Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
Antiviral Compounds in Medicinal Plants
share announcement

Antiviral Compounds in Medicinal Plants

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 71824

Special Issue Editor

Dr. Daniela De Vita

E-Mail Website
Guest Editor
Department of Environmental Biology, Sapienza University of Rome, Rome, Italy
Interests: medicinal plants; alkaloids; phytochemistry; HPLC; LC-MS; antiviral agents; antifungal agents; anticancer agents; Alzheimer’s disease; cholinesterases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Plants have always been considered as a source of molecules useful for humans and still are helpful in the discovery of new therapeutic agents. To date, a wide variety of extracts and/or natural compounds isolated from plants have been extensively evaluated against infections caused by viruses that can affect human health. Due to the emergence of drug-resistance or lack of vaccines, the search for new antiviral agents is needed.    Authors are invited to submit original research articles, reviews, and short communications exploring recent advances in this field ranging from basic science to clinical studies. Topics include but are not limited to in vitro and in vivo evaluation of antiviral activities of plant extracts or compounds isolated from natural sources.

Dr. Daniela De Vita
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 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 agents
  • viruses
  • medicinal plants
  • phytochemicals
  • natural compounds

Published Papers (19 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

9 pages, 1272 KiB  
Article
Kaempferol Interferes with Varicella-Zoster Virus Replication in Human Foreskin Fibroblasts
by Subin Park, Na-Eun Kim, Bang Ju Park, Hak Cheol Kwon and Yoon-Jae Song
Pharmaceuticals 2022, 15(12), 1582; https://doi.org/10.3390/ph15121582 - 19 Dec 2022
Cited by 7 | Viewed by 1490
Abstract
Kaempferol, a natural flavonoid abundantly found in plants, is known to have pharmacological properties, such as anti-inflammatory and anti-cancer effects. In this study, we investigated the antiviral effects of kaempferol against a varicella-zoster virus (VZV) clinical isolate in vitro. We found that kaempferol [...] Read more.
Kaempferol, a natural flavonoid abundantly found in plants, is known to have pharmacological properties, such as anti-inflammatory and anti-cancer effects. In this study, we investigated the antiviral effects of kaempferol against a varicella-zoster virus (VZV) clinical isolate in vitro. We found that kaempferol significantly inhibited VZV replication without exhibiting cytotoxicity. Kaempferol exerted its antiviral effect at a similar stage of the VZV life cycle as acyclovir, which inhibits VZV DNA replication. Taken together, our results suggest that kaempferol inhibits VZV infection by blocking the DNA replication stage in the viral life cycle. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

16 pages, 2625 KiB  
Article
In Vitro Anti-Influenza Virus Activity of Non-Polar Primula veris subsp. veris Extract
by Aristides G. Eliopoulos, Apostolis Angelis, Anastasia Liakakou and Leandros A. Skaltsounis
Pharmaceuticals 2022, 15(12), 1513; https://doi.org/10.3390/ph15121513 - 05 Dec 2022
Cited by 2 | Viewed by 1696
Abstract
Medicinal plants have long been recognized as a tremendous source of candidate compounds for the development of pharmaceuticals, including anti-viral agents. Herein, we report the identification of anti-influenza virus activity in non-polar Primula veris L. subsp. veris extracts. We show that P. veris [...] Read more.
Medicinal plants have long been recognized as a tremendous source of candidate compounds for the development of pharmaceuticals, including anti-viral agents. Herein, we report the identification of anti-influenza virus activity in non-polar Primula veris L. subsp. veris extracts. We show that P. veris subsp. veris flower extracts, obtained using supercritical fluid or ultrasound-based extraction, possess virucidal/virus inactivation properties and confer prophylactic and therapeutic effects against influenza virus-induced cytolysis in vitro. By GC-MS and UPLC-HRMS analysis of non-polar P. veris subsp. veris extracts we identified terpenes, flavones, tocopherols, and other classes of phytochemicals with known or putative anti-influenza properties. In silico prediction of cellular functions and molecular pathways affected by these phytochemicals suggests putative effects on signal transduction, inflammasome, and cell death pathways that are relevant to influenza virus pathogenesis. Combining P. veris subsp. veris with extracts of medicinal plants with proven anti-influenza activity such as Echinacea purpurea (L.) Moench and Cistus creticus L. subsp. creticus achieves an impressive protective effect against infection by influenza virus H1N1 in vitro and reduced progeny virus production by infected cells. Collectively, these findings uncover a previously uncharted biological property of non-polar P. veris flower extracts that warrants further studies to assess clinical efficacy. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

