- The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo
-
Kyungseob Noh , Eun Ju Jeong , Timothy An , Jin Soo Shin , Hyejin Kim , Soo Bong Han , Meehyein Kim
-
J. Microbiol. 2022;60(5):550-559. Published online April 18, 2022
-
DOI: https://doi.org/10.1007/s12275-022-1661-7
-
-
1,172
View
-
10
Download
-
6
Web of Science
-
6
Crossref
-
 Abstract
 PDF
-
Adjuvants are substances added to vaccines to enhance antigen-
specific immune responses or to protect antigens from
rapid elimination. As pattern recognition receptors, Toll-like
receptors 7 (TLR7) and 8 (TLR8) activate the innate immune
system by sensing endosomal single-stranded RNA of RNA
viruses. Here, we investigated if a 2,4-diaminoquinazolinebased
TLR7/8 agonist, (S)-3-((2-amino-8-fluoroquinazolin-
4-yl)amino)hexan-1-ol (named compound 31), could be used
as an adjuvant to enhance the serological and mucosal immunity
of an inactivated influenza A virus vaccine. The compound induced
the production of proinflammatory cytokines in macrophages.
In a dose-response analysis, intranasal administration
of 1 μg compound 31 together with an inactivated vaccine
(0.5 μg) to mice not only enhanced virus-specific IgG and
IgA production but also neutralized influenza A virus with
statistical significance. Notably, in a virus-challenge model,
the combination of the vaccine and compound 31 alleviated
viral infection-mediated loss of body weight and increased
survival rates by 40% compared with vaccine only-treated mice.
We suggest that compound 31 is a promising lead compound
for developing mucosal vaccine adjuvants to protect against
respiratory RNA viruses such as influenza viruses and potentially
coronaviruses.
-
Citations
Citations to this article as recorded by  - Synthetic Cathepsin B Sensitive Adjuvant‐Peptide Conjugates to Target Intracellular Toll‐Like Receptors 7 and 8
Marjolein M. E. Isendoorn, Giulia Castello, Nico J. Meeuwenoord, Martijn Verdoes, Jeroen D. C. Codée, Ferry Ossendorp, Dmitri V. Filippov
ChemistryEurope.2026;[Epub] CrossRef - Efflux-Enhanced Imidazoquinolines To Exploit Chemoresistance
Muhammad Haroon, Sharmin Sultana, Seyedeh A. Najibi, Emily T. Wang, Abbey Michaelson, Pranto S. M. Al Muied, Amy E. Nielsen, Rock J. Mancini
ACS Omega.2025; 10(12): 12319. CrossRef - Design, Synthesis, and Biological Evaluation of New 2,6,7-Substituted Purine Derivatives as Toll-like Receptor 7 Agonists for Intranasal Vaccine Adjuvants
Morgan Kim, Kyungseob Noh, Pyeongkeun Kim, Jae Ho Kim, Byeong Wook Choi, Ravi Singh, Jun-Ho Choi, Soo Bong Han, Seong Soon Kim, Eun-Young Lee, Myung Ae Bae, Daeho Shin, Meehyein Kim, Jin Hee Ahn
Journal of Medicinal Chemistry.2024; 67(11): 9389. CrossRef - Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2
Hyeon-Min Cha, Uk-Il Kim, Soo Bin Ahn, Myoung Kyu Lee, Haemi Lee, Hyungtae Bang, Yejin Jang, Seong Soon Kim, Myung Ae Bae, Kyungjin Kim, Meehyein Kim
ACS Infectious Diseases.2023; 9(4): 1033. CrossRef - Identification of broad-spectrum neutralizing antibodies against influenza A virus and evaluation of their prophylactic efficacy in mice
Sumin Son, Soo Bin Ahn, Geonyeong Kim, Yejin Jang, Chunkyu Ko, Meehyein Kim, Sang Jick Kim
Antiviral Research.2023; 213: 105591. CrossRef - Inhibition of KIF20A suppresses the replication of influenza A virus by inhibiting viral entry
Hoyeon Jeon, Younghyun Lim, In-Gu Lee, Dong-In Kim, Keun Pil Kim, So-Hee Hong, Jeongkyu Kim, Youn-Sang Jung, Young-Jin Seo
Journal of Microbiology.2022; 60(11): 1113. CrossRef
- Comparison of anti-influenza virus activity and pharmacokinetics of oseltamivir free base and oseltamivir phosphate
-
Jin Soo Shin , Keun Bon Ku , Yejin Jang , Yi-Seul Yoon , Daeho Shin , Oh Seung Kwon , Yun Young Go , Seong Soon Kim , Myoung Ae Bae , Meehyein Kim
-
J. Microbiol. 2017;55(12):979-983. Published online December 7, 2017
-
DOI: https://doi.org/10.1007/s12275-017-7371-x
-
-
2,004
View
-
3
Download
-
10
Crossref
-
Abstract
PDF
-
Influenza viruses are major human respiratory pathogens that
cause high morbidity and mortality worldwide. Currently,
prophylactic vaccines and therapeutic antiviral agents are used
to prevent and control influenza virus infection. Oseltamivir
free base (OSV-FB), a modified generic antiviral drug of
Tamiflu (oseltamivir phosphate, OSV-P), was launched in
the Republic of Korea last year. Here, we examine the bioequivalence
of these two compounds by assessing their antiviral
efficacy in infected cells and in a mouse model. It was
observed that both antivirals showed comparable efficacy
against 11 different influenza A and B viruses in vitro. Moreover,
in mice infected with influenza A virus (mouse-adapted
A/Puerto Rico/8/34), they showed a dose-dependent therapeutic
activity and alleviated infection-mediated reductions
in body weight, leading to significantly better survival. There
was histopathological disappearance of virus-induced inflammatory
cell infiltration of the lung after oral treatment with
either antiviral agent (at 10 mg/kg). Pharmacokinetic analysis
also exhibited similar plasma concentrations of the active
drug, oseltamivir carboxylate, metabolised from both OSVB
and OSV-P. This is the first report showing bioequivalence
of OSV-FB to its phosphate salt form in the mouse system.
