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Article ; Online: Seasonality of influenza and other respiratory viruses

Gabriele Neumann / Yoshihiro Kawaoka

EMBO Molecular Medicine, Vol 14, Iss 4, Pp n/a-n/a (2022)

2022

Abstract: In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been recognized that outbreaks of human influenza viruses, respiratory syncytial virus (RSV), and ... ...

Abstract	In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been recognized that outbreaks of human influenza viruses, respiratory syncytial virus (RSV), and human coronaviruses occur in temperate climates during the winter season, whereas low activity is detected during the summer months. Other human respiratory viruses, such as parainfluenza viruses, human metapneumoviruses, and rhinoviruses, show highest activity during the spring or fall season in temperate regions, depending on the virus and subtype. In tropical climates, influenza viruses circulate throughout the year and no distinct seasonal patterns are observed, although virus outbreaks tend to spike during the rainy season. Overall, seasonality is more pronounced with greater distance from the equator, and tends to be less pronounced in regions closer to the equator (Li et al, 2019).
Keywords	Medicine (General) ; R5-920 ; Genetics ; QH426-470
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir

Maki Kiso / Yuri Furusawa / Ryuta Uraki / Masaki Imai / Seiya Yamayoshi / Yoshihiro Kawaoka

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 8

Abstract: Abstract Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many ... ...

Abstract	Abstract Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal antibody therapies, potential SARS-CoV-2 resistance to nirmatrelvir is a major public health concern. Several amino acid substitutions have been identified as being responsible for reduced susceptibility to nirmatrelvir. Among them, we selected L50F/E166V and L50F/E166A/L167F in the 3CLpro because these combinations of substitutions are unlikely to affect virus fitness. We prepared and characterized delta variants possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F. Both mutant viruses showed decreased susceptibility to nirmatrelvir and their growth in VeroE6/TMPRSS2 cells was delayed. Both mutant viruses showed attenuated phenotypes in a male hamster infection model, maintained airborne transmissibility, and were outcompeted by wild-type virus in co-infection experiments in the absence of nirmatrelvir, but less so in the presence of the drug. These results suggest that viruses possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F do not become dominant in nature. However, it is important to closely monitor the emergence of nirmatrelvir-resistant SARS-CoV-2 variants because resistant viruses with additional compensatory mutations could emerge, outcompete the wild-type virus, and become dominant.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Triple combination therapy of favipiravir plus two monoclonal antibodies eradicates influenza virus from nude mice

Maki Kiso / Seiya Yamayoshi / Yoshihiro Kawaoka

Communications Biology, Vol 3, Iss 1, Pp 1-

2020 Volume 7

Abstract: Abstract Prolonged treatment of immunocompromised influenza patients with viral neuraminidase (NA) inhibitors is required, because the immune system of such patients fails to eradicate the viruses. Here, we attempted to eradicate influenza virus from the ...

Abstract	Abstract Prolonged treatment of immunocompromised influenza patients with viral neuraminidase (NA) inhibitors is required, because the immune system of such patients fails to eradicate the viruses. Here, we attempted to eradicate influenza virus from the respiratory organs of nude mice, which is a model of immunocompromised hosts, by using combination therapy of the viral polymerase inhibitor favipiravir and monoclonal antibodies (mAbs) against the receptor-binding site (RBS) and stem of viral hemagglutinin (HA). Although monotherapy or combination therapy of two antivirals (two mAbs or favipiravir plus a mAb) suppressed virus replication, they failed to eradicate viruses from nude mice. In contrast, the triple combination therapy of favipiravir plus anti-Stem and anti-RBS mAbs completely stopped virus replication in nude mice, resulting in virus clearance. Triple combination approaches should be considered for the treatment of human immunocompromised patients with severe influenza.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HER2-mediated enhancement of Ebola virus entry.

Makoto Kuroda / Peter Halfmann / Yoshihiro Kawaoka

PLoS Pathogens, Vol 16, Iss 10, p e

2020 Volume 1008900

Abstract: Multiple cell surface molecules including TAM receptors (TYRO3, AXL, and MERTK), a family of tyrosine kinase receptors, can serve as attachment receptors for Ebola virus (EBOV) entry into cells. The interaction of these receptors with EBOV particles is ... ...

