Article
Microbiology
Hye-Jin Shin, Mi-Hwa Kim, Joo-Youn Lee, Insu Hwang, Gun-Young Yoon, Hae-Soo Kim, Young-Chan Kwon, Dae-Gyun Ahn, Kyun-Do Kim, Bum-Tae Kim, Seong-Jun Kim, Chonsaeng Kim
Summary: The Zika virus and dengue virus are closely related and may exacerbate disease when circulating together. A potential drug has been discovered to effectively inhibit the infection of both viruses, showing promise for the development of more potent antiviral drugs.
Article
Chemistry, Medicinal
Somayeh Behrouz, Nikos Kuehl, Christian D. Klein
Summary: This study reports the design, synthesis, and in-vitro characterization of potent peptidic inhibitors of DENV protease with a sulfonyl moiety as N-terminal cap, creating sulfonamide-peptide hybrids. Some synthesized compounds showed in-vitro target affinities in the nanomolar range, with the most promising derivative achieving a Ki value of 78 nM against DENV-2 protease. The synthesized compounds had no relevant off-target activity or cytotoxicity, and exhibited remarkable metabolic stability against rat liver microsomes and pancreatic enzymes. Overall, the integration of sulfonamide moieties at the N-terminus of peptidic inhibitors proved to be a promising and attractive strategy for further drug development against DENV infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Tadahisa Teramoto
Summary: Enzyme activities for replicating DENV 5' cap positive (+) sense RNA have been shown to reside in NS3 and NS5. However, it remains unknown how these enzymes coordinately synthesize negative (-) sense RNA, from which abundant 5' cap (+) sense RNA is produced. We previously revealed that NS5 dimerization and NS5 methyltransferase(MT)-NS3HEL interaction are important for DENV replication. Here, we found that replication incompetence due to NS3PRO or HEL replacement was compensated by a mutation at HEL or NS2B, respectively, suggesting that the interactions among NS2B, NS3PRO, and HEL are critical for DENV replication.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jack Chun-Chieh Hsu, Maudry Laurent-Rolle, Joanna B. Pawlak, Hongjie Xia, Amit Kunte, Jia Shee Hee, Jaechul Lim, Lawrence D. Harris, James M. Wood, Gary B. Evans, Pei-Yong Shi, Tyler L. Grove, Steven C. Almo, Peter Cresswell
Summary: This study reveals a novel antiviral mechanism in which viperin inhibits both cellular and viral RNA translation by activating a ribosome collision-dependent pathway. The SAM activity and enzymatic product of viperin play crucial roles in translation repression. This research highlights the significance of translational repression in the antiviral response and identifies viperin as a translation regulator in innate immunity.
Article
Biophysics
Wen Hao Kenneth Lee, Wei Liu, Jing-Song Fan, Daiwen Yang
Summary: The study revealed the dynamic equilibrium between closed and open conformations of the NS3 protease-NS2B complex of dengue virus in aqueous solution. The stability of NS2B was found to affect the equilibrium between closed and open conformations, with the proteolytic activity of the complex correlating well with the closed conformation. These findings suggest that the closed-open conformational equilibrium can be utilized to control the replication of dengue virus by both nature and human intervention.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Yali Ci, Bin Yao, Kun Yue, Yang Yang, Caimin Xu, De-feng Li, Cheng-Feng Qin, Lei Shi
Summary: Flaviviruses have been a serious threat to human health for decades, and there is a lack of effective therapeutic drugs. This study developed an assay to identify inhibitors that interfere with viral polyprotein cleavage and block Zika virus and dengue virus replication. Bortezomib was found to be the most potent inhibitor, inducing ubiquitination and aggregation of NS3, which attenuated its protease activity. This study identifies bortezomib as a potential drug for treating Zika virus and dengue virus infection and highlights the role of the ERAD pathway in the inhibition of flaviviruses by bortezomib.