15 pages, 2202 KiB  
Article
Antiviral Effect of Stenocline ericoides DC. and Stenocline inuloides DC., Two Flavonoid-Rich Endemic Plants from Madagascar, against Dengue and Zika Viruses
by Fenia D. Ramiharimanana, Juliano G. Haddad, Maminiaina A. Andrianavalonirina, Cécile Apel, Florent Olivon, Nicolas Diotel, Philippe Desprès, Voahangy Vestalys Ramanandraibe and Chaker El Kalamouni
Pharmaceuticals 2022, 15(12), 1500; https://doi.org/10.3390/ph15121500 - 30 Nov 2022
Cited by 1 | Viewed by 1638
Abstract
Dengue and Zika viruses are identified as the most medically important arthropod-borne viral pathogens. Over the past 20 years, the global dengue incidence has dramatically increased with epidemics of severe dengue where the case fatality rate can reach up to 20% in untreated [...] Read more.
Dengue and Zika viruses are identified as the most medically important arthropod-borne viral pathogens. Over the past 20 years, the global dengue incidence has dramatically increased with epidemics of severe dengue where the case fatality rate can reach up to 20% in untreated patients. The association between Zika virus infection and severe congenital anomalies was first reported in 2015. Today no specific antiviral therapies are available for dengue and Zika virus infections, accentuating the need of adapted antiviral strategies based on medicinal plant drug discovery. Plants are a potential source of antiviral phytocompounds which act primarily by blocking virus entry in the host-cell. In the present study, we evaluated whether crude extracts from Stenocline ericoides DC. and Stenocline inuloides DC., two endemic plants from Madagascar, may have antiviral effects against dengue and Zika viruses. We showed that S. ericoides has virucidal action whereas S. inuloides inhibits the early steps of virus infection with a non-cytotoxic effect in human cells. The administration of S. ericoides and S. inuloides extracts in zebrafish had no effect on the behavior of animals at the active doses against dengue and Zika viruses, suggesting the absence of adverse effects at these doses. LC-HRMS2 and molecular networking analyses revealed the richness of these two plants in polyphenols and flavonoid with the presence of clusters of phytocompounds specific to each Stenocline species. Consequently, S. ericoides and S. inuloides represent potential sources for natural and safe antiviral phytocompounds against flaviviruses of medical concern. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

14 pages, 6489 KiB  
Article
Effect of Structural Differences in Naringenin, Prenylated Naringenin, and Their Derivatives on the Anti-Influenza Virus Activity and Cellular Uptake of Their Flavanones
by Ryosuke Morimoto, Chiaki Matsubara, Akari Hanada, Yuta Omoe, Tokutaro Ogata and Yuji Isegawa
Pharmaceuticals 2022, 15(12), 1480; https://doi.org/10.3390/ph15121480 - 28 Nov 2022
Cited by 5 | Viewed by 1535
Abstract
Vaccines and antiviral drugs are widely used to treat influenza infection. However, they cannot rapidly respond to drug-resistant viruses. Therefore, new anti-influenza virus strategies are required. Naringenin is a flavonoid with potential for new antiviral strategies. In this study, we evaluated the antiviral [...] Read more.
Vaccines and antiviral drugs are widely used to treat influenza infection. However, they cannot rapidly respond to drug-resistant viruses. Therefore, new anti-influenza virus strategies are required. Naringenin is a flavonoid with potential for new antiviral strategies. In this study, we evaluated the antiviral effects of naringenin derivatives and examined the relationship between their cellular uptake and antiviral effects. Madin–Darby canine kidney (MDCK) cells were infected with the A/PR/8/34 strain and exposed to the compound-containing medium for 24 h. The amount of virus in the supernatant was calculated using focus-forming reduction assay. Antiviral activity was evaluated using IC50 and CC50 values. Cells were exposed to a constant concentration of naringenin or prenylated naringenin, and intracellular uptake and distribution were evaluated using a fluorescence microscope. Prenylated naringenin showed strong anti-influenza virus effects, and the amount of intracellular uptake was revealed by the strong intracellular fluorescence. In addition, intracellular distribution differed depending on the position of the prenyl group. The steric factor of naringenin is deeply involved in influenza A virus activity, and prenyl groups are desirable. Furthermore, the prenyl group affects cellular affinity, and the uptake mechanism differs depending on its position. These results provide important information on antiviral strategies. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

15 pages, 2005 KiB  
Article
Novel Aporphine- and Proaporphine–Clerodane Hybrids Identified from the Barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula with Strong Anti-DENV2 Activity
by I-Wen Lo, Geng-You Liao, Jin-Ching Lee, Chi-I Chang, Yang-Chang Wu, Yen-Yu Chen, Shang-Pin Liu, Huey-Jen Su, Chih-I Liu, Chia-Yi Kuo, Zheng-Yu Lin, Tsung-Lin Li, Yun-Sheng Lin and Chia-Ching Liaw
Pharmaceuticals 2022, 15(10), 1218; https://doi.org/10.3390/ph15101218 - 30 Sep 2022
Cited by 4 | Viewed by 1684
Abstract
Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two [...] Read more.
Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C–C or N–C covalent linkage. Here, we report four structurally attractive diterpene–alkaloid conjugates polyalongarins A–D (1–4), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula. In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine the chemical structures and stereo-configurations of 1. Compounds 1–4 were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC50 (2.8–6.4 μM) and CC50 values (50.4–200 μM). The inhibitory mechanism of 1–4 on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of 1–4 and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane–aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

