• Antiviral
• antiviral properties
• infection
• natural herbal drugs
• plant extract.
• vaccines
• virus replication

• Antiviral Agents/pharmacology
• Antiviral Agents/chemistry
• Antiviral Agents/isolation & purification
• Humans
• Biological Products/pharmacology
• Biological Products/chemistry
• Biological Products/isolation & purification
• Plants, Medicinal/chemistry
• Plant Extracts/pharmacology
• Plant Extracts/chemistry
• Plant Extracts/isolation & purification
• Viruses/drug effects
• Animals
• Virus Diseases/drug therapy

• Alkaline nuclease
• BGLF5
• EBV DNase
• Fluorescence
• PicoGreen

• Humans
• Emodin/pharmacology
• Herpesvirus 4, Human/genetics
• Epstein-Barr Virus Infections
• DNA
• Deoxyribonucleases/chemistry
• Deoxyribonucleases/genetics

• DMR-110-184 China Medical University Hospital, Taiwan
• MOST 110-2320-B-039-009 National Science and Technology Council, Taiwan

• PI4KB
• antiviral
• edible plant
• enterovirus
• picornavirus
• virus

• 22K07107 Japan Society for the Promotion of Science
• 22fk0108627j0001 Japan Agency for Medical Research and Development
• 22fk0108627h1101 Japan Agency for Medical Research and Development

• COVID-19
• influenza
• molecular docking (MD)
• respiratory viruses
• β-sitosterol

• TT110801 National Research Centre
• 12010126 National Research Centre

• Anthraquinones
• Antiviral potential
• Asphodelaceae
• Polygonaceae
• Rubiaceae
• SARS-COVID-19

• Asphodelaceae
• Dianella ensifolia
• flavan
• tyrosinase

• CMU110-Z-08 and CMU109-AWARD-02 China Medical University
• KMU-M109024, M110027, and M111004 Kaohsiung Medical University
• CMRC-CHM-2-1 The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan

Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities.

Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan.

Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven.

Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, p = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, p = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported.

Conclusion: The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted.

Clinical Trial Registration:Clinicaltrials.gov, identifier NCT05130671

Hepatitis C virus infection is the main cause of liver ailments across the globe. Several HCV genotypes have been identified in different parts of the world. Effective drugs for combating HCV infections are available but not affordable, particularly to infected individuals from resource-limited countries. Hence, cost-effective drugs need to be developed against important HCV drug targets. As Citrus fruits naturally contain bioactive compounds with antiviral activities, the current study was designed to identify antiviral inhibitors from Citrus fruit extracts against an important drug target, NS3 protease, of HCV genotype 3a which is found predominantly in South Asian countries.

The full-length NS3 protease alone and the NS3 protease domain in fusion with the cognate NS4A cofactor were expressed in Escherichia coli, and purified by chromatographic techniques. Using the purified protein as a drug target, Citrus extracts were evaluated in a FRET assay, and active ingredients, identified using ESI–MS/MS, were docked to observe the interaction with active site residues of NS3. The best interacting compound was further confirmed through the FRET assay as the inhibitor of NS3 protease.

Fusion of the NS3 protease domain to the NS4A cofactor significantly improved the purification yield, and NS3-NS4A was functionally more active than the full-length NS3 alone. The purified protein (NS3-NS4A) was successfully employed in a validated FRET assay to evaluate 14 Citrus fruit extracts, revealing that the mesocarp extract of Citrus paradisi, and whole fruit extracts of C. sinesis, C. aurantinum, and C. reticulata significantly inhibited the protease activity of HCV NS3 protease (IC₅₀ values of 5.79 ± 1.44 µg/mL, 37.19 ± 5.92 µg/mL, 42.62 ± 6.89 µg/mL, and 57.65 ± 3.81 µg/mL, respectively). Subsequent ESI-MSⁿ analysis identified a flavonoid, hesperidin, abundantly present in all the afore-mentioned Citrus extracts. Importantly, docking studies suggested that hesperidin interacts with active site residues, and acts as a potent inhibitor of NS3 protease, exhibiting an IC₅₀ value of 11.34 ± 3.83 µg/mL.

A FRET assay was developed using NS3-NS4A protease, which was successfully utilized for the evaluation of Citrus fruit extracts. Hesperidin, a compound present in the Citrus extracts, was identified as the main flavonoid, which can serve as a cost-effective potent inhibitor of NS3 protease, and could be developed as a drug for antiviral therapy against HCV genotype 3a.

The online version contains supplementary material available at 10.1186/s12906-022-03578-1.