The free base drug has some beneficial points including simple
drug formulation process and reduced risk of undesirable
cation-phosphate precipitation within solution. The long term
stability of OSV-FB requires further monitoring when it is
provided as a national stock in readiness for an influenza
pandemic.
-
Citations
Citations to this article as recorded by - Interaction mechanism of oseltamivir phosphate with bovine serum albumin: multispectroscopic and molecular docking study
Jing Yu, Jian-Ming Liu, Hui-Yi Chen, Wei-Ming Xiong
BMC Chemistry.2024;[Epub] CrossRef - A Lysosome-Targeting hNEU1 Inhibitor Treats Myocardial Infarction: A Potential Therapeutic Breakthrough
Wen Zhou, Wanxiang Yang, Ping Jiang, Shaohua Gou
Journal of Medicinal Chemistry.2024; 67(18): 16899. CrossRef - The possible techniques that used to improve the bioavailablity, pharmacological activity, solubility and permeability of anti-viral drugs: Insight for COVID-19 antiviral drugs
Ghassan Mudher Hashim , Ghaidaa S. Hameed , Dalya Basil Hanna
Al Mustansiriyah Journal of Pharmaceutical Sciences.2023; 23(3): 231. CrossRef - Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics
Ran Chen, Tingting Wang, Jie Song, Daojun Pu, Dan He, Jianjun Li, Jie Yang, Kailing Li, Cailing Zhong, Jingqing Zhang
International Journal of Nanomedicine.2021; Volume 16: 4959. CrossRef - Multistage Extraction of Star Anise and Black Pepper Derivatives for Antibacterial, Antioxidant, and Anticancer Activity
Helin Li, Xiaoyu Wu, Xin Li, Xiaobing Cao, Yanjun Li, Huaru Cao, Yongzhi Men
Frontiers in Chemistry.2021;[Epub] CrossRef - Development of Sustained Release Oseltamivir Phosphate Dry Powder Inhaler: In-Vitro Characterization and In-Vivo Toxicological Studies
Harshal Sahastrabudhe, Prathmesh Kenjale, Varsha Pokharkar
Current Drug Delivery.2020; 17(8): 703. CrossRef - In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus
Yejin Jang, Jin Soo Shin, Joo-Youn Lee, Heegwon Shin, Sang Jick Kim, Meehyein Kim
Viruses.2020; 12(5): 581. CrossRef - A new naphthoquinone analogue and antiviral constituents from the root of Rhinacanthus nasutus
Tran Minh Ngoc, Nguyen Thi Thanh Phuong, Nguyen Minh Khoi, SeonJu Park, Hee Jae Kwak, Nguyen Xuan Nhiem, Bui Thi Thu Trang, Bui Huu Tai, Jae-Hyoung Song, Hyun-Jeong Ko, Seung Hyun Kim
Natural Product Research.2019; 33(3): 360. CrossRef - Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function
Yejin Jang, Jin Soo Shin, Yi-Seul Yoon, Yun Young Go, Hye Won Lee, Oh Seung Kwon, Sehee Park, Man-Seong Park, Meehyein Kim, Jae U. Jung
Journal of Virology.2018;[Epub] CrossRef - The Cranberry Extract Oximacro® Exerts in vitro Virucidal Activity Against Influenza Virus by Interfering With Hemagglutinin
Anna Luganini, Maria E. Terlizzi, Gianluca Catucci, Gianfranco Gilardi, Massimo E. Maffei, Giorgio Gribaudo
Frontiers in Microbiology.2018;[Epub] CrossRef
|
MSK