17 pages, 6694 KiB  
Article
Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators
by Lorenza Fagnani, Lisaurora Nazzicone, Pierangelo Bellio, Nicola Franceschini, Donatella Tondi, Andrea Verri, Sabrina Petricca, Roberto Iorio, Gianfranco Amicosante, Mariagrazia Perilli and Giuseppe Celenza
Pharmaceuticals 2022, 15(6), 714; https://doi.org/10.3390/ph15060714 - 04 Jun 2022
Cited by 2 | Viewed by 2080
Abstract
The study investigated the inhibitory activity of protocetraric and salazinic acids against SARS-CoV-2 3CLpro. The kinetic parameters were determined by microtiter plate-reading fluorimeter using a fluorogenic substrate. The cytotoxic activity was tested on murine Sertoli TM4 cells. In silico analysis was [...] Read more.
The study investigated the inhibitory activity of protocetraric and salazinic acids against SARS-CoV-2 3CLpro. The kinetic parameters were determined by microtiter plate-reading fluorimeter using a fluorogenic substrate. The cytotoxic activity was tested on murine Sertoli TM4 cells. In silico analysis was performed to ascertain the nature of the binding with the 3CLpro. The compounds are slow-binding inactivators of 3CLpro with a Ki of 3.95 μM and 3.77 μM for protocetraric and salazinic acid, respectively, and inhibitory efficiency kinact/Ki at about 3 × 10−5 s−1µM−1. The mechanism of inhibition shows that both compounds act as competitive inhibitors with the formation of a stable covalent adduct. The viability assay on epithelial cells revealed that none of them shows cytotoxicity up to 80 μM, which is well below the Ki values. By molecular modelling, we predicted that the catalytic Cys145 makes a nucleophilic attack on the carbonyl carbon of the cyclic ester common to both inhibitors, forming a stably acyl-enzyme complex. The computational and kinetic analyses confirm the formation of a stable acyl-enzyme complex with 3CLpro. The results obtained enrich the knowledge of the already numerous biological activities exhibited by lichen secondary metabolites, paving the way for developing promising scaffolds for the design of cysteine enzyme inhibitors. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

16 pages, 1889 KiB  
Article
Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L.
by Michał Ochnik, Dominika Franz, Maciej Sobczyński, Piotr Naporowski, Mariusz Banach, Beata Orzechowska and Marta Sochocka
Pharmaceuticals 2022, 15(5), 619; https://doi.org/10.3390/ph15050619 - 17 May 2022
Cited by 3 | Viewed by 2337
Abstract
Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with [...] Read more.
Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry. The aim of this study was to assess the in vitro antiviral ability of an originally designed double-standardized blend of extracts from Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L. (EAM-ESN) or separated extracts of A. melanocarpa (EAM) or S. nigra (ESN) against four human respiratory tract viruses: influenza A virus (A/H1N1), betacoronavirus-1 (HCoV-OC43) belonging to the same β-coronaviruses as the current pandemic SARS-CoV-2, human herpesvirus type 1 (HHV-1), and human adenovirus type 5 (HAdV-5). Antiviral assays (AVAs) were used to evaluate the antiviral activity of the plant extracts in a cell-present environment with extracts tested before, simultaneously, or after viral infection. The virus replication was assessed using the CPE scale or luminescent assay. The EAM-ESN blend strongly inhibited A/H1N1 replication as well as HCoV-OC43, while having a limited effect against HHV-1 and HAdV-5. This activity likely depends mostly on the presence of the extract of S. nigra. However, the EAM-ESN blend possesses more effective inhibitory activity toward virus replication than its constituent extracts. A post-infection mechanism of action of the EAM-ESN make this blend the most relevant for potential drugs and supportive treatments; thus, the EAM-ESN blend might be considered as a natural remedy in mild, seasonal respiratory viral infections. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

