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Recent Advances in Antiviral Drugs Discovery

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 21181

Special Issue Editors

Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
Interests: chemical biology; medicinal chemistry; organic chemistry; drug design; HIV; integrase
Special Issues, Collections and Topics in MDPI journals
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
Interests: bioorganic and medicinal chemistry; peptide and peptide mimetic chemistry; inhibitors of phospho-dependent protein-protein interactions (PPIs); HIV integrase inhibitors; antibody-drug conjugates (ADCs); protein-tyrosine phosphatase inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human immunodeficiency virus type 1 (HIV-1) is the causative agent for acquired immunodeficiency syndrome (AIDS). This is a potentially life-threatening chronic disease that represents a major global public health crisis. Since the start of the AIDS pandemic, approximately 80 million people have been infected with HIV-1, and more than 30 million people have died of AIDS-related diseases. Approximately 40 million people are currently living with HIV infection. As a retrovirus, HIV encodes three key enzymes (reverse transcriptase (RT), integrase (IN), and protease (PR)) that are essential for viral replication. These enzymes catalyze reverse transcription of the viral RNA, integration of the resulting complementary DNA into the host genome, and proteolytic processing of the transcribed viral protein. Drugs that target these three enzymes are widely used in combination with antiretroviral therapies (cARTs) that have dramatically improved patient outcomes. The HIV-1 life cycle also entails additional key steps that are essential for viral replication. These steps include binding to cell surface proteins, fusion with the cell membrane, and viral assembly and budding. These processes also represent potential targets for therapeutic development. However, the extremely high mutation rate of HIV-1 means that drug-resistant variants are continually emerging against existing therapeutics. This makes it imperative to continue developing new and more potent antiviral compounds.

This Special Issue of Molecules is dedicated to bringing together research articles and reviews in the area of antiviral agent discovery and development related to HIV and more generally to antiviral therapeutics.

Dr. Xue Zhi Zhao
Dr. Terrence R. Burke
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antiviral
  • antiretroviral
  • drug resistance
  • drug design
  • antiviral small molecule
  • antiviral peptide
  • mutant

Published Papers (12 papers)