CELL CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Shenyou Nie, Jidong Zhao, Xiaowei Wu, Yuan Yao, Fangrui Wu, Yi-Lun Lin, Xin Li, Alexander R. Kneubehl, Megan B. Vogt, Rebecca Rico-Hesse, Yongcheng Song
Summary: A novel series of compounds have been discovered as potent inhibitors of the Zika virus protease, with the most effective ones also showing inhibitory effects on dengue and West Nile virus. The most potent compounds were able to strongly inhibit Zika virus replication in cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Fadi G. Saqallah, Manal A. Abbas, Habibah A. Wahab
Summary: Dengue virus is a mosquito-borne virus that can cause various complications. A tetravalent vaccine is available for children, and the NS2b/NS3 protease is a key target for antiviral agents. Natural products have shown potential as inhibitors of dengue virus, with some compounds found to inhibit the NS2b/NS3 protease. However, further in vivo and clinical studies are needed.
Article
Biochemistry & Molecular Biology
Amaresh Kumar Mohanty, Muthuvel Suresh Kumar
Summary: Dengue fever is an endemic virus-borne disease that can cause severe ailments. The NS2B-NS3 protease plays a crucial role in viral replication, and mutated NS2B can affect the activation of NS3 protease, potentially leading to the occurrence of dengue fever.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
S. Pant, G. Bhattacharya, N. R. Jena
Summary: This study investigates peptide inhibitors targeting the NS2B-NS3 protease of ZIKV and finds that the YKKR peptide inhibitor forms the most stable complex with the protease and strongly inhibits ZIKV proliferation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Pharmacology & Pharmacy
Tadahisa Teramoto, Kyung H. Choi, Radhakrishnan Padmanabhan
Summary: Flaviviruses, including dengue, West Nile, yellow fever, Japanese encephalitis, and Zika virus, are important human pathogens. These viruses cause a range of diseases, from mild symptoms to severe complications. Dengue infections have dramatically increased in recent decades, causing millions of infections and thousands of deaths each year. Zika virus and West Nile virus also pose significant threats to human health, especially to pregnant women and children.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Thales Kronenberger, Mateus Sa Magalhaes Serafim, Arun Kumar Tonduru, Vinicius Goncalves Maltarollo, Antti Poso
Summary: Dengue is a tropical disease caused by the dengue virus, with an estimated 300 million new cases each year. Due to limited vaccine efficacy and lack of effective antiviral treatment, new drug candidates are urgently needed. Molecular dynamics simulations were conducted to study the conformational changes in the DENV-3 NS3-NS2B complex, revealing multiple druggable subpockets that can be explored in drug discovery efforts.
Article
Pharmacology & Pharmacy
Muhammad Usman Mirza, Ida Alanko, Michiel Vanmeert, Kendall M. Muzzarelli, Outi M. H. Salo-Ahen, Iskandar Abdullah, Iulia A. Kovari, Sandra Claes, Steven De Jonghe, Dominique Schols, Raymond F. Schinazi, Ladislau C. Kovari, John F. Trant, Sarfraz Ahmad, Matheus Froeyen
Summary: This study used a computer-aided structure-based approach to screen a library of compounds against ZIKV NS2B-NS3 protease. Several compounds showed promising activity against the protease, and one compound also exhibited anti-ZIKV activity in whole cells. This research provides a promising starting point for the development of novel compounds against ZIKV.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Lata R. Ganji, Lekha Gandhi, Venkataramana Musturi, Meena A. Kanyalkar
Summary: The study focuses on the threat of deaths or critical health issues caused by Dengue virus infection. A series of compounds targeting the dengue protease NS2B-NS3 was designed and synthesized, with CA2, BZ1, and BS2 showing more potent and efficacious protease inhibition activity compared to the standard quercetin.
MEDICINAL CHEMISTRY RESEARCH
(2021)
Article
Cell Biology
Jose Angel Regla-Nava, Ying-Ting Wang, Camila R. Fontes-Garfias, Yang Liu, Thasneem Syed, Mercylia Susantono, Andrew Gonzalez, Karla M. Viramontes, Shailendra Kumar Verma, Kenneth Kim, Sara Landeras-Bueno, Chun-Teng Huang, Daniil M. Prigozhin, Joseph G. Gleeson, Alexey Terskikh, Pei-Yong Shi, Sujan Shresta
Summary: Zika virus and dengue virus co-circulate in many countries. This study found that Zika virus strains passaged in cultured mosquito cells exhibit increased pathogenesis in dengue virus-immune mice. A specific mutation was identified to enhance Zika virus replication.