19 pages, 8738 KiB  
Article
In Silico and In Vitro Identification of Pan-Coronaviral Main Protease Inhibitors from a Large Natural Product Library
by Nasim Shahhamzehei, Sara Abdelfatah and Thomas Efferth
Pharmaceuticals 2022, 15(3), 308; https://doi.org/10.3390/ph15030308 - 03 Mar 2022
Cited by 24 | Viewed by 6265
Abstract
The main protease (Mpro or 3CLpro) in coronaviruses represents a promising specific drug target as it is essential for the cleavage of the virus polypeptide and has a unique cleavage site that does not exist in human host proteases. In [...] Read more.
The main protease (Mpro or 3CLpro) in coronaviruses represents a promising specific drug target as it is essential for the cleavage of the virus polypeptide and has a unique cleavage site that does not exist in human host proteases. In this study, we explored potential natural pan-coronavirus drugs using in vitro and in silico approaches and three coronavirus main proteases as treatment targets. The PyRx program was used to screen 39,442 natural-product-like compounds from the ZINC database and 121 preselected phytochemicals from medicinal plants with known antiviral activity. After assessment with Lipinski’s rule of five, molecular docking was performed for the top 33 compounds of both libraries. Enzymatic assays were applied for the top candidates from both in silico approaches to test their ability to inhibit SARS-CoV-2 Mpro. The four compounds (hypericin, rosmarinic acid, isorhamnetin, and luteolin) that most efficiently inhibited SARS-CoV-2 Mpro in vitro were further tested for their efficacy in inhibiting Mpro of SARS-CoV-1 and MERS-CoV. Microscale thermophoresis was performed to determine dissociation constant (Kd) values to validate the binding of these active compounds to recombinant Mpro proteins of SARS-CoV-2, SARS-CoV-1, and MERS-CoV. The cytotoxicity of hypericin, rosmarinic acid, isorhamnetin, and luteolin was assessed in human diploid MRC-5 lung fibroblasts using the resazurin cell viability assay to determine their therapeutic indices. Sequence alignment of Mpro of SARS-CoV-2 demonstrated 96.08%, 50.83%, 49.17%, 48.51%, 44.04%, and 41.06% similarity to Mpro of other human-pathogenic coronaviruses (SARS-CoV-1, MERS-CoV, HCoV-NL63, HCoV-OC43, HCoV-HKU1, and HCoV-229E, respectively). Molecular docking showed that 12 out of 121 compounds were bound to SARS-CoV-2 Mpro at the same binding site as the control inhibitor, GC376. Enzyme inhibition assays revealed that hypericin, rosmarinic acid, isorhamnetin, and luteolin inhibited Mpro of SARS-CoV-2, while hypericin and isorhamnetin inhibited Mpro of SARS-CoV-1; hypericin showed inhibitory effects toward Mpro of MERS-CoV. Microscale thermophoresis confirmed the binding of these compounds to Mpro with high affinity. Resazurin assays showed that rosmarinic acid and luteolin were not cytotoxic toward MRC-5 cells, whereas hypericin and isorhamnetin were slightly cytotoxic. We demonstrated that hypericin represents a potential novel pan-anti-coronaviral agent by binding to and inhibiting Mpro of several human-pathogenic coronaviruses. Moreover, isorhamnetin showed inhibitory effects toward SARS-CoV-2 and SARS-CoV-1 Mpro, indicating that this compound may have some pan-coronaviral potential. Luteolin had inhibitory effects against SARS-CoV-2 Mpro. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

14 pages, 2602 KiB  
Article
Antiviral Effects of Artemisinin and Its Derivatives against SARS-CoV-2 Main Protease: Computational Evidences and Interactions with ACE2 Allelic Variants
by Riadh Badraoui, Mongi Saoudi, Walid S. Hamadou, Salem Elkahoui, Arif J. Siddiqui, Jahoor M. Alam, Arshad Jamal, Mohd Adnan, Abdel M. E. Suliemen, Mousa M. Alreshidi, Dharmendra K. Yadav, Houcine Naïli and Hmed Ben-Nasr
Pharmaceuticals 2022, 15(2), 129; https://doi.org/10.3390/ph15020129 - 22 Jan 2022
Cited by 25 | Viewed by 4394
Abstract
Fighting against the emergent coronavirus disease (COVID-19) remains a big challenge at the front of the world communities. Recent research has outlined the potential of various medicinal herbs to counteract the infection. This study aimed to evaluate the interaction of artemisinin, a sesquiterpene [...] Read more.
Fighting against the emergent coronavirus disease (COVID-19) remains a big challenge at the front of the world communities. Recent research has outlined the potential of various medicinal herbs to counteract the infection. This study aimed to evaluate the interaction of artemisinin, a sesquiterpene lactone extracted from the Artemisia genus, and its derivatives with the SARS-CoV-2 main protease. To assess their potential use against COVID-19, the interactions of the main active principle of Artemisia with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) was investigated through in silico probing. Our results showed that artemesinin and its derivatives manifested good oral absorption and bioavailability scores (0.55). They potently bound to the Mpro site of action—specifically, to its Cys145 residue. The selected compounds established two to three conventional hydrogen bonds with binding affinities ranging between −5.2 and −8.1 kcal/mol. Furthermore, artemisinin interactions with angiotensin converting enzyme 2 (ACE2) were dependent on the ACE2 allelic variants. The best score was recorded with rs961360700. A molecular dynamic simulation showed sufficient stability of the artemisinin–Mpro complex on the trajectory of 100 ns simulation frame. These binding interactions, together with drug-likeness and pharmacokinetic findings, confirmed that artemisinin might inhibit Mpro activity and explain the ethnopharmacological use of the herb and its possible antiviral activity against SARS-CoV-2 infection inducing COVID-19. Nevertheless, it interacted differently with the various ACE2 allelic variants reported to bind with the SARS-CoV-2 spike protein. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

