rapid development as COVID-19 treatments. In this work, we screened 1,473 FDA-approved drugs to identify inhibitors of SARS-CoV-2 infection using cell-based assays. The antiviral activity of each compound was measured based on the immunofluorescent staining of infected cells using anti-dsRNA antibody. Twenty-nine drugs among those tested showed antiviral activity against SARS-CoV-2. We report this new list of inhibitors to quickly provide basic information for consideration in developing potential therapies.
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/toxicity ; Drug Approval ; Drug Repositioning ; Humans ; SARS-CoV-2/drug effects ; United States ; United States Food and Drug Administration
Chemical Substances	Antiviral Agents
Keywords	covid19
Language	English
Publishing date	2020-11-16
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2412195-2
ISSN	1738-8872 ; 1017-7825
ISSN (online)	1738-8872
ISSN	1017-7825
DOI	10.4014/jmb.2009.09009
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Article: Progress and Challenges in the Development of COVID-19 Vaccines and Current Understanding of SARS-CoV-2- Specific Immune Responses

Kim, Kyun-Do / Hwang, Insu / Ku, Keun Bon / Lee, Sumin / Kim, Seong-Jun / Kim, Chonsaeng

J Microbiol Biotechnol

Abstract	The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #634732
Database	COVID19

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Article: Structure-Based Virtual Screening: Identification of a Novel NS2B-NS3 Protease Inhibitor with Potent Antiviral Activity against Zika and Dengue Viruses.

Shin, Hye Jin / Kim, Mi-Hwa / Lee, Joo-Youn / Hwang, Insu / Yoon, Gun Young / Kim, Hae Soo / Kwon, Young-Chan / Ahn, Dae-Gyun / Kim, Kyun-Do / Kim, Bum-Tae / Kim, Seong-Jun / Kim, Chonsaeng

Microorganisms

2021 Volume 9, Issue 3

Abstract: Zika virus (ZIKV), which is associated with severe diseases in humans, has spread rapidly and globally since its emergence. ZIKV and dengue virus (DENV) are closely related, and antibody-dependent enhancement (ADE) of infection between cocirculating ZIKV ...

Abstract	Zika virus (ZIKV), which is associated with severe diseases in humans, has spread rapidly and globally since its emergence. ZIKV and dengue virus (DENV) are closely related, and antibody-dependent enhancement (ADE) of infection between cocirculating ZIKV and DENV may exacerbate disease. Despite these serious threats, there are currently no approved antiviral drugs against ZIKV and DENV. The NS2B-NS3 viral protease is an attractive antiviral target because it plays a pivotal role in polyprotein cleavage, which is required for viral replication. Thus, we sought to identify novel inhibitors of the NS2B-NS3 protease. To that aim, we performed structure-based virtual screening using 467,000 structurally diverse chemical compounds. Then, a fluorescence-based protease inhibition assay was used to test whether the selected candidates inhibited ZIKV protease activity. Among the 123 candidate inhibitors selected from virtual screening, compound 1 significantly inhibited ZIKV NS2B-NS3 protease activity in vitro. In addition, compound 1 effectively inhibited ZIKV and DENV infection of human cells. Molecular docking analysis suggested that compound 1 binds to the NS2B-NS3 protease of ZIKV and DENV. Thus, compound 1 could be used as a new therapeutic option for the development of more potent antiviral drugs against both ZIKV and DENV, reducing the risks of ADE.
Language	English
Publishing date	2021-03-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9030545
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Article ; Online: Comparison of Plaque Size, Thermal Stability, and Replication Rate among SARS-CoV-2 Variants of Concern.

Jeong, Gi Uk / Yoon, Gun Young / Moon, Hyun Woo / Lee, Wooseong / Hwang, Insu / Kim, Haesoo / Kim, Kyun-Do / Kim, Chonsaeng / Ahn, Dae-Gyun / Kim, Bum-Tae / Kim, Seong-Jun / Kwon, Young-Chan

Viruses

2021 Volume 14, Issue 1

Abstract: SARS-CoV-2, like other RNA viruses, has a propensity for genetic evolution owing to the low fidelity of its viral polymerase. Several recent reports have described a series of novel SARS-CoV-2 variants. Some of these have been identified as variants of ... ...

Abstract	SARS-CoV-2, like other RNA viruses, has a propensity for genetic evolution owing to the low fidelity of its viral polymerase. Several recent reports have described a series of novel SARS-CoV-2 variants. Some of these have been identified as variants of concern (VOCs), including alpha (B.1.1.7, Clade GRY), beta (B.1.351, Clade GH), gamma (P.1, Clade GR), and delta (B.1.617.2, Clade G). VOCs are likely to have some effect on transmissibility, antibody evasion, and changes in therapeutic or vaccine effectiveness. However, the physiological and virological understanding of these variants remains poor. We demonstrated that these four VOCs exhibited differences in plaque size, thermal stability at physiological temperature, and replication rates. The mean plaque size of beta was the largest, followed by those of gamma, delta, and alpha. Thermal stability, evaluated by measuring infectivity and half-life after prolonged incubation at physiological temperature, was correlated with plaque size in all variants except alpha. However, despite its relatively high thermal stability, alpha's small plaque size resulted in lower replication rates and fewer progeny viruses. Our findings may inform further virological studies of SARS-CoV-2 variant characteristics, VOCs, and variants of interest. These studies are important for the effective management of the COVID-19 pandemic.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Humans ; SARS-CoV-2/classification ; SARS-CoV-2/physiology ; Temperature ; Vero Cells ; Viral Plaque Assay ; Virus Replication
Language	English
Publishing date	2021-12-30
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14010055
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