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Research

Jump to: Review

22 pages, 2158 KiB  
Article
Broad-Spectrum, Potent, and Durable Ceria Nanoparticles Inactivate RNA Virus Infectivity by Targeting Virion Surfaces and Disrupting Virus–Receptor Interactions
by Candace R. Fox, Kritika Kedarinath, Craig J. Neal, Jeremy Sheiber, Elayaraja Kolanthai, Udit Kumar, Christina Drake, Sudipta Seal and Griffith D. Parks
Molecules 2023, 28(13), 5190; https://doi.org/10.3390/molecules28135190 - 04 Jul 2023
Cited by 3 | Viewed by 1407
Abstract
There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce3+ ↔ Ce4+) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior [...] Read more.
There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce3+ ↔ Ce4+) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2. Treatment of human respiratory viruses, coronavirus OC43 and parainfluenza virus type 5 (PIV5) with AgCNP1 and 2, respectively, prevented virus interactions with host cell receptors and resulted in virion aggregation. Rhinovirus 14 (RV14) mutants were selected to be resistant to inactivation by AgCNP2. Sequence analysis of the resistant virus genomes predicted two amino acid changes in surface-located residues D91V and F177L within capsid protein VP1. Consistent with the regenerative properties of CNPs, surface-applied AgCNP1 and 2 inactivated a wide range of structurally diverse viruses, including enveloped (OC43, SARS-CoV-2, and PIV5) and non-enveloped RNA viruses (RV14 and feline calicivirus; FCV). Remarkably, a single application of AgCNP1 and 2 potently inactivated up to four sequential rounds of virus challenge. Our results show broad-spectrum and long-lasting anti-viral activity of AgCNP nanoparticles, due to targeting of viral surface proteins to disrupt interactions with cellular receptors. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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12 pages, 609 KiB  
Article
Cyclopentenylcytosine (CPE-C): In Vitro and In Vivo Evaluation as an Antiviral against Adenoviral Ocular Infections
by Eric G. Romanowski, Kathleen A. Yates and Y. Jerold Gordon
Molecules 2023, 28(13), 5078; https://doi.org/10.3390/molecules28135078 - 29 Jun 2023
Viewed by 787
Abstract
Adenoviruses are the major cause of ocular viral infections worldwide. Currently, there is no approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral that has demonstrated activity against more than 20 viruses. The goals of the current study were to [...] Read more.
Adenoviruses are the major cause of ocular viral infections worldwide. Currently, there is no approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral that has demonstrated activity against more than 20 viruses. The goals of the current study were to determine the in vitro and in vivo antiviral activity of CPE-C as well as its ocular toxicity. Antiviral activity was evaluated in vitro using standard plaque reduction assays to determine the 50% effective concentrations (EC50s) and in vivo in the Ad5/NZW rabbit ocular replication model. Ocular toxicity was determined in uninfected rabbit eyes following topical ocular application. The in vitro EC50s for CPE-C ranged from 0.03 to 0.059 μg/mL for nine adenovirus types that commonly infect the eye. Ocular toxicity testing determined CPE-C to be non-irritating or practically non-irritating by Draize scoring. In vivo, 3% CPE-C topically administered 4X or 2X daily for 7 days to adenovirus-infected eyes demonstrated effective antiviral activity compared with the negative control and comparable antiviral activity to the positive control, 0.5% cidofovir, topically administered twice daily for 7 days. We conclude CPE-C was relatively non-toxic to rabbit eyes and demonstrated potent anti-adenoviral activity in vitro and in vivo. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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22 pages, 2169 KiB  
Article
Synergy of Small Antiviral Molecules on a Black-Phosphorus Nanocarrier: Machine Learning and Quantum Chemical Simulation Insights
by Slimane Laref, Fouzi Harrou, Bin Wang, Ying Sun, Amel Laref, Taous-Meriem Laleg-Kirati, Takashi Gojobori and Xin Gao
Molecules 2023, 28(8), 3521; https://doi.org/10.3390/molecules28083521 - 17 Apr 2023
Viewed by 1256
Abstract
Favipiravir (FP) and Ebselen (EB) belong to a broad range of antiviral drugs that have shown active potential as medications against many viruses. Employing molecular dynamics simulations and machine learning (ML) combined with van der Waals density functional theory, we have uncovered the [...] Read more.