22 pages, 4943 KiB  
Article
Discovery of Novel Andrographolide Derivatives as Antiviral Inhibitors against Human Enterovirus A71
by Jie Kai Tan, Ran Chen, Regina Ching Hua Lee, Feng Li, Kun Dai, Guo-Chun Zhou and Justin Jang Hann Chu
Pharmaceuticals 2022, 15(2), 115; https://doi.org/10.3390/ph15020115 - 18 Jan 2022
Cited by 5 | Viewed by 3106
Abstract
Hand-foot-and-mouth disease (HFMD) caused by human enterovirus A71 (EV-A71) infection has been associated with severe neurological complications. With the lack of an internationally approved antiviral, coupled with a surge in outbreaks globally, EV-A71 has emerged as a neurotropic virus of high clinical importance. [...] Read more.
Hand-foot-and-mouth disease (HFMD) caused by human enterovirus A71 (EV-A71) infection has been associated with severe neurological complications. With the lack of an internationally approved antiviral, coupled with a surge in outbreaks globally, EV-A71 has emerged as a neurotropic virus of high clinical importance. Andrographolide has many pharmacological effects including antiviral activity and its derivative, andrographolide sulfonate, has been used in China clinically to treat EV-A71 infections. This study sought to identify novel andrographolide derivatives as EV-A71 inhibitors and elucidate their antiviral mode of action. Using an immunofluorescence-based phenotypic screen, we identified novel EV-A71 inhibitors from a 344-compound library of andrographolide derivatives and validated them with viral plaque assays. Among these hits, ZAF-47, a quinolinoxy-andrographolide, was selected for downstream mechanistic studies. It was found that ZAF-47 acts on EV-A71 post-entry stages and inhibits EV-A71 protein expression. Subsequent luciferase studies confirm that ZAF-47 targets EV-A71 genome RNA replication specifically. Unsuccessful attempts in generating resistant mutants led us to believe a host factor is likely to be involved which coincide with the finding that ZAF-47 exhibits broad-spectrum antiviral activity against other enteroviruses (CV-A16, CV-A6, Echo7, CV-B5, CV-A24 and EV-D68). Furthermore, ZAF-46 and ZAF-47, hits from the screen, were derivatives of the same series containing quinolinoxy and olefin modifications, suggesting that an andrographolide scaffold mounted with these unique moieties could be a potential anti-EV-A71/HFMD strategy. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

14 pages, 2490 KiB  
Article
Elucidating the Effects of Curcumin against Influenza Using In Silico and In Vitro Approaches
by Minjee Kim, Hanul Choi, Sumin Kim, Lin Woo Kang and Young Bong Kim
Pharmaceuticals 2021, 14(9), 880; https://doi.org/10.3390/ph14090880 - 30 Aug 2021
Cited by 6 | Viewed by 2881
Abstract
The influenza virus is a constantly evolving pathogen that challenges medical and public health systems. Traditionally, curcumin has been used to treat airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate common targets of curcumin and influenza infection and underlying mechanisms, we [...] Read more.
The influenza virus is a constantly evolving pathogen that challenges medical and public health systems. Traditionally, curcumin has been used to treat airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate common targets of curcumin and influenza infection and underlying mechanisms, we employed network pharmacology and molecular docking approaches and confirmed results using in vitro experiments. Biological targets of curcumin and influenza were collected, and potential targets were identified by constructing compound–disease target (C-D) and protein–protein interaction (PPI) networks. The ligand–target interaction was determined using the molecular docking method, and in vitro antiviral experiments and target confirmation were conducted to evaluate curcumin’s effects on influenza. Our network and pathway analyses implicated the four targets of AKT1, RELA, MAPK1, and TP53 that could be involved in the inhibitory effects of curcumin on influenza. The binding energy calculations of each ligand–target interaction in the molecular docking showed that curcumin bound to AKT1 with the highest affinity among the four targets. In vitro experiments, in which influenza virus-infected MDCK cells were pre-, co-, or post-treated with curcumin, confirmed curcumin’s prophylactic and therapeutic effects. Influenza virus induction increased the level of mRNA expression of AKT in MDCK cells, and the level was attenuated by curcumin treatment. Collectively, our findings identified potential targets of curcumin against influenza and suggest curcumin as a potential therapy for influenza infection. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

