Article
Multidisciplinary Sciences
Lin Lin, Da-Yuan Chen, Christina Scartelli, Huanzhang Xie, Glenn Merrill-Skoloff, Moua Yang, Lijun Sun, Mohsan Saeed, Robert Flaumenhaft
Summary: This study screened 1,019 plant-based flavonoids and identified compounds that can inhibit the SARS-CoV-2 main protease. The most potent inhibitors were apigenin and a galloylated pinocembrin analog called PGHG.
Article
Chemistry, Medicinal
Bin Tan, Michael Sacco, Haozhou Tan, Kan Li, Ryan Joyce, Xiujun Zhang, Yu Chen, Jun Wang
Summary: In the study, reactive warheads, including Jun11119R (vinyl sulfonamide warhead), Jun10221R (propiolamide warhead), Jun1112R (4-chlorobut-2-ynamide warhead), Jun10541R (nitrile warhead), and Jun10963R (dually activated nitrile warhead), were identified as potent Mpro inhibitors. Jun10541R and Jun10963R also showed strong antiviral activity against SARS-CoV-2 in Calu-3 cells, with EC50 values of 2.92 and 6.47 μM, respectively. X-ray crystal structures of Mpro with Jun10541R and Jun10221 demonstrated covalent modification of Cys145. These Mpro inhibitors with diverse reactive warheads hold promise for further development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Spectroscopy
Jinwen Li, Yantao Zhang, Huimin Pang, Shu Jie Li
Summary: Heparin interacts with SARS-CoV-2's M-pro and inhibits its activity, potentially playing a role in inhibiting the viral infection.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Biochemistry & Molecular Biology
Sin-Yee Fung, Kam-Leung Siu, Huayue Lin, Man Lung Yeung, Dong-Yan Jin
Summary: Both SARS-CoV and SARS-CoV-2 use NSPS proteins to antagonize IFN production, with variants like G15S and K90R retaining this antagonistic property.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Virology
Lukas van de Sand, Maren Bormann, Mira Alt, Leonie Schipper, Christiane Silke Heilingloh, Eike Steinmann, Daniel Todt, Ulf Dittmer, Carina Elsner, Oliver Witzke, Adalbert Krawczyk
Summary: The global pandemic of SARS-CoV-2 has had a significant impact on millions of people worldwide, highlighting the urgent need for novel antiviral compounds. The study demonstrated the antiviral activity of glycyrrhizin against SARS-CoV-2 and uncovered its mechanism of action by inhibiting the viral main protease. This suggests that glycyrrhizin-containing products, like licorice root tea, could benefit those infected with SARS-CoV-2 and warrants further investigation for clinical use in treating COVID-19 patients.
Article
Pharmacology & Pharmacy
Subodh Kumar Samrat, Jimin Xu, Xuping Xie, Eleonora Gianti, Haiying Chen, Jing Zou, Jason G. Pattis, Khaled Elokely, Hyun Lee, Zhong Li, Michael L. Klein, Pei-Yong Shi, Jia Zhou, Hongmin Li
Summary: In this study, researchers screened a drug library and identified JMX0286, JMX0301, and JMX0941 as potent allosteric inhibitors against SARS-CoV-2 3CLpro. They demonstrated the antiviral activity of these compounds through cell-based assays and characterized their mechanisms of action and binding sites.
ANTIVIRAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Weijuan Shang, Wenhao Dai, Cheng Yao, Ling Xu, Xiangming Tao, Haixia Su, Jian Li, Xiong Xie, Yechun Xu, Min Hu, Dong Xie, Hualiang Jiang, Leike Zhang, Hong Liu
Summary: FB2001 is a promising therapeutic agent in COVID-19 treatment that exhibits potent antiviral activity against various SARS-CoV-2 variants and shows improvement in pathological symptoms in the lungs and brains. It can be combined with remdesivir for better clinical outcomes. This drug candidate has been approved for Phase II/III clinical trial due to its good safety and tolerability.