Favipiravir (FP) and Ebselen (EB) belong to a broad range of antiviral drugs that have shown active potential as medications against many viruses. Employing molecular dynamics simulations and machine learning (ML) combined with van der Waals density functional theory, we have uncovered the binding characteristics of these two antiviral drugs on a phosphorene nanocarrier. Herein, by using four different machine learning models (i.e., Bagged Trees, Gaussian Process Regression (GPR), Support Vector Regression (SVR), and Regression Trees (RT)), the Hamiltonian and the interaction energy of antiviral molecules in a phosphorene monolayer are trained in an appropriate way. However, training efficient and accurate models for approximating the density functional theory (DFT) is the final step in using ML to aid in the design of new drugs. To improve the prediction accuracy, the Bayesian optimization approach has been employed to optimize the GPR, SVR, RT, and BT models. Results revealed that the GPR model obtained superior prediction performance with an R2 of 0.9649, indicating that it can explain 96.49% of the data’s variability. Then, by means of DFT calculations, we examine the interaction characteristics and thermodynamic properties in a vacuum and a continuum solvent interface. These results illustrate that the hybrid drug is an enabled, functionalized 2D complex with vigorous thermostability. The change in Gibbs free energy at different surface charges and temperatures implies that the FP and EB molecules are allowed to adsorb from the gas phase onto the 2D monolayer at different pH conditions and high temperatures. The results reveal a valuable antiviral drug therapy loaded by 2D biomaterials that may possibly open a new way of auto-treating different diseases, such as SARS-CoV, in primary terms. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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16 pages, 3015 KiB  
Article
Anti-SARS-CoV-2 Activity and Cytotoxicity of Amaryllidaceae Alkaloids from Hymenocallis littoralis
by Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Tom Vermeyen, Aliou M. Baldé, Wouter A. Herrebout, Johan Neyts, Christophe Pannecouque, Luc Pieters and Emmy Tuenter
Molecules 2023, 28(7), 3222; https://doi.org/10.3390/molecules28073222 - 04 Apr 2023
Cited by 6 | Viewed by 1653
Abstract
The Amaryllidaceae species are well-known as a rich source of bioactive compounds in nature. Although Hymenocallis littoralis has been studied for decades, its polar components were rarely explored. The current phytochemical investigation of Amaryllidaceae alkaloids from H. littoralis led to the identification of [...] Read more.
The Amaryllidaceae species are well-known as a rich source of bioactive compounds in nature. Although Hymenocallis littoralis has been studied for decades, its polar components were rarely explored. The current phytochemical investigation of Amaryllidaceae alkaloids from H. littoralis led to the identification of three previously undescribed compounds: O-demethyl-norlycoramine (1), (−)-2-epi-pseudolycorine (2) and (+)-2-epi-pseudolycorine (3), together with eight known compounds: 6α-hydroxyhippeastidine (4), 6β-hydroxyhippeastidine (5), lycorine (6), 2-epi-lycorine (7), zephyranthine (8), ungeremine (9), pancratistatin (10) and 9-O-demethyl-7-O-methyllycorenine (11). Among the eight previously reported compounds, five were isolated from H. littoralis for the first time (compounds 4, 5, 7, 8, and 9). Compounds 1, 4, 5, 7, 8, and 11 exhibited weak anti-SARS-CoV-2 activity (EC50 = 40–77 µM) at non-cytotoxic concentrations. Assessment of cytotoxicity on the Vero-E6 cell line revealed lycorine and pancratistatin as cytotoxic substances with CC50 values of 1.2 µM and 0.13 µM, respectively. The preliminary structure-activity relationship for the lycorine-type alkaloids in this study was further investigated, and as a result ring C appears to play a crucial role in their anti-SARS-CoV-2 activity. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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15 pages, 2828 KiB  
Article
A Practical Approach to Bicyclic Carbamoyl Pyridones with Application to the Synthesis of HIV-1 Integrase Strand Transfer Inhibitors
by Pankaj S. Mahajan, Steven J. Smith, Stephen H. Hughes, Xuezhi Zhao and Terrence R. Burke, Jr.
Molecules 2023, 28(3), 1428; https://doi.org/10.3390/molecules28031428 - 02 Feb 2023
Cited by 4 | Viewed by 1488
Abstract
An efficient one-pot synthetic method has been developed for the preparation of bicyclic carbamoyl pyridones from the known common intermediate methyl 5-((2,4-difluorobenzyl)carbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate (8). The scalable protocol is facile and employs readily available reagents, needing only a single purification as the final [...] Read more.
An efficient one-pot synthetic method has been developed for the preparation of bicyclic carbamoyl pyridones from the known common intermediate methyl 5-((2,4-difluorobenzyl)carbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate (8). The scalable protocol is facile and employs readily available reagents, needing only a single purification as the final step. The utility of the approach was demonstrated by preparing a library of HIV-1 integrase strand transfer inhibitors (INSTIs) that differ by the presence or absence of a double bond in the B-ring of the bicyclic carbamoyl pyridines 6 and 7. Several of the analogs show good antiviral potencies in single-round HIV-1 replication antiviral assays and show no cytotoxicity in cell culture assays. In general, the compounds with a B-ring double bond have higher antiviral potencies than their saturated congeners. Our methodology should be applicable to the synthesis of a range of new metal-chelating analogs. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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11 pages, 918 KiB  
