Article
Biochemistry & Molecular Biology
Yifei Wu, Scott D. D. Pegan, David Crich, Lei Lou, Lauren Nicole Mullininx, Edward B. B. Starling, Carson Booth, Andrew Edward Chishom, Kuan Y. Y. Chang, Zhong-Ru Xie
Summary: Papain-like protease (PLpro) plays a critical role in COVID-19 infection and is an important target protein for drug development. Through virtual screening, we identified several drug candidates with convincing binding affinities to the PLpro of SARS-CoV-2. The docking results and analysis showed consistency between the computational approaches and biological experiments, suggesting the potential of these identified compounds for COVID-19 treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Elyasa Mustafa Elfaki, Hassan H. Alhassan, Mehnaz Kamal, Maher M. Al-Enazi, Malik Abdul Rub, Abdullah M. Asiri, Maroof Ali, Hadi M. Marwani, Salem Hussain Alharethi, Maha Moteb Alotaibi, Naved Azum
Summary: Tyrosine-protein kinase CSK, also known as C-terminal Src kinase (CSK), plays important roles in regulating diverse cellular processes and pathways, including cell growth, differentiation, migration, and immune responses. Aberrant expression of CSK has been associated with various diseases, such as cancer and autoimmune disorders. This study conducted a structure-based virtual screening of phytochemicals to identify potential CSK inhibitors. Two hits (Shinpterocarpin and Justicidin B) were selected based on their druglike properties and binding affinity towards CSK. Molecular dynamics simulations further confirmed their potential as selective CSK inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Yue Zhang, Jiankun Song, Yuanzhang Zhou, Huijun Jia, Tianyu Zhou, Yingbo Sun, Qiong Gao, Yue Zhao, Yujie Pan, Zhaolin Sun, Peng Chu
Summary: Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development and immune reprogramming, and has been proposed as a potential therapeutic target for cancer. Rottlerin and Morusin were discovered as selective and potent USP22 inhibitors, which can increase histone ubiquitination levels and reduce the expression of Sirt1 and PD-L1 proteins. These findings suggest that Rottlerin and Morusin may have potential as drugs for anticancer therapy.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Simon Leiris, David T. Davies, Nicolas Sprynski, Jerome Castandet, Lilha Beyria, Michael S. Bodnarchuk, Jonathan M. Sutton, Toby M. G. Mullins, Mark W. Jones, Andrew K. Forrest, T. David Pallin, Paduri Karunakar, Sathish Kumar Martha, Battu Parusharamulu, Ramesh Ramula, Venkatesh Kotha, Narender Pottabathini, Srinivasu Pothukanuri, Marc Lemonnier, Martin Everett
Summary: Novel therapies are needed to treat chronic bacterial infections in cystic fibrosis (CF) sufferers, with Pseudomonas aeruginosa being a common pathogen responsible for these infections. P. aeruginosa elastase, also known as LasB, is a key virulence determinant in CF patients and a potential target for adjuvant drug development. Through virtual screening and computer assisted drug design (CADD), a new series of LasB inhibitors have been discovered and optimized, with compounds 29 and 39 showing promising inhibitory activity.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
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, Multidisciplinary
Arjun Prasad Timilsina, Bimal Kumar Raut, Chen Huo, Karan Khadayat, Prakriti Budhathoki, Mandira Ghimire, Rabin Budhathoki, Niraj Aryal, Ki Hyun Kim, Niranjan Parajuli
Summary: Metabolomics and molecular networking approaches have been rapidly advancing in the field of biological sciences, allowing for the systematic identification and characterization of bioactive metabolites in natural products. This study focused on evaluating the potential of four medicinal plants in inhibiting enzymatic activity and annotating secondary metabolites.
Article
Engineering, Multidisciplinary
Walaa S. Sakr, Ragab A. EL-Sehiemy, Ahmed M. Azmy, Hossam A. Abd el-Ghany
Summary: This paper presents a novel methodology to identify the optimal border of a virtual power plant (VPP), the optimal number and location of distributed generations within the VPP, and the optimal value and location of dispatchable load. The proposed methodology considers uncertainties related to VPP components and has been validated through simulation results on real-world power systems. The results demonstrate the effectiveness and feasibility of the approach.
