Article
Biochemistry & Molecular Biology
Alejandro Llanes, Hector Cruz, Viet D. Nguyen, Oleg V. Larionov, Patricia L. Fernandez
Summary: In the study, two molecular docking simulation approaches were used to explore the interaction of four libraries of semisynthetic nitrogenous heterocyclic compounds with the SARS-CoV-2 causative agent M-pro. The flexible docking approach seemed to provide a more realistic representation of interactions within the active site. Selected compounds with favorable energy estimates could potentially serve as antiviral agents against SARS-CoV-2.
Article
Biochemistry & Molecular Biology
Laurent Soulere, Thibaut Barbier, Yves Queneau
Summary: Comparative analysis of amino acid sequences and 3D structural alignment revealed significant structural homologies between the main proteases of SARS-CoV-2 and IBV. In silico screening using a PubChem BioAssay database identified four covalent inhibitors and five non-covalent inhibitors for SARS-CoV-2 protease. Molecular dynamics simulations further investigated the binding of these inhibitors, and predictive ADMET calculations suggested promising pharmacokinetic properties for the nine compounds.
Article
Chemistry, Medicinal
Mohsen Sisakht, Amir Mahmoodzadeh, Maryam Darabian
Summary: A dataset of plant-based natural compounds was screened for antiviral activity against SARS-CoV-2 main protease, with several phytochemicals identified as potential inhibitors that could be used in the fight against COVID-19.
PHYTOTHERAPY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Raju Das, Sarmin Ummey Habiba, Raju Dash, Yohan Seo, Joohan Woo
Summary: In this study, potential shikonin derivatives targeting the M-pro of COVID-19 were identified using molecular docking and molecular dynamics simulations. Several derivatives showed higher binding affinity than shikonin. Molecular dynamics simulation studies revealed that these derivatives interacted with conserved residues in the catalytic sites of the M-pro, suggesting their potential role in inhibiting SARS-CoV-2 progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Suwicha Patnin, Arthit Makarasen, Pongsit Vijitphan, Apisara Baicharoen, Apinya Chaivisuthangkura, Mayuso Kuno, Supanna Techasakul
Summary: In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and SARS-CoV-2 main protease (M-pro) were investigated, and two compounds were found to have low binding energy values and appropriate molecular properties for binding to M-pro via hydrogen bonding and Pi-Pi stacking interactions.
Article
Biochemistry & Molecular Biology
Fangya Li, Tingting Fang, Feng Guo, Zipeng Zhao, Jianyu Zhang
Summary: In this study, we investigated the kinetic behaviors of M-pro from SARS-CoV-2 and SARS-CoV using FRET-based cleavage assay and LC-MS method. Our findings suggest that the FRET-based cleavage assay can be used for preliminary screening of M-pro inhibitors, while the LC-MS method is more reliable for selecting effective inhibitors. Additionally, we constructed active site mutants (H41A and C145A) and measured the kinetic parameters to understand the enzyme efficiency reduction at the atomic level. Overall, our study provides valuable insights for inhibitor screening and design by comprehensively understanding M-pro's kinetic behaviors.