Abstract	Multiple cell surface molecules including TAM receptors (TYRO3, AXL, and MERTK), a family of tyrosine kinase receptors, can serve as attachment receptors for Ebola virus (EBOV) entry into cells. The interaction of these receptors with EBOV particles is believed to trigger the initial internalization events that lead to macropinocytosis. However, the details of how these interactions lead to EBOV internalization have yet to be elucidated. Here, we screened receptor tyrosine kinase (RTK) inhibitors for anti-EBOV activity by using our previously established biologically contained Ebola virus that lacks the VP30 gene (EBOVΔVP30) and identified several RTKs, including human epidermal growth factor receptor 2 (HER2), as potential targets of anti-EBOV inhibitors and as novel host factors that have a role in EBOV infection. Of these identified RTKs, it was only HER2 whose knockdown by siRNAs impaired EBOVΔVP30-induced AKT1 phosphorylation, an event that is required for AKT1 activation and subsequent macropinocytosis. Stable expression of HER2 resulted in constitutive activation of AKT1, resulting in the enhancement of EBOVΔVP30 growth, EBOV GP-mediated entry, and macropinocytosis. Moreover, we found that HER2 interacts with the TAM receptors, and in particular forms a complex with TYRO3 and EBOVΔVP30 particles on the cell surface. Interestingly, HER2 was required for EBOVΔVP30-induced TYRO3 and AKT1 activation, but the other TAM receptors (TYRO3 and MERTK) were not essential for EBOVΔVP30-induced HER2 and AKT1 activation. Our findings demonstrate that HER2 plays an important role in EBOV entry and provide novel insights for the development of therapeutics against the virus.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A broadly protective human monoclonal antibody targeting the sialidase activity of influenza A and B virus neuraminidases

Atsuhiro Yasuhara / Seiya Yamayoshi / Maki Kiso / Yuko Sakai-Tagawa / Moe Okuda / Yoshihiro Kawaoka

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 11

Abstract: Broadly protective antibodies targeting influenza viruses are of interest as potential therapeutics or to inform vaccine development. Here the authors characterize a human mAb (DA03E17) with heterosubtypic binding to neuraminidases from IAVs and IBVs ... ...

Abstract	Broadly protective antibodies targeting influenza viruses are of interest as potential therapeutics or to inform vaccine development. Here the authors characterize a human mAb (DA03E17) with heterosubtypic binding to neuraminidases from IAVs and IBVs that provides broad protection in vitro and in vivo.
Keywords	Science ; Q
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: In SARS-CoV-2 delta variants, Spike-P681R and D950N promote membrane fusion, Spike-P681R enhances spike cleavage, but neither substitution affects pathogenicity in hamstersResearch in context

Yuri Furusawa / Maki Kiso / Shun Iida / Ryuta Uraki / Yuichiro Hirata / Masaki Imai / Tadaki Suzuki / Seiya Yamayoshi / Yoshihiro Kawaoka

EBioMedicine, Vol 91, Iss , Pp 104561- (2023)

2023

Abstract: Summary: Background: The SARS-CoV-2 delta (B.1.617.2 lineage) variant was first identified at the end of 2020 and possessed two unique amino acid substitutions in its spike protein: S-P681R, at the S1/S2 cleavage site, and S-D950N, in the HR1 of the S2 ... ...

Abstract	Summary: Background: The SARS-CoV-2 delta (B.1.617.2 lineage) variant was first identified at the end of 2020 and possessed two unique amino acid substitutions in its spike protein: S-P681R, at the S1/S2 cleavage site, and S-D950N, in the HR1 of the S2 subunit. However, the roles of these substitutions in virus phenotypes have not been fully characterized. Methods: We used reverse genetics to generate Wuhan-D614G viruses with these substitutions and delta viruses lacking these substitutions and explored how these changes affected their viral characteristics in vitro and in vivo. Findings: S-P681R enhanced spike cleavage and membrane fusion, whereas S-D950N slightly promoted membrane fusion. Although S-681R reduced the virus replicative ability especially in VeroE6 cells, neither substitution affected virus replication in Calu-3 cells and hamsters. The pathogenicity of all recombinant viruses tested in hamsters was slightly but not significantly affected. Interpretation: Our observations suggest that the S-P681R and S-D950N substitutions alone do not increase virus pathogenicity, despite of their enhancement of spike cleavage or fusogenicity. Funding: A full list of funding bodies that contributed to this study can be found under Acknowledgments.
Keywords	SARS-CoV-2 ; COVID-19 ; Reverse genetics ; Hamster ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir

Maki Kiso / Seiya Yamayoshi / Shun Iida / Yuri Furusawa / Yuichiro Hirata / Ryuta Uraki / Masaki Imai / Tadaki Suzuki / Yoshihiro Kawaoka

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 8

Abstract: Abstract Ensitrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro or Nsp5), is clinically useful against SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to most monoclonal ... ...