Communication
Privileged Scaffold Decoration for the Identification of the First Trisubstituted Triazine with Anti-SARS-CoV-2 Activity
by Silvia Cesarini, Ilaria Vicenti, Federica Poggialini, Massimiliano Secchi, Federica Giammarino, Ilenia Varasi, Camilla Lodola, Maurizio Zazzi, Elena Dreassi, Giovanni Maga, Lorenzo Botta and Raffaele Saladino
Molecules 2022, 27(24), 8829; https://doi.org/10.3390/molecules27248829 - 12 Dec 2022
Cited by 4 | Viewed by 1562
Abstract
Current therapy against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are based on the use of Remdesivir 1, Molnupiravir 2, and the recently identified Nirmatrelvir 3. Unfortunately, these three drugs showed some limitations regarding potency and possible drug–drug interactions. [...] Read more.
Current therapy against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are based on the use of Remdesivir 1, Molnupiravir 2, and the recently identified Nirmatrelvir 3. Unfortunately, these three drugs showed some limitations regarding potency and possible drug–drug interactions. A series of derivatives coming from a decoration approach of the privileged scaffold s-triazines were synthesized and evaluated against SAR-CoV-2. One derivative emerged as the hit of the series for its micromolar antiviral activity and low cytotoxicity. Mode of action and pharmacokinetic in vitro preliminary studies further confirm the role as candidates for a future optimization campaign of the most active derivative identified with this work. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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14 pages, 3048 KiB  
Article
A Comprehensive In Silico Study of New Metabolites from Heteroxenia fuscescens with SARS-CoV-2 Inhibitory Activity
by Fahd M. Abdelkarem, Alaa M. Nafady, Ahmed E. Allam, Mahmoud A. H. Mostafa, Rwaida A. Al Haidari, Heba Ali Hassan, Magdi E. A. Zaki, Hamdy K. Assaf, Mohamed R. Kamel, Sabry A. H. Zidan, Ahmed M. Sayed and Kuniyoshi Shimizu
Molecules 2022, 27(21), 7369; https://doi.org/10.3390/molecules27217369 - 29 Oct 2022
Cited by 1 | Viewed by 1463
Abstract
Chemical investigation of the total extract of the Egyptian soft coral Heteroxenia fuscescens, led to the isolation of eight compounds, including two new metabolites, sesquiterpene fusceterpene A (1) and a sterol fuscesterol A (4), along with six known [...] Read more.
Chemical investigation of the total extract of the Egyptian soft coral Heteroxenia fuscescens, led to the isolation of eight compounds, including two new metabolites, sesquiterpene fusceterpene A (1) and a sterol fuscesterol A (4), along with six known compounds. The structures of 18 were elucidated via intensive studies of their 1D, 2D-NMR, and HR-MS analyses, as well as a comparison of their spectral data with those mentioned in the literature. Subsequent comprehensive in-silico-based investigations against almost all viral proteins, including those of the new variants, e.g., Omicron, revealed the most probable target for these isolated compounds, which was found to be Mpro. Additionally, the dynamic modes of interaction of the putatively active compounds were highlighted, depending on 50-ns-long MDS. In conclusion, the structural information provided in the current investigation highlights the antiviral potential of H. fuscescens metabolites with 3β,5α,6β-trihydroxy steroids with different nuclei against SARS-CoV-2, including newly widespread variants. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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14 pages, 2820 KiB  
Article
Molecular and Structural Analysis of Specific Mutations from Saudi Isolates of SARS-CoV-2 RNA-Dependent RNA Polymerase and their Implications on Protein Structure and Drug–Protein Binding
by Mubarak A. Alamri, Muhammad Tahir ul Qamar, Alhumaidi B. Alabbas, Safar M. Alqahtani, Manal A. Alossaimi, Sikandar Azam, Muhammad Harris Hashmi and Muhammad Shahid Riaz Rajoka
Molecules 2022, 27(19), 6475; https://doi.org/10.3390/molecules27196475 - 01 Oct 2022
Cited by 7 | Viewed by 1621
Abstract
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has stressed the global health system to a significant level, which has not only resulted in high morbidity and mortality but also poses a threat for future pandemics. This situation warrants efforts [...] Read more.