Article
Biochemical Research Methods
Nicia Rosario-Ferreira, Salete J. Baptista, Carlos A. Barreto, Filipe E. P. Rodrigues, Tomas F. D. Silva, Sara G. F. Ferreira, Joao N. M. Vitorino, Rita Melo, Bruno L. Victor, Miguel Machuqueiro, Irina S. Moreira
Summary: This study introduced computational protocols for targeting the SARS-CoV-2 main protease, including uploading, visualizing, and managing three-dimensional structures, homology modeling, protein-ligand docking, virtual screening, and molecular dynamics simulations. These protocols offer important insights into addressing one of the biggest biological problems currently facing the world.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daoqun Li, Junwen Luan, Leiliang Zhang
Summary: The study identified potential inhibitors of the SARS-CoV-2 papain-like protease using an in silico molecular docking approach, with Neobavaisoflavone showing the highest binding energy. These compounds may be promising candidates for therapeutic intervention against COVID-19 by targeting crucial catalytic residues of the protease.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Xinbo Yang, Xianrong Xing, Yirui Liu, Yuanjie Zheng
Summary: This study proposes a virtual drug screening method based on the M-pro structure to identify potential therapeutic drugs for COVID-19. Five compounds were found to have potential inhibitory effects on the SARS-CoV-2 M-pro, and further experimental verification was carried out.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wei Wei, Ni Kong, Meng-Zhen Liu, Ting Han, Jun-Feng Xu, Chong Liu
Summary: This study found that anisodamine suppressed SARS-CoV-2 infection in Vero E6 cells and reduced SARS-CoV-2 pseudovirus entry in HEK293/hACE2 cells. Molecular docking studies suggested that anisodamine may target SARS-CoV-2 main protease (Mpro) with a docking score of -6.63 kcal/mol and form three hydrogen bonds at the predicted active site of Mpro.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Davide Bassani, Matteo Pavan, Giovanni Bolcato, Mattia Sturlese, Stefano Moro
Summary: This study investigates the performance variation of three docking algorithms, GOLD, Glide, and PLANTS, in replicating the coordinates of crystallographic ligands of SARS-CoV-2 main protease. The importance of solvent exposure in docking performance is highlighted through the comparison of docking data and values derived from solvent exposure calculations. Molecular dynamics simulations further confirm that protein-ligand complexes with higher solvent exposure tend to be less stable.
Article
Biology
Amir Hossein Arshia, Shayan Shadravan, Aida Solhjoo, Amirhossein Sakhteman, Ashkan Sami
Summary: The study focused on identifying potential inhibitors against the main protease of SARS-CoV-2 using computational approaches, such as molecular docking and molecular dynamics simulations. The selected candidates showed strong interaction with key residues, validated through extensive computational and statistical analyses. Further in vitro, in vivo, and clinical trials are needed to confirm their efficacy.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
M. Elizabeth Sobhia, Ketan Ghosh, Srikanth Sivangula, Siva Kumar, Harmanpreet Singh
Summary: This study utilized computer simulation methods to identify molecules that have the potential to inhibit the SARS-CoV-2 main protease. The selected molecules showed stability in complex and intermolecular hydrogen bond analysis confirmed their thermodynamic stability. This study also has the potential to guide the determination of other ligand-main protease complex structures using X-ray diffraction methods.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Shaban Ahmad, Mussuvir K. M. Pasha, Khalid Raza, Misbahuddin M. Rafeeq, Alaa Hamed Habib, Murugesh Eswaran, Manoj Kumar Yadav
Summary: This study identifies dianicilib and theodrenaline as potential drugs against multiple drug targets of SARS-CoV-2 through molecular docking and simulation studies. These drugs show reliable binding to multiple targets and have the potential to disrupt the activity of the virus in different variants.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Hai Ping Shao, Tian Hua Wang, Hong Lin Zhai, Ke Xin Bi, Bing Qiang Zhao
Summary: In this study, the interaction mechanisms of two representative peptide inhibitors (11a and PF-07321332) with SARS-CoV-2 main protease (Mpro) were investigated for the first time using molecular dynamics simulation. Fragment-based drug design method was then employed to select fragments from existing SARS-CoV and SARS-CoV-2 inhibitors to replace the original P2 and P3 fragments, resulting in new molecules. Molecular docking, molecular dynamics simulation, and ADMET properties prediction confirmed the excellent activity and physicochemical properties of two molecules (O-74 and N-98), suggesting their potential as new inhibitors for SARS-CoV-2 main protease.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Applied
Omnia Hesham Abdelhafez, John Refaat Fahim, Muhamad Mustafa, Asmaa M. AboulMagd, Samar Yehia Desoukey, Alaa M. Hayallah, Mohamed Salah Kamel, Usama Ramadan Abdelmohsen
Summary: The study identified 14 structurally diverse minor constituents from the Red Sea soft coral Nephthea sp. as potential sources of anti-COVID-19 agents, with compound (1) showing the highest binding capacity and acceptable drug-likeness properties.