Abstract	Abstract Ensitrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro or Nsp5), is clinically useful against SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to most monoclonal antibody therapies, SARS-CoV-2 resistance to other antivirals including main protease inhibitors such as ensitrelvir is a major public health concern. Here, repeating passages of SARS-CoV-2 in the presence of ensitrelvir revealed that the M49L and E166A substitutions in Nsp5 are responsible for reduced sensitivity to ensitrelvir. Both substitutions reduced in vitro virus growth in the absence of ensitrelvir. The combination of the M49L and E166A substitutions allowed the virus to largely evade the suppressive effect of ensitrelvir in vitro. The virus possessing Nsp5-M49L showed similar pathogenicity to wild-type virus, whereas the virus possessing Nsp5-E166A or Nsp5-M49L/E166A slightly attenuated. Ensitrelvir treatment of hamsters infected with the virus possessing Nsp5-M49L/E166A was ineffective; however, nirmatrelvir or molnupiravir treatment was effective. Therefore, it is important to closely monitor the emergence of ensitrelvir-resistant SARS-CoV-2 variants to guide antiviral treatment selection.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants

Michael J. Moser / Lindsay Hill-Batorski / Richard A. Bowen / Sarah M. Matejka / David Marshall / Yoshihiro Kawaoka / Gabriele Neumann / Pamuk Bilsel

Vaccines, Vol 11, Iss 1063, p

2023 Volume 1063

Abstract: Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from ...

Abstract	Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine candidate, employing our live intranasal M2-deficient single replication (M2SR) influenza vector expressing the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein of the prototype strain, first reported in January 2020. The intranasal vaccination of mice with this dual vaccine elicits both high serum IgG and mucosal IgA titers to RBD. Sera from inoculated mice show that vaccinated mice develop neutralizing SARS-CoV-2 antibody titers against the prototype and Delta virus strains, which are considered to be sufficient to protect against viral infection. Moreover, SARS-CoV-2 M2SR elicited cross-reactive serum and mucosal antibodies to the Omicron BA.4/BA.5 variant. The SARS-CoV-2 M2SR vaccine also maintained strong immune responses to influenza A with high titers of anti H3 serum IgG and hemagglutination inhibition (HAI) antibody titers corresponding to those seen from the control M2SR vector alone. With a proven safety record and robust immunological profile in humans that includes mucosal immunity, the M2SR influenza viral vector expressing key SARS-CoV-2 antigens could provide more efficient protection against influenza and SARS-CoV-2 variants.
Keywords	influenza ; SARS-CoV-2 ; COVID-19 ; vaccine ; intranasal ; mucosal ; Medicine ; R
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Co-infection with SARS-CoV-2 and influenza A virus

Shuhei Azekawa / Ho Namkoong / Keiko Mitamura / Yoshihiro Kawaoka / Fumitake Saito

IDCases, Vol 20, Iss , Pp e00775- (2020)

2020

Abstract: Coronavirus Disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is spreading globally and poses a major public health threat. We reported a case of influenza A virus and SARS-CoV-2 co-infection. As ... ...

Abstract	Coronavirus Disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is spreading globally and poses a major public health threat. We reported a case of influenza A virus and SARS-CoV-2 co-infection. As the number of COVID-19 cases increase, it will be necessary to comprehensively evaluate imaging and other clinical findings as well as consider co-infection with other respiratory viruses.
Keywords	COVID-19 ; SARS-CoV-2 ; Influenza ; Co-infection ; Infectious and parasitic diseases ; RC109-216 ; covid19
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CRISPR-Cas3-based diagnostics for SARS-CoV-2 and influenza virus

Kazuto Yoshimi / Kohei Takeshita / Seiya Yamayoshi / Satomi Shibumura / Yuko Yamauchi / Masaki Yamamoto / Hiroshi Yotsuyanagi / Yoshihiro Kawaoka / Tomoji Mashimo

iScience, Vol 25, Iss 2, Pp 103830- (2022)

2022

Abstract: Summary: CRISPR-based diagnostics (CRISPR-dx), including the Cas12-based DETECTR and Cas13-based SHERLOCK Class 2 CRISPRs, have been used to detect the presence of DNA or RNA from pathogens, such as the 2009 pandemic influenza virus A (IAV) and the 2019 ... ...

Abstract	Summary: CRISPR-based diagnostics (CRISPR-dx), including the Cas12-based DETECTR and Cas13-based SHERLOCK Class 2 CRISPRs, have been used to detect the presence of DNA or RNA from pathogens, such as the 2009 pandemic influenza virus A (IAV) and the 2019 novel coronavirus SARS-CoV-2. Here, we describe the collateral single-stranded DNA cleavage with Class 1 type I CRISPR-Cas3 and highlight its potential for development as a Cas3-mediated rapid (within 40 min), low-cost, instrument-free detection method for SARS-CoV-2. This assay, which we call Cas3-Operated Nucleic Acid detectioN (CONAN), not only detects SARS-CoV-2 in clinical samples, but also offers specific detection of single-base-pair mutations in IAV variants. This tool allows rapid and accurate point-of-care testing for patients with suspected SARS-CoV-2 or drug-resistant IAV infections in hospitals.
Keywords	Diagnostics ; Virology ; Science ; Q
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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