• antiviral activities
• emodin
• halogenated emodin
• human coronavirus NL63

• Adenosine Monophosphate/analogs & derivatives
• Adenosine Monophosphate/pharmacology
• Adenosine Monophosphate/therapeutic use
• Alanine/analogs & derivatives
• Alanine/pharmacology
• Alanine/therapeutic use
• Animals
• Antiviral Agents/chemical synthesis
• Antiviral Agents/chemistry
• Antiviral Agents/pharmacology
• Antiviral Agents/therapeutic use
• Cell Survival/drug effects
• Chlorocebus aethiops
• Coronavirus Infections/drug therapy
• Coronavirus Infections/virology
• Coronavirus NL63, Human/drug effects
• Coronavirus NL63, Human/isolation & purification
• Emodin/analogs & derivatives
• Emodin/chemical synthesis
• Halogenation
• Humans
• Vero Cells

• P1-0134 Slovenian Research Agency
• P4-0116 Slovenian Research Agency

• AutoDock Vina
• COVID-19
• SARS-CoV-2
• anthraquinone
• flavonoids
• hydroxychloroquine
• peptide mass fingerprinting

• Anthraquinones
• Flavonoids/pharmacology
• Humans
• Hydroxychloroquine
• Moringa oleifera
• Peptides
• RNA, Viral
• SARS-CoV-2
• COVID-19 Drug Treatment

• COVID-19
• TCM
• coronavirus
• dietary supplementation
• herbal medicine
• plant
• secondary metabolites

• COVID-19
• Corona virus
• Drug repurposing
• Medicinal plants
• Pandemic

• Antiviral Agents/therapeutic use
• Drug Repositioning
• Humans
• Phytotherapy
• Plants, Medicinal
• COVID-19 Drug Treatment

• 5α-reductase
• Androgenic alopecia
• Hair
• Physcion

• 5-alpha Reductase Inhibitors/chemistry
• 5-alpha Reductase Inhibitors/pharmacology
• Alopecia/drug therapy
• Animals
• Emodin/analogs & derivatives
• Emodin/chemistry
• Emodin/pharmacology
• Hair Follicle/drug effects
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Plant Extracts/chemistry
• Plant Extracts/pharmacology
• Rats
• Rats, Sprague-Dawley

• antibiotics
• biotechnology
• extreme habitats
• extremophiles
• micromycetes
• resistance

The pandemic disease COVID-19, caused by SARS CoV-2, has created a global crisis. Presently, researchers across the globe are in a quest to identify/develop drugs or vaccines by targeting different non-structural proteins (Nsps) of SARS CoV-2. One such important drug target is Nsp5/main protease (Mpro) which plays a critical role in the viral replication. This cysteine protease/Mpro of SARS CoV-2 has high sequence similarity with the same protease from SARS CoV-1. Previously, it has been shown experimentally that eight polyphenols derived from the root of Isatis indigotica show inhibitory effect on the cleavage/catalytic activity of the SARS CoV-1 Mpro. But whether these polyphenols exhibit any inhibitory effect on SARS CoV-2 Mpro is unclear. To explore this possibility, here, we have adopted various computational approaches. Polyphenols that qualified the pharmacological parameters (indigo, sinigrin, hesperetin and daidzein) and two well-known Mpro inhibitors (N3 and lopinavir) were subjected to molecular docking studies. Two of them (sinigrin and hesperetin) were selected by comparing their binding affinities with N3 and lopinavir. Sinigrin and hesperetin interacted with the two most important catalytic residues of Mpro (His41 and Cys145). Molecular dynamics studies further revealed that these two Mpro-polyphenol complexes are more stable and experience less conformational fluctuations than Mpro-N3/lopinavir complex. The Mpro-hesperetin complex was more compact and less expanded than Mpro-sinigrin complex. These findings were additionally validated by MM-GBSA analysis. As a whole, our study revealed that these two polyphenols may be potent SARS CoV-2 Mpro inhibitors and may possibly be considered for COVID-19 treatment.

• COVID-19
• Isatis indigotica polyphenols
• SARS CoV-2 main protease
• docking
• molecular dynamics simulation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) is a well-characterized therapeutic target which is a key player driving the viral replication and transcription machinery. The recent elucidation of the experimental structure of SARS-CoV-2 RdRp enzyme complexed with triphosphate form of Remdesivir (RTP) has opened an avenue for structure-based identification of potent inhibitors. Given the high mortality rate of the coronavirus disease 2019 (COVID-19) and lack of effective therapeutics against it, an alternative for