19 pages, 6772 KiB  
Article
Reynoutria Rhizomes as a Natural Source of SARS-CoV-2 Mpro Inhibitors–Molecular Docking and In Vitro Study
by Izabela Nawrot-Hadzik, Mikolaj Zmudzinski, Adam Matkowski, Robert Preissner, Małgorzata Kęsik-Brodacka, Jakub Hadzik, Marcin Drag and Renata Abel
Pharmaceuticals 2021, 14(8), 742; https://doi.org/10.3390/ph14080742 - 29 Jul 2021
Cited by 26 | Viewed by 6621
Abstract
More than a year has passed since the world began to fight the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the Coronavirus disease 2019 (COVID-19) pandemic, and still it spreads around the world, mutating at the same time. One of [...] Read more.
More than a year has passed since the world began to fight the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the Coronavirus disease 2019 (COVID-19) pandemic, and still it spreads around the world, mutating at the same time. One of the sources of compounds with potential antiviral activity is Traditional Chinese Medicinal (TCM) plants used in China in the supportive treatment of COVID-19. Reynoutria japonica is important part of the Shu Feng Jie Du Granule/Capsule-TCM herbal formula, recommended by China Food and Drug Administration (CFDA) for treatment of patients with H1N1- and H5N9-induced acute lung injury and is also used in China to treat COVID-19, mainly combined with other remedies. In our study, 25 compounds from rhizomes of R. japonica and Reynoutria sachalinensis (related species), were docked into the binding site of SARS-CoV-2 main protease. Next, 11 of them (vanicoside A, vanicoside B, resveratrol, piceid, emodin, epicatechin, epicatechin gallate, epigallocatechin gallate, procyanidin B2, procyanidin C1, procyanidin B2 3,3’-di-O-gallate) as well as extracts and fractions from rhizomes of R. japonica and R. sachalinensis were tested in vitro using a fluorescent peptide substrate. Among the tested phytochemicals the best results were achieved for vanicoside A and vanicoside B with moderate inhibition of SARS-CoV-2 Mpro, IC50 = 23.10 µM and 43.59 µM, respectively. The butanol fractions of plants showed the strongest inhibition of SARS-CoV-2 Mpro (IC50 = 4.031 µg/mL for R. sachalinensis and IC50 = 7.877 µg/mL for R. japonica). As the main constituents of butanol fractions, besides the phenylpropanoid disaccharide esters (e.g., vanicosides), are highly polymerized procyanidins, we suppose that they could be responsible for their strong inhibitory properties. As inhibition of SARS-CoV-2 main protease could prevent the replication of the virus our research provides data that may explain the beneficial effects of R. japonica on COVID-19 and identify the most active compounds worthy of more extensive research. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

22 pages, 3416 KiB  
Article
Bioactive Compounds from Euphorbia usambarica Pax. with HIV-1 Latency Reversal Activity
by Yu-Chi Tsai, Racheal A. Nell, Jonathan E. Buckendorf, Norbert Kúsz, Peter Waweru Mwangi, Róbert Berkecz, Dóra Rédei, Andrea Vasas, Adam M. Spivak and Judit Hohmann
Pharmaceuticals 2021, 14(7), 653; https://doi.org/10.3390/ph14070653 - 07 Jul 2021
Cited by 4 | Viewed by 2796
Abstract
Euphorbia usambarica is a traditional medicine used for gynecologic, endocrine, and urogenital illnesses in East Africa; however, its constituents and bioactivities have not been investigated. A variety of compounds isolated from Euphorbia species have been shown to have activity against latent HIV-1, the [...] Read more.
Euphorbia usambarica is a traditional medicine used for gynecologic, endocrine, and urogenital illnesses in East Africa; however, its constituents and bioactivities have not been investigated. A variety of compounds isolated from Euphorbia species have been shown to have activity against latent HIV-1, the major source of HIV-1 persistence despite antiretroviral therapy. We performed bioactivity-guided isolation to identify 15 new diterpenoids (1–9, 14–17, 19, and 20) along with 16 known compounds from E. usambarica with HIV-1 latency reversal activity. Euphordraculoate C (1) exhibits a rare 6/6/3-fused ring system with a 2-methyl-2-cyclopentenone moiety. Usambariphanes A (2) and B (3) display an unusual lactone ring constructed between C-17 and C-2 in the jatrophane structure. 4β-Crotignoid K (14) revealed a 250-fold improvement in latency reversal activity compared to crotignoid K (13), identifying that configuration at the C-4 of tigliane diterpenoids is critical to HIV-1 latency reversal activity. The primary mechanism of the active diterpenoids 12–14 and 21 for the HIV-1 latency reversal activity was activation of PKC, while lignans 26 and 27 that did not increase CD69 expression, suggesting a non-PKC mechanism. Accordingly, natural constituents from E. usambarica have the potential to contribute to the development of HIV-1 eradication strategies. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