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has stressed the global health system to a significant level, which has not only resulted in high morbidity and mortality but also poses a threat for future pandemics. This situation warrants efforts to develop novel therapeutics to manage SARS-CoV-2 in specific and other emerging viruses in general. This study focuses on SARS-CoV2 RNA-dependent RNA polymerase (RdRp) mutations collected from Saudi Arabia and their impact on protein structure and function. The Saudi SARS-CoV-2 RdRp sequences were compared with the reference Wuhan, China RdRp using a variety of computational and biophysics-based approaches. The results revealed that three mutations—A97V, P323I and Y606C—may affect protein stability, and hence the relationship of protein structure to function. The apo wild RdRp is more dynamically stable with compact secondary structure elements compared to the mutants. Further, the wild type showed stable conformational dynamics and interaction network to remdesivir. The net binding energy of wild-type RdRp with remdesivir is -50.76 kcal/mol, which is more stable than the mutants. The findings of the current study might deliver useful information regarding therapeutic development against the mutant RdRp, which may further furnish our understanding of SARS-CoV-2 biology. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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21 pages, 5612 KiB  
Article
Zika Virus Inhibitors Based on a 1,3-Disubstituted 1H-Pyrazolo[3,4-d]pyrimidine-amine Scaffold
by Eunkyung Jung, Ruben Soto-Acosta, Robert J. Geraghty and Liqiang Chen
Molecules 2022, 27(18), 6109; https://doi.org/10.3390/molecules27186109 - 19 Sep 2022
Cited by 3 | Viewed by 1291
Abstract
To search for Zika virus (ZIKV) antivirals, we have further explored previously reported 7H-pyrrolo[2,3-d]pyrimidines by examining an alternative substitution pattern of their central scaffold, leading to compound 5 with low micromolar antiviral activity. To circumvent the synthetic difficulties associated [...] Read more.
To search for Zika virus (ZIKV) antivirals, we have further explored previously reported 7H-pyrrolo[2,3-d]pyrimidines by examining an alternative substitution pattern of their central scaffold, leading to compound 5 with low micromolar antiviral activity. To circumvent the synthetic difficulties associated with compound 5, we have exploited a 1H-pyrazolo[3,4-d]pyrimidine scaffold and performed structure-activity relationship studies on its peripheral rings A and B. While ring B is less sensitive to structural modifications, an electron-withdrawing group at the para position of ring A is preferred for enhanced antiviral activity. Overall, we have not only discovered an alternative substitution pattern centered on a 1H-pyrazolo[3,4-d]pyrimidine scaffold but also generated anti-ZIKV compounds including 6 and 13, which possess low micromolar antiviral activity and relatively low cytotoxicity. These compounds represent new chemotypes that will be further optimized in our continued efforts to discover anti-ZIKV agents. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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13 pages, 2563 KiB  
Article
Targeting the Integrated Stress Response Kinase GCN2 to Modulate Retroviral Integration
by Chloé Torres, Asja Garling, Saïd Taouji, Christina Calmels, Marie-Line Andreola and Mathieu Métifiot
Molecules 2021, 26(17), 5423; https://doi.org/10.3390/molecules26175423 - 06 Sep 2021
Cited by 3 | Viewed by 2534
Abstract
Multiple viral targets are now available in the clinic to fight HIV infection. Even if this targeted therapy is highly effective at suppressing viral replication, caregivers are facing growing therapeutic failures in patients due to resistance, with or without treatment-adherence glitches. Accordingly, it [...] Read more.
Multiple viral targets are now available in the clinic to fight HIV infection. Even if this targeted therapy is highly effective at suppressing viral replication, caregivers are facing growing therapeutic failures in patients due to resistance, with or without treatment-adherence glitches. Accordingly, it is important to better understand how HIV and other retroviruses replicate in order to propose alternative antiviral strategies. Recent studies have shown that multiple cellular factors are implicated during the integration step and, more specifically, that integrase can be regulated through post-translational modifications. We have shown that integrase is phosphorylated by GCN2, a cellular protein kinase of the integrated stress response, leading to a restriction of HIV replication. In addition, we found that this mechanism is conserved among other retroviruses. Accordingly, we developed an in vitro interaction assay, based on the AlphaLISA technology, to monitor the integrase-GCN2 interaction. From an initial library of 133 FDA-approved molecules, we identified nine compounds that either inhibited or stimulated the interaction between GCN2 and HIV integrase. In vitro characterization of these nine hits validated this pilot screen and demonstrated that the GCN2-integrase interaction could be a viable solution for targeting integrase out of its active site. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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Review