ALEXANDRIA ENGINEERING JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Madhulata Kumari, Mohd Waseem, Naidu Subbarao
Summary: In this study, a ligand-based scaffold model was generated to identify multi-targeting inhibitors as potential antitubercular agents. Through molecular docking and molecular dynamics simulations, compound HPT was identified as a potent anti-mycobacterial inhibitor with good binding affinity to multiple mur enzymes of Mtb. This computational study provides a lead scaffold based on 5'-O-(5-Amino-5-deoxy-beta-D-ribofuranosyl)uridine for the development of more effective pharmaceutical molecules targeting multiple mur enzymes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Immunology
Fan Zhou, Lena Hansen, Gabriel Pedersen, Gunnveig Grodeland, Rebecca Cox
Summary: Our study demonstrates that the Matrix M adjuvanted virosomal H5N1 vaccine can induce rapid and robust broadly cross-neutralizing antibody responses, providing comprehensive protection. The adjuvanted vaccines also induce multifaceted antibody responses, including hemagglutinin stalk domain specific, neuraminidase inhibiting, and antibody-dependent cellular cytotoxicity inducing antibodies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaoyu Ding, Zijie Zhao, Yue Wu, Hao Zhang, Kaixian Chen, Cheng Luo, Xiaomin Luo, Heng Xu
Summary: The study evaluated binding sites of Nur77 with small molecules and discovered compound 13e with the strongest binding affinity, predicting its binding mode. This compound showed significant anti-inflammatory activity in TNF-α-induced HepG2 cell model.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rania Hamdy, Bahgat Fayed, Ahmed Mostafa, Noura M. Abo Shama, Sara Hussein Mahmoud, Chetan Hasmukh Mehta, Yogendra Nayak, Sameh S. M. Soliman
Summary: Through virtual screening and biological evaluation, a novel compound named M3 with promising dual activity against SARS-CoV-2 was discovered, deserving further investigation for potential clinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Garland Kgosi More, Jacques Vervoort, Paul Anton Steenkamp, Gerhard Prinsloo
Summary: This study investigates twenty medicinal plants with previously established anti-viral activity against a wild-type RVFV using bio-chemometric and analytical techniques. The aim is to identify common compounds in the plants that contribute to the anti-viral effect. Proton nuclear magnetic resonance (H-1 NMR) spectroscopy and multivariate data analysis (MVDA) were used to characterize metabolite profiles. The study identifies potential metabolites, such as trigonelline and vanillic acid, as well as the presence of hydroxylated fatty acids, which have not been previously reported in all tested plants with high anti-RVFV activity. These findings provide insight into the metabolomic profile of anti-RVFV plant extracts and suggest potential targets for the development of antiviral therapeutic agents.
Article
Biology
Raj Kumar, Vikas Kumar, Keun Woo Lee
Summary: The study identified potential inhibitors against COVID-19 using a combination of virtual screening, molecular dynamics simulations, and binding free energy approaches. Ceftaroline fosamil and telaprevir were found to be effective inhibitors against M-pro. Further preclinical testing is suggested to validate their potential as treatments for COVID-19.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yang Gao, Ziying Zhou, Tingting Zhang, Situ Xue, Ke Li, Jiandong Jiang
Summary: The study identified a potential therapeutic compound for HCC, ZZY-19, which targets ULK1 and inhibits autophagy induction by reducing the expression of ULK1. ZZY-19 exhibited anti-proliferative, anti-invasive, and anti-migratory effects on HCC cells, and when combined with sorafenib, it synergistically suppressed HCC progression in vivo.
Article
Biochemistry & Molecular Biology
Shilpi Sarkar, Thirukumaran Kandasamy, Rajib Shome, Siddhartha Sankar Ghosh
Summary: This study highlights the involvement of epigenomic reprogramming and the role of p300 in breast cancer. By using virtual screening and molecular docking, two potential repurposed drugs, Netarsudil and Imatinib, were identified as inhibitors of p300 activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Citra Dewi, Adryan Fristiohady, Riezki Amalia, Edwin J. Bunggulawa, Muchtaridi Muchtaridi
Summary: This study investigates the molecular docking and dynamics simulations of alpha-mangostin on glycogen synthase kinase 3 beta (GSK3 beta). The results show that alpha-mangostin has a weaker binding affinity to GSK3 beta compared to the native ligand but shares similar docking sites. This suggests that alpha-mangostin may have potential as an anti-TNBC agent.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Wiwit Nurhidayah, Eva Maria Widyasari, Isti Daruwati, Isa Mahendra, Toto Subroto, Nur Kusaira Khairul Ikram, Muchtaridi Muchtaridi
Summary: The high incidence and mortality rate of breast cancer highlight the urgent need to develop new diagnostic and therapeutic agents. Alpha mangostin (AM), a natural compound, has shown potential in inhibiting breast cancer. This study aims to prepare [I-131]I-AM and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Muchtaridi Muchtaridi, Dian Triwahyuningtyas, Taufik Muhammad Fakih, Sandra Megantara, Sy Bing Choi
Summary: In this study, in silico techniques including molecular docking and molecular dynamics simulation were used to explore the molecular mechanism and stability of the encapsulation of alpha-mangostin using cyclodextrins. The results showed that the encapsulation of alpha-mangostin with 2-hydroxypropyl-beta-cyclodextrin can increase its solubility and provide good stability.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Mohammad Adam Mustapa, Ikhsan Guswenrivo, Ade Zurohtun, Nur Kusaira Khairul Ikram, Muchtaridi Muchtaridi
Summary: This research study focused on developing essential oil-based repellent activity tests against Aedes aegypti mosquitoes. The steam distillation method was used to isolate essential oils, and 10% essential oil repellents were tested on volunteers' arms using virus-free Aedes aegypti mosquitoes. The analysis of essential oil activities and aroma components was conducted using headspace repellent and GC-MS methods. The results showed that patchouli and cinnamon had the highest average repellent power, and the chemical compounds in these oils have the potential to be environmentally friendly mosquito repellents.