19 pages, 1461 KiB  
Review
Pharmacological Potential of Flavonoids against Neurotropic Viruses
by Juliana Helena Castro e Silva, Jéssica Teles Souza, Clarissa Schitine, Aníbal de Freitas Santos Júnior, Eduardo Muniz Santana Bastos and Silvia Lima Costa
Pharmaceuticals 2022, 15(9), 1149; https://doi.org/10.3390/ph15091149 - 15 Sep 2022
Cited by 6 | Viewed by 2202
Abstract
Flavonoids are a group of natural compounds that have been described in the literature as having anti-inflammatory, antioxidant, and neuroprotective compounds. Although they are considered versatile molecules, little has been discussed about their antiviral activities for neurotropic viruses. Hence, the present study aimed [...] Read more.
Flavonoids are a group of natural compounds that have been described in the literature as having anti-inflammatory, antioxidant, and neuroprotective compounds. Although they are considered versatile molecules, little has been discussed about their antiviral activities for neurotropic viruses. Hence, the present study aimed to investigate the pharmacological potential of flavonoids in the face of viruses that can affect the central nervous system (CNS). We carried out research from 2011 to 2021 using the Pubmed platform. The following were excluded: articles not in the English language, letters to editors, review articles and papers that did not include any experimental or clinical tests, and papers that showed antiviral activities against viruses that do not infect human beings. The inclusion criteria were in silico predictions and preclinical pharmacological studies, in vitro, in vivo and ex vivo, and clinical studies with flavonoids, flavonoid fractions and extracts that were active against neurotropic viruses. The search resulted in 205 articles that were sorted per virus type and discussed, considering the most cited antiviral activities. Our investigation shows the latest relevant data about flavonoids that have presented a wide range of actions against viruses that affect the CNS, mainly influenza, hepatitis C and others, such as the coronavirus, enterovirus, and arbovirus. Considering that these molecules present well-known anti-inflammatory and neuroprotective activities, using flavonoids that have demonstrated both neuroprotective and antiviral effects could be viewed as an alternative for therapy in the course of CNS infections. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

20 pages, 1892 KiB  
Review
Immunomodulatory and Antiaging Mechanisms of Resveratrol, Rapamycin, and Metformin: Focus on mTOR and AMPK Signaling Networks
by Vincenzo Sorrenti, Francesca Benedetti, Alessandro Buriani, Stefano Fortinguerra, Giada Caudullo, Sergio Davinelli, Davide Zella and Giovanni Scapagnini
Pharmaceuticals 2022, 15(8), 912; https://doi.org/10.3390/ph15080912 - 23 Jul 2022
Cited by 18 | Viewed by 6320
Abstract
Aging results from the progressive dysregulation of several molecular pathways and mTOR and AMPK signaling have been suggested to play a role in the complex changes in key biological networks involved in cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence [...] Read more.
Aging results from the progressive dysregulation of several molecular pathways and mTOR and AMPK signaling have been suggested to play a role in the complex changes in key biological networks involved in cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence progression, one of the meaningful aspects of aging. Unsurprisingly, nutraceutical and pharmacological interventions could help maintain an optimal biological response by providing essential bioactive micronutrients required for the development, maintenance, and the expression of the immune response at all stages of life. In this regard, many studies have provided evidence of potential antiaging properties of resveratrol, as well as rapamycin and metformin. Indeed, in vitro and in vivo models have demonstrated for these molecules a number of positive effects associated with healthy aging. The current review focuses on the mechanisms of action of these three important compounds and their suggested use for the clinical treatment of immunosenescence and aging. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

20 pages, 987 KiB  
Review
Utilization of Aloe Compounds in Combatting Viral Diseases
by Erica Españo, Jiyeon Kim and Jeong-Ki Kim
Pharmaceuticals 2022, 15(5), 599; https://doi.org/10.3390/ph15050599 - 13 May 2022
Cited by 8 | Viewed by 3720
Abstract
Plants contain underutilized resources of compounds that can be employed to combat viral diseases. Aloe vera (L.) Burm. f. (syn. Aloe barbadensis Mill.) has a long history of use in traditional medicine, and A. vera extracts have been reported to possess a huge [...] Read more.
Plants contain underutilized resources of compounds that can be employed to combat viral diseases. Aloe vera (L.) Burm. f. (syn. Aloe barbadensis Mill.) has a long history of use in traditional medicine, and A. vera extracts have been reported to possess a huge breadth of pharmacological activities. Here, we discuss the potential of A. vera compounds as antivirals and immunomodulators for the treatment of viral diseases. In particular, we highlight the use of aloe emodin and acemannan as lead compounds that should be considered for further development in the management and prevention of viral diseases. Given the immunomodulatory capacity of A. vera compounds, especially those found in Aloe gel, we also put forward the idea that these compounds should be considered as adjuvants for viral vaccines. Lastly, we present some of the current limitations to the clinical applications of compounds from Aloe, especially from A. vera. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