Jump to: Research

16 pages, 586 KiB  
Review
Anti-COVID-19 Potential of Ellagic Acid and Polyphenols of Punica granatum L.
by Ralitza Alexova, Simona Alexandrova, Stela Dragomanova, Reni Kalfin, Ayten Solak, Sidharth Mehan, Maria Cristina Petralia, Paolo Fagone, Katia Mangano, Ferdinando Nicoletti and Lyubka Tancheva
Molecules 2023, 28(9), 3772; https://doi.org/10.3390/molecules28093772 - 27 Apr 2023
Cited by 6 | Viewed by 1934
Abstract
Pomegranate (Punica granatum L.) is a rich source of polyphenols, including ellagitannins and ellagic acid. The plant is used in traditional medicine, and its purified components can provide anti-inflammatory and antioxidant activity and support of host defenses during viral infection and recovery [...] Read more.
Pomegranate (Punica granatum L.) is a rich source of polyphenols, including ellagitannins and ellagic acid. The plant is used in traditional medicine, and its purified components can provide anti-inflammatory and antioxidant activity and support of host defenses during viral infection and recovery from disease. Current data show that pomegranate polyphenol extract and its ellagitannin components and metabolites exert their beneficial effects by controlling immune cell infiltration, regulating the cytokine secretion and reactive oxygen and nitrogen species production, and by modulating the activity of the NFκB pathway. In vitro, pomegranate extracts and ellagitannins interact with and inhibit the infectivity of a range of viruses, including SARS-CoV-2. In silico docking studies show that ellagitannins bind to several SARS-CoV-2 and human proteins, including a number of proteases. This warrants further exploration of polyphenol–viral and polyphenol–host interactions in in vitro and in vivo studies. Pomegranate extracts, ellagitannins and ellagic acid are promising agents to target the SARS-CoV-2 virus and to restrict the host inflammatory response to viral infections, as well as to supplement the depleted host antioxidant levels during the stage of recovery from COVID-19. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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16 pages, 1200 KiB  
Review
The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses
by Beata Pająk, Rafał Zieliński, John Tyler Manning, Stanislava Matejin, Slobodan Paessler, Izabela Fokt, Mark R. Emmett and Waldemar Priebe
Molecules 2022, 27(18), 5928; https://doi.org/10.3390/molecules27185928 - 12 Sep 2022
Cited by 12 | Viewed by 3317
Abstract
Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to the infection. Among metabolic changes, the most prominent is the upregulated glycolysis process as the main pathway of glucose utilization. Glycolysis activation is [...] Read more.
Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to the infection. Among metabolic changes, the most prominent is the upregulated glycolysis process as the main pathway of glucose utilization. Glycolysis activation is a common mechanism of cell adaptation to several viral infections, including noroviruses, rhinoviruses, influenza virus, Zika virus, cytomegalovirus, coronaviruses and others. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Glycolysis inhibitors, especially 2-deoxy-D-glucose (2-DG), have been intensively studied as antiviral agents. However, 2-DG’s poor pharmacokinetic properties limit its wide clinical application. Herein, we discuss the potential of 2-DG and its novel analogs as potent promising antiviral drugs with special emphasis on targeted intracellular processes. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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