Article
Allergy
Hussin A. Rothan, Siddappa N. Byrareddy
Summary: MIS-C, a condition in children during the COVID-19 pandemic, generates global concern, with main symptoms including fever, diarrhea, shock, and other manifestations; despite the presence of antibodies, severe complications can still occur.
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Aathe Cangaree Arumugam, Fatima Ezzahra Agharbaoui, Ahmad Suhail Khazali, Rohana Yusof, Noorsaadah Abd Rahman, Abdullah Al Hadi Ahmad Fuaad
Summary: Dengue virus infection is a major global public health concern, without any specific antiviral treatment. This study aims to develop small peptide inhibitors targeting the virus entry process to block infection. One of the designed peptides, AC 001, shows the ability to reduce 40% of DV plaque formation. Computational analysis reveals the key residues involved in the binding of these peptides to the virus protein pocket.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Hussin A. Rothan, Teow Chong Teoh
Summary: The emergence of SARS-CoV-2 has impacted global public health, prompting innovative strategies for antiviral drug development. The identification of variants has made antiviral drug screening more attractive. A successful cell-based assay protocol was designed and validated for screening antiviral drug inhibitors against SARS-CoV-2, leading to the discovery of a new class of viral protease inhibitors.
MOLECULAR BIOTECHNOLOGY
(2021)
Article
Virology
Pratima Kumari, Hussin A. Rothan, Janhavi P. Natekar, Shannon Stone, Heather Pathak, Philip G. Strate, Komal Arora, Margo A. Brinton, Mukesh Kumar
Summary: The study demonstrated that SARS-CoV-2 infection can lead to neuroinvasion and encephalitis in K18-hACE2 mice, resulting in mortality. While the highest virus titers were observed in the lungs, high levels of infectious virus were also found in the brains of the infected mice. The severity of the disease in infected mice correlated with peak viral levels in the brain.
Article
Biochemistry & Molecular Biology
Vertika Gautam, Piyarat Nimmanpipug, Sharifuddin Md Zain, Noorsaadah Abd Rahman, Vannajan Sanghiran Lee
Summary: ERK1/2 inhibitors play a crucial role in promoting cell survival and proliferation, but the reactivation of ERK1/2 signaling leads to drug resistance. These inhibitors have shown clinical efficacy as a therapeutic strategy for tumors with MAPK upstream target mutations, and may also be used to overcome acquired resistance to MAPK inhibitors.
Article
Biochemistry & Molecular Biology
Mohammad G. Al-Thiabat, Amirah Mohd Gazzali, Noratiqah Mohtar, Vikneswaran Murugaiyah, Ezatul Ezleen Kamarulzaman, Beow Keat Yap, Noorsaadah Abd Rahman, Rozana Othman, Habibah A. Wahab
Summary: Drug targeting research focusing on folate receptor alpha (FR alpha) as a biological marker in cancer drug delivery has shown that the conjugation of folic acid (FA) with beta-cyclodextrin (beta CD) improves stability and decreases mobility of residues in the system. This conjugation creates a more dynamically stable system with FR alpha, with favorable energy contributions from specific residues, ultimately increasing the overall stability of the system.
Article
Energy & Fuels
Suraya Zulkepli, Hwei Voon Lee, Noorsaadah Abd Rahman, Ling Tau Chuan, Pau Loke Show, Wei-Hsin Chen, Joon Ching Juan
Summary: The interest in sustainable hydrocarbon-like biofuel production is increasing, and Fe/HMS catalyst has shown potential in efficiently producing diesel-range biofuel. The catalyst's performance is attributed to well-dispersed Fe in the hematite phase, interaction between Si-OH and Fe-O bonds, acidity, surface area, and pore size enhancements. This result indicates Fe/HMS catalyst as a potential DO catalyst for renewable hydrocarbon-like biofuel production.