20 pages, 5024 KiB  
Review
Antiviral Activities of Andrographolide and Its Derivatives: Mechanism of Action and Delivery System
by Sya’ban Putra Adiguna, Jonathan Ardhianto Panggabean, Akhirta Atikana, Febriana Untari, Fauzia Izzati, Asep Bayu, A’liyatur Rosyidah, Siti Irma Rahmawati and Masteria Yunovilsa Putra
Pharmaceuticals 2021, 14(11), 1102; https://doi.org/10.3390/ph14111102 - 28 Oct 2021
Cited by 19 | Viewed by 8345
Abstract
Andrographispaniculata (Burm.f.) Nees has been used as a traditional medicine in Asian countries, especially China, India, Vietnam, Malaysia, and Indonesia. This herbaceous plant extract contains active compounds with multiple biological activities against various diseases, including the flu, colds, fever, diabetes, hypertension, and [...] Read more.
Andrographispaniculata (Burm.f.) Nees has been used as a traditional medicine in Asian countries, especially China, India, Vietnam, Malaysia, and Indonesia. This herbaceous plant extract contains active compounds with multiple biological activities against various diseases, including the flu, colds, fever, diabetes, hypertension, and cancer. Several isolated compounds from A. paniculata, such as andrographolide and its analogs, have attracted much interest for their potential treatment against several virus infections, including SARS-CoV-2. The mechanisms of action in inhibiting viral infections can be categorized into several types, including regulating the viral entry stage, gene replication, and the formation of mature functional proteins. The efficacy of andrographolide as an antiviral candidate was further investigated since the phytoconstituents of A. paniculata exhibit various physicochemical characteristics, including low solubility and low bioavailability. A discussion on the delivery systems of these active compounds could accelerate their development for commercial applications as antiviral drugs. This study critically reviewed the current antiviral development based on andrographolide and its derivative compounds, especially on their mechanism of action as antiviral drugs and drug delivery systems. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

23 pages, 869 KiB  
Review
Plant-Derived Antimicrobial Peptides as Potential Antiviral Agents in Systemic Viral Infections
by Nour Mammari, Ysaline Krier, Quentin Albert, Marc Devocelle, Mihayl Varbanov and on behalf of the OEMONOM
Pharmaceuticals 2021, 14(8), 774; https://doi.org/10.3390/ph14080774 - 06 Aug 2021
Cited by 16 | Viewed by 5399
Abstract
Numerous studies have led to a better understanding of the mechanisms of action of viruses in systemic infections for the development of prevention strategies and very promising antiviral therapies. Viruses still remain one of the main causes of human diseases, mainly because the [...] Read more.
Numerous studies have led to a better understanding of the mechanisms of action of viruses in systemic infections for the development of prevention strategies and very promising antiviral therapies. Viruses still remain one of the main causes of human diseases, mainly because the development of new vaccines is usually challenging and drug resistance has become an increasing concern in recent decades. Therefore, the development of potential antiviral agents remains crucial and is an unmet clinical need. One abundant source of potential therapeutic molecules are plants: they biosynthesize a myriad of compounds, including peptides which can have antimicrobial activity. Our objective is to summarize the literature on peptides with antiviral properties derived from plants and to identify key features of these peptides and their application in systemic viral infections. This literature review highlights studies including clinical trials which demonstrated that plant cyclotides have the ability to inhibit the growth of viruses causing human diseases, defensin-like peptides possess anti-HIV-1 activity, and lipid transfer proteins and some lectins exhibit a varied antimicrobial profile. To conclude, plant peptides remain interesting to explore in the context of emerging and re-emerging infectious diseases. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Graphical abstract

Other

Jump to: Research, Review

19 pages, 2835 KiB  
Systematic Review
An Evaluation of the Potential of Essential Oils against SARS-CoV-2 from In Silico Studies through the Systematic Review Using a Chemometric Approach
by Luiz Torres Neto, Maria Lúcia Guerra Monteiro, Diego Galvan and Carlos Adam Conte-Junior
Pharmaceuticals 2021, 14(11), 1138; https://doi.org/10.3390/ph14111138 - 10 Nov 2021
Cited by 13 | Viewed by 3898
Abstract
Essential oils (EOs) and their compounds have attracted particular attention for their reported beneficial properties, especially their antiviral potential. However, data regarding their anti-SARS-CoV-2 potential are scarce in the literature. Thus, this study aimed to identify the most promising EO compounds against SARS-CoV-2 [...] Read more.
Essential oils (EOs) and their compounds have attracted particular attention for their reported beneficial properties, especially their antiviral potential. However, data regarding their anti-SARS-CoV-2 potential are scarce in the literature. Thus, this study aimed to identify the most promising EO compounds against SARS-CoV-2 based on their physicochemical, pharmacokinetic, and toxicity properties. A systematic literature search retrieved 1669 articles; 40 met the eligibility criteria, and 35 were eligible for analysis. These studies resulted in 465 EO compounds evaluated against 11 human and/or SARS-CoV-2 target proteins. Ninety-four EO compounds and seven reference drugs were clustered by the highest predicted binding affinity. Furthermore, 41 EO compounds showed suitable drug-likeness and bioactivity score indices (≥0.67). Among these EO compounds, 15 were considered the most promising against SARS-CoV-2 with the ADME/T index ranging from 0.86 to 0.81. Some plant species were identified as EO potential sources with anti-SARS-CoV-2 activity, such as Melissa officinalis Arcang, Zataria multiflora Boiss, Eugenia brasiliensis Cambess, Zingiber zerumbet Triboun & K.Larsen, Cedrus libani A.Rich, and Vetiveria zizanoides Nash. Our work can help fill the gap in the literature and guide further in vitro and in vivo studies, intending to optimize the finding of effective EOs against COVID-19. Full article
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-19
Back to TopTop