NATURAL PRODUCT RESEARCH
(2022)
Article
Plant Sciences
Eman Zekry Attia, Basma Ali Khalifa, Gehan M. Shaban, Wedad M. Abdelraheem, Muhamad Mustafa, Usama Ramadan Abdelmohsen, Mo'men H. El-Katatny
Summary: Continuous resistance of Pseudomonas aeruginosa to traditional antibacterial drugs due to biofilm formation has resulted in a growing need for effective antibiofilm formation treatments. This study identified potential antibiofilm agents from the endophytic Penicillium chrysoginum AJEF2 and found that a modified culture medium exhibited significant antibacterial potential against various human pathogenic microorganisms and inhibited biofilm formation by Pseudomonas aeruginosa clinical isolates. Molecular docking simulation identified specific metabolites that showed potential for inhibiting biofilm formation. These findings highlight the potential of endophytic Penicillium chrysoginum AJEF2 as a source for antibiofilm compounds.
SOUTH AFRICAN JOURNAL OF BOTANY
(2022)
Article
Chemistry, Medicinal
Soad A. Mohamed, Mohamed A. Abdelgawad, Rania Alaaeldin, Zeinab Fathalla, Hossam Moharram, Raafat M. A. Abdallah, Islam M. Abdel-Rahman, Mohamed Abdel-Aziz, Gamal El-Din A. Abuo-Rahma, Mohammed M. Ghoneim, Alaa M. Hayallah, Mahmoud Elrehany, Hamdy Abdelkader
Summary: This study successfully developed newly synthesized ciprofloxacin derivative (2b) niosomes and Solulan C24-modified niosomes for treating keratitis. Results showed that both 2b niosomes and discomes were superior to conventional eye drops and could be effectively formulated at physiological pH for treating keratitis.
Article
Microbiology
Iart Luca Shytaj, Mohamed Fares, Lara Gallucci, Bojana Lucic, Mahmoud M. Tolba, Liv Zimmermann, Julia M. Adler, Na Xing, Judith Bushe, Achim D. Gruber, Ina Ambiel, Ahmed Taha Ayoub, Mirko Cortese, Christopher J. Neufeldt, Bettina Stolp, Mohamed Hossam Sobhy, Moustafa Fathy, Min Zhao, Vibor Laketa, Ricardo Sobhie Diaz, Richard E. Sutton, Petr Chlanda, Steeve Boulant, Ralf Bartenschlager, Megan L. Stanifer, Oliver T. Fackler, Jakob Trimpert, Andrea Savarino, Marina Lusic
Summary: The lack of effective antiviral treatments against SARS-CoV-2 is a significant limitation in the fight against the COVID-19 pandemic. This study highlights cobicistat as a potential therapeutic candidate for treating SARS-CoV-2 infection and as a building block for combination therapies for COVID-19. Cobicistat inhibits SARS-CoV-2 replication through the inhibition of spike protein-mediated membrane fusion and enhances the antiviral effect of remdesivir.
Review
Nutrition & Dietetics
Moustafa Fathy, Sahar M. Saad Eldin, Muhammad Naseem, Thomas Dandekar, Eman M. Othman
Summary: Nature provides a rich source of biologically active compounds, including the plant hormone cytokinins which play a crucial role in cell division and development. Recent studies have shown that cytokinins also have effects on mammalian cells, leading to research on their potential therapeutic applications in various human diseases and pathophysiological conditions.
Article
Critical Care Medicine
Kenichi Arai, Motonori Okabe, Daisuke Kobashi, Kenji Ichimura, Moustafa Fathy, Jiro Oba, Etsuko Furuichi, Satoshi Yoshida, Toshiko Yoshida
Summary: This study identified the stable housekeeping gene (TATA-binding protein) for studying gene expression in a third-degree burn injury model. The treatment with human amnion-derived mesenchymal cells promoted the formation of granulation tissue, differentiation of fibroblasts to myofibroblasts, and functional vascular structure in the wound healing process. The expression of angiogenic, pro-inflammatory and anti-inflammatory related mRNA was also influenced by the treatment, promoting the infiltration of endothelial cells and differentiation of M1 and M2 macrophages.
JOURNAL OF BURN CARE & RESEARCH
(2023)
Article
Medicine, Research & Experimental
Michael A. Fawzy, Gehad Nasr, Fares E. M. Ali, Moustafa Fathy
Summary: This study aimed to investigate the regulatory effects of quercetin (QU) on selected phosphodiesterase inhibitors against alpha-naphthyl isothiocyanate (ANIT)-induced acute intrahepatic cholestasis. The combination treatment of QU with sildenafil (Sild) or pentoxifylline (PTX) showed promising hepatoprotective effects and anti-cholestatic properties in improving ANIT-induced liver injury.
Article
Biochemistry & Molecular Biology
Rania Alaaeldin, Islam M. Abdel-Rahman, Fares E. M. Ali, Amany Abdlrehim Bekhit, Eyad Y. Elhamadany, Qing-Li Zhao, Zheng-Guo Cui, Moustafa Fathy
Summary: This study synthesized a novel ciprofloxacin derivative that exhibited dual inhibition of topo I and topo II enzymes, leading to the suppression of cancer cell proliferation, migration, and colony formation. It also induced apoptotic and necro-apoptotic pathways, activating the cleaved caspase 3, RIPK1, RIPK3, and MLKL proteins.
Article
Cell Biology
Rania Alaaeldin, Sally M. Bakkar, Reham H. Mohyeldin, Fares E. M. Ali, Nehad M. Reda Abdel-Maqsoud, Moustafa Fathy
Summary: The study aimed to investigate the nephroprotective activity of azilsartan on renal ischemia/reperfusion injury in rats. The results showed that azilsartan exhibited nephroprotective effects by exerting antioxidant, anti-inflammatory, anti-apoptotic activities, and inhibiting the HMGB1/NF-kappa B/p38/ERK1/2/JNK signaling pathway in rats with renal IR injury.
Article
Medicine, Research & Experimental
Mahmoud Abdelnaser, Rania Alaaeldin, Mina Ezzat Attya, Moustafa Fathy
Summary: This study examined the potential hepatoprotective activity of gabapentin on cecal ligation and puncture-induced sepsis in rats. The results showed that gabapentin could alleviate liver damage, reduce inflammation, inhibit apoptosis, and regulate intracellular signaling pathways and gene expression.
Article
Biochemistry & Molecular Biology
Maiiada H. Nazmy, Dalia H. Abu-baih, Mahmoud A. Elrehany, Muhamad Mustafa, Omar M. Aly, Azza A. K. El-Sheikh, Moustafa Fathy
Summary: The CA-4 analogue can attenuate human breast cancer cell proliferation by inducing apoptosis and simultaneously suppressing the MAPK/ERK and PI3K/AKT pathways.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Article
Pharmacology & Pharmacy
Mahmoud Abdelnaser, Rania Alaaeldin, Mina Ezzat Attya, Moustafa Fathy
Summary: This study aimed to evaluate the molecular effects of gabapentin on septic rats and found that gabapentin mitigated sepsis-related acute kidney injury through up-regulating the Nrf-2/HO-1 pathway, repressing apoptosis, and attenuating the oxidative stress status. It reduced levels of proinflammatory mediators and improved antioxidant status.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Cell & Tissue Engineering
Amany Abdlrehim Bekhit, Olivia N. Beshay, Michael A. Fawzy, Sara Mohamed Naguib Abdel-Hafez, Gaber El-Saber Batiha, Farid S. Ataya, Moustafa Fathy
Summary: This study aimed to explore the protective impact of azilsartan (AZIL), an antihypertensive drug, in addition to adipose tissue-derived mesenchymal stem cells (AD-MSCs) on cisplatin (CISP)-induced hepatotoxicity. The results showed that treatment with AZIL and AD-MSCs significantly alleviated CISP-induced liver damage and protected against oxidative stress, mitogen-activated protein kinase, and apoptotic pathways.
STEM CELLS INTERNATIONAL
(2023)
Article
Medicine, Research & Experimental
Reham H. Mohyeldin, Rania Alaaeldin, Ehab E. Sharata, Mina Ezzat Attya, Eyad Y. Elhamadany, Moustafa Fathy
Summary: Sepsis is a serious inflammatory response to infection with a high mortality rate worldwide. The combination of an angiotensin receptor blocker (valsartan) and a neprilysin inhibitor prodrug (sacubitril) showed significant hepatoprotective benefits in rats with CLP-induced sepsis, outperforming valsartan alone.