Article
Chemistry, Physical
Wei Lim Chong, Visit Vao-soongnern, Piyarat Nimmanpipug, Chatchai Tayapiwatana, Jung-Hsin Lin, Yi-Ling Lin, Hui Yee Chee, Sharifuddin Md Zain, Noorsaadah Abd Rahman, Vannajan Sanghiran Lee
Summary: In this study, designed ankyrin repeat proteins (DARPins) were explored for their potential in mimicking the interactions of antibodies to bind with domain III (DIII) E protein of dengue virus (DENV). Molecular docking, molecular dynamics simulations, and free energy calculations were performed to improve the binding affinity of DARPins for DIII DENV-2. The correlation between global mode shape and binding free energy was observed, providing valuable tools for understanding the structural dynamics and energy contribution in designing DARPins to bind with the E protein of DENV-2.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemistry & Molecular Biology
Fiona Seh-Lin Keng, Siew-Moi Phang, Noorsaadah Abd Rahman, Hui-Yin Yeong, Gill Malin, Emma Leedham Elvidge, William Sturges
Summary: The study investigated the effects of temperature on halocarbon emissions from four tropical seaweed species in Malaysia. The results demonstrated that the emission rates of halocarbons were influenced by temperature changes and exposure durations, with unique responses observed for each seaweed species.
Article
Virology
Shannon Stone, Hussin Alwan Rothan, Janhavi Prasad Natekar, Pratima Kumari, Shaligram Sharma, Heather Pathak, Komal Arora, Tabassum Tasnim Auroni, Mukesh Kumar
Summary: Emerging SARS-CoV-2 variants have a greater potential for infectivity and adaptation to new hosts. They are capable of high-concentration replication in the lungs, leading to upregulation of cytokines and chemokines, as well as histopathological changes in the lungs.
Article
Microbiology
Hussin A. Rothan, Pratima Kumari, Shannon Stone, Janhavi P. Natekar, Komal Arora, Tabassum T. Auroni, Mukesh Kumar
Summary: This study investigates the neuropathogenesis of SARS-CoV-2 infection in transgenic K18-hACE2 mice. The researchers found that neurons obtained from K18-hACE2 mice are susceptible to SARS-CoV-2 infection and support virus replication. Additionally, SARS-CoV-2 infection upregulates the expression of genes involved in innate immunity and inflammation in neurons and mouse brains. The study also reveals activation of the ZBP1/pMLKL-regulated necroptosis pathway in SARS-CoV-2-infected neurons and mouse brains.
Article
Virology
Janhavi Prasad Natekar, Heather Pathak, Shannon Stone, Pratima Kumari, Shaligram Sharma, Tabassum Tasnim Auroni, Komal Arora, Hussin Alwan Rothan, Mukesh Kumar
Summary: This study evaluated the pathogenesis of different variants of SARS-CoV-2 in mice expressing human ACE-2. The B.1.1.7, B.1.351, and B.1.617.2 variants were found to be more lethal and resulted in higher viral titers in the lungs and brain compared to the original B.1 strain. Interestingly, the B.1.1.529 variant showed less severe clinical signs and higher survival rates. Transcription levels of cytokines and chemokines were lower in mice infected with B.1 and B.1.1.529 compared to other variants.
Review
Pharmacology & Pharmacy
Yi Wen Lim, Wen Siang Tan, Kok Lian Ho, Abdul Razak Mariatulqabtiah, Noor Hayaty Abu Kasim, Noorsaadah Abd Rahman, Tin Wui Wong, Chin Fei Chee
Summary: This review discusses the challenges in developing PLGA-based long-acting injectable/implantable drug products, focusing on the issues related to drug encapsulation and release, and provides approaches to overcome these challenges and hurdles.
Article
Multidisciplinary Sciences
Mohd Hafiz Ahmad, Wageeh A. Yehye, Noorsaadah Abd Rahman, Lina A. Al-Ani, Mohd Rafie Johan, Jun Lu, Najihah M. Hashim
Summary: The functionalization of sulfur-containing butylated hydroxytoluene ligands (S-BHTLs) with gold nanoparticles has shown enhanced antioxidant and cytotoxic abilities, making them promising anticancer agents.
CHIANG MAI JOURNAL OF SCIENCE
(2021)