ANTIVIRAL RESEARCH
(2022)
Article
Biology
Manish Manish, Smriti Mishra, Ayush Anand, Naidu Subbarao
Summary: This study utilized various computational methods and found that theaflavin digallate can strongly interact with the main protease of SARS-CoV-2, suggesting its potential as a drug candidate for inhibiting the virus.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Svetlana V. Belenkaya, Iuliia A. Merkuleva, Olga I. Yarovaya, Varvara Yu. Chirkova, Elena A. Sharlaeva, Daniil V. Shanshin, Ekaterina A. Volosnikova, Sergey Z. Vatsadze, Mikhail V. Khvostov, Nariman F. Salakhutdinov, Dmitriy N. Shcherbakov
Summary: Despite the long history and knowledge of E. coli, obtaining soluble recombinant proteins in this system can still be problematic. However, we have successfully used the 3CL protease from SARS-CoV-2 virus to transfer the target protein into the periplasmic space of E. coli. This protease showed higher catalytic efficiency compared to other commonly used proteases and can effectively work in E. coli cells.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yao Zhao, Yan Zhu, Xiang Liu, Zhenming Jin, Yinkai Duan, Qi Zhang, Chengyao Wu, Lu Feng, Xiaoyu Du, Jinyi Zhao, Maolin Shao, Bing Zhang, Xiuna Yang, Lijie Wu, Xiaoyun Ji, Luke W. Guddat, Kailin Yang, Zihe Rao, Haitao Yang
Summary: This study determines the high-resolution structures of SARS-CoV-2 M-Pro in different states, revealing the conformational changes that occur during substrate processing. The study also demonstrates the enzyme's specificity for certain sequences and provides a foundation for the development of new anti-SARS-CoV-2 drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Alexander M. Andrianov, Yuri V. Kornoushenko, Anna D. Karpenko, Ivan P. Bosko, Alexander V. Tuzikov
Summary: A computational approach was used to identify small drug-like compounds mimicking X77 for SARS-CoV-2 M-Pro inhibition. Five top-ranking compounds with high binding affinity to M-Pro were predicted, showing potential as scaffolds for novel antiviral agents targeting the active site of SARS-CoV-2 M-Pro.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Wenyue Cao, Chia-Chuan Dean Cho, Zhi Zachary Geng, Namir Shaabani, Xinyu R. Ma, Erol C. Vatansever, Yugendar R. Alugubelli, Yuying Ma, Sankar P. Chaki, William H. Ellenburg, Kai S. Yang, Yuchen Qiao, Robert Allen, Benjamin W. Neuman, Henry Ji, Shiqing Xu, Wenshe Ray Liu
Summary: The researchers developed an effective method to analyze the cellular potency of main protease (MPro) inhibitors for their toxicity and antiviral effect against SARS-CoV-2. Some antiviral agents showed weak cellular MPro inhibition potency, suggesting their involvement in interfering with other key steps in the virus life cycle. One of the inhibitors, MPI8, exhibited the highest cellular and antiviral potency, indicating the need for further research.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Elizabeth A. MacDonald, Gary Frey, Mark N. Namchuk, Stephen C. Harrison, Stephen M. Hinshaw, Ian W. Windsor
Summary: The main protease (Mpro) of SARS-CoV-2 plays a key role in viral replication by cleaving viral polyproteins at specific sites, and its interactions with substrates can have significant effects on catalytic efficiency. The study provides insights into potential targets for antiviral drug design and highlights the importance of finely tuned substrate-dependent catalytic parameters in the coronavirus lifecycle.
ACS INFECTIOUS DISEASES
(2021)
Review
Pharmacology & Pharmacy
Thales Kronenberger, Stefan A. Laufer, Thanigaimalai Pillaiyar
Summary: This article discusses the rationale for inhibitors targeting SARS-CoV-2 Mpro. Small molecules and peptidomimetic inhibitors are two types of inhibitors with different modes of action. Novel inhibitors discovered during the COVID-19 pandemic are highlighted, focusing on their binding modes and structures.
DRUG DISCOVERY TODAY
(2023)
Article
Pharmacology & Pharmacy
Montserrat Fabrega-Ferrer, Alejandra Herrera-Morande, Sara Muriel-Goni, Julia Perez-Saavedra, Paula Bueno, Victoria Castro, Urtzi Garaigorta, Pablo Gastaminza, Miquel Coll
Summary: Severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) are global public health threats. The study investigates the antiviral activity of the orally bioavailable enterovirus protease inhibitor AG7404 against SARS-CoV-1 and SARS-CoV-2, comparing it with rupintrivir. The results suggest that AG7404 has better fit to the active site of the target protease and exhibits greater inhibitory capacity than rupintrivir against both SARS-CoV-1 and SARS-CoV-2.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemical Research Methods
Marina Macchiagodena, Marco Pagliai, Piero Procacci
Summary: The study examined the non-covalent interaction between PF-07321332 and the SARS-CoV-2 main protease using computational methods. It found that the binding is likely to be stronger when the catalytic dyad is in a neutral state.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Chemistry, Physical
Gianluca Del Frate, Marina Macchiagodena, Muhammad Jan Akhunzada, Francesca D'Autilia, Andrea Catte, Nicholus Bhattacharjee, Vincenzo Barone, Francesco Cardarelli, Giuseppe Brancato