Review
Pharmacology & Pharmacy
Yedi Herdiana, Nasrul Wathoni, Dolih Gozali, Shaharum Shamsuddin, Muchtaridi Muchtaridi
Summary: Despite recent advances, cancer remains the leading cause of death globally. Research has been conducted to find new and effective anticancer medications, with a focus on the complexity of breast cancer. Chitosan nanoparticles (CSNPs) have emerged as a promising drug delivery system, enhancing drug activity and minimizing harm to normal cells. The use of smart drug delivery systems (SDDs) to improve the bioactivity of CSNPs and understand breast cancer intricacies has gained significant interest. This review explores the potential of CSNPs as SDDs for targeted cancer therapy and stimulus response medication delivery.
Review
Multidisciplinary Sciences
Luthfi Utami Setyawati, Wiwit Nurhidayah, Nur Kusaira Khairul Ikram, Wan Ezumi Mohd Fuad, Muchtaridi Muchtaridi
Summary: A systematic review was conducted to summarize the research on the safety profile of mangosteen pericarp (GM) containing alpha mangostin (AM). The LD50 and NOAEL values of AM were determined through general toxicity tests. The results provide valuable information for the development of GM-or-AM-based products.
Article
Biochemistry & Molecular Biology
Ida Musfiroh, Mus Ifaya, I. Sahidin, Dewi M. D. Herawati, Ami Tjitraresmi, Syawal Abdurrahman, Muchtaridi Muchtaridi, Nur Kusaira Khairul Ikram
Summary: This study found that the phenolic compound luteolin isolated from henna leaves has the potential as an anti-diabetic agent, demonstrated by its ability to suppress the digestion of the alpha-amylase enzyme. Molecular docking experiments showed strong binding energy between the compound and both alpha-amylase and alpha-glucosidase enzymes, indicating its efficacy. Additionally, molecular dynamics simulations and ADME-Tox modeling supported its characteristics and potential as a treatment option for diabetes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Physical
Erich Hellemann, Jacob D. Durrant
Summary: Structure-based virtual screening is effective for identifying potential small-molecule ligands. However, traditional approaches struggle to find ligands that bind to alternate conformations. Ensemble docking addresses this issue but requires methods to thoroughly explore pocket flexibility. We introduce Sub-Pocket EXplorer (SubPEx), which uses weighted ensemble path sampling to accelerate binding-pocket sampling.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Polymer Science
Arif Budiman, Neng Vera Nurani, Eli Laelasari, Muchtaridi Muchtaridi, Sriwidodo Sriwidodo, Diah Lia Aulifa
Summary: This study aimed to characterize the interaction between a drug and polymer in amorphous solid dispersions (ASDs) and evaluate the impact on the physical stability and dissolution of alpha-mangostin (AM). The presence of polymers significantly improved the solubility and dissolution rate of AM, but the extent of this improvement varied depending on the polymer and storage conditions.
Review
Food Science & Technology
Cokorda Istri Sri Arisanti, I. Made Agus Gelgel Wirasuta, Ida Musfiroh, Emmy Hainida Khairul Ikram, Muchtaridi Muchtaridi
Summary: This study provides an overview of the compounds in sweet potato that contribute to its anti-diabetic activity and the mechanisms by which they act. A comprehensive literature search retrieved 269 articles, and after applying inclusion and exclusion criteria, 28 articles were selected for further review. The findings identified four varieties of sweet potato with potential anti-diabetic properties, and phenolic acids, flavonols, flavanones, and anthocyanidins were determined to be responsible for the anti-diabetic activity.
Article
Biology
Nur Kusaira Khairul Ikram, Ali Muhammad Zakariya, Mohd Zuwairi Saiman, Arman Beyraghdar Kashkooli, Henrik Toft Simonsen
Summary: Artemisinin is a commercially important natural medicinal compound known for its antimalarial activity. Its low accumulation in the native plant and difficult chemical synthesis have hindered its production and commercialization. To overcome this, a technique involving the direct in vivo assembly of DNA fragments in the moss, P. patens, was successfully established for the heterologous production of artemisinin. This bioengineering approach provides a more sustainable, cost-effective, and scalable platform not only for artemisinin production but also for other high-value specialized metabolites in the future.
Article
Pharmacology & Pharmacy
Isti Daruwati, Abednego Gwiharto, Hendris Wongso, Tri Achmad, Mukh Syaifudin, Muchtaridi Muchtaridi
Summary: The synthesis of \[I-131\]beta-estradiol was successfully carried out, and its radiochemical purity and presence of chemical impurities were measured using HPLC.
JOURNAL OF ADVANCED PHARMACEUTICAL TECHNOLOGY & RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yedi Herdiana, Nasrul Wathoni, Shaharum Shamsuddin, Muchtaridi Muchtaridi
Summary: In this study, folate-conjugated chitosan nanoparticles (F-CS-NPs) were developed as a delivery system for alpha-mangostin (AM) to enhance its cytotoxicity to cancer cells. The use of F-CS-NPs significantly improved the cytotoxicity of AM against MCF-7 breast cancer cells.