Summary: An integrated theoretical and experimental strategy was used to investigate the effect of environmental factors on the spectroscopic parameters of DPAP. The results showed that DPAP is sensitive to different environments, confirming its applicability as a probe for detecting different structures and levels of plasma membrane organization.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Physical
Piero Procacci, Guido Guarnieri
Summary: In this paper, blind predictions for the binding of WP6 with ammonium/diammonium cationic guests in the ninth challenge of SAMPL are presented. The binding free energies were calculated using a virtual double system single box approach and compared with previous submissions. The results show acceptable performance with higher accuracy than previous challenges, indicating the reliability of nonequilibrium approaches for binding free energy calculations.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Irene Vettori, Marina Macchiagodena, Marco Pagliai, Gavino Bassu, Emiliano Fratini, Piero Baglioni
Summary: This study investigates the structural and spectroscopic properties of HEMA and AA using computational and simulation methods. Two stable HEMA conformers are found to coexist, and their interactions with water are mainly through hydrogen bonding. IR spectra are used to differentiate the presence of conformers and obtain information on their ratio in the solution.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Chemistry, Multidisciplinary
Marina Macchiagodena, Marco Pagliai, Piero Procacci
Summary: We present a step-by-step protocol and toolkit for calculating the relative dissociation free energy (RDFE) using the GROMACS molecular dynamics package. This approach, based on a novel bidirectional nonequilibrium alchemical method, accurately computes RDFE between small molecules with different volume, charge, and chemical topology. The methodology is demonstrated using the challenging SAMPL9 batch of host-guest pairs. The article is supported by an online tutorial and a public Zenodo repository.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Margherita Verrucchi, Gina Elena Giacomazzo, Patrick Severin Sfragano, Serena Laschi, Luca Conti, Marco Pagliai, Cristina Gellini, Marilena Ricci, Enrico Ravera, Barbara Valtancoli, Claudia Giorgi, Ilaria Palchetti
Summary: A water-soluble ruthenium(II) complex (L) was used to modify the surface of an indium-tin oxide (ITO) electrode decorated with a nanostructured layer of TiO2 (TiO2/ITO). Singlet oxygen (O-1(2)) produced by the complex under visible light irradiation triggers a cathodic photocurrent when the electrode is illuminated and biased at a proper reduction potential. The L/TiO2/ITO electrode was characterized and demonstrated efficient oxidation of phenolic compounds, with a limit of detection (LOD) of 0.3 mu mol dm(-3).
Article
Biochemistry & Molecular Biology
Milana Bazayeva, Andrea Giachetti, Marco Pagliai, Antonio Rosato
Summary: Classical molecular dynamics (MD) simulations are commonly used to study the behavior of zinc(II)-proteins at the atomic level. In this study, the accuracy of two force fields (ZAFF and NBFF) in reproducing the dynamic behavior of zinc(II)-proteins was assessed using six zinc-fingers as benchmark. The results indicated that both force fields can accurately reproduce protein dynamics with comparable accuracy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Piero Procacci, Guido Guarnieri
Summary: We describe our blind prediction of the toluene-water partition coefficients in the SAMPL9 challenge. We used an efficient MD-based nonequilibrium alchemical technique relying on the GAFF2 non-polarizable force field. The prediction was optimized based on a pre-assessment comparing with known experimental data and provides valuable insights for improving the performance of the force field in drug-receptor system calculations.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Michele Casoria, Marina Macchiagodena, Paolo Rovero, Claudia Andreini, Anna Maria Papini, Gianni Cardini, Marco Pagliai
Summary: The standard GAFF2 force field parameterization has been refined for three fluorinated alcohols commonly used to study proteins and peptides in biomimetic media. The newly proposed models are validated through experimental findings, supporting their accuracy and effectiveness.
JOURNAL OF PEPTIDE SCIENCE
(2023)
Article
Chemistry, Physical
Piero Procacci
Summary: This study tested the performance of standard molecular dynamics (MD) simulations, replicates of shorter MD simulations, and Hamiltonian Replica Exchange (HREM) simulations for sampling in two macrocyclic hosts and a drug-receptor system. The results showed that enhanced sampling techniques were necessary for reliable sampling in the macrocycle with long-lived metastable states.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Angelo Mariano, Giulio D'Amato, Giovanni Formisano, Guido Guarnieri, Giuseppe Santomauro, Silvio Migliori
Summary: This paper introduces Crescoware, a container-based gateway for HPC/AI applications in the ENEAGRID infrastructure. Crescoware offers various features such as a collaborative catalog of Singularity containers, a workspace for creating new containers, and a web-based SSH client. By migrating workloads to Singularity containers, users can perform container operations in a visual environment, eliminating the need for complex command-line operations.
INTELLIGENT COMPUTING, VOL 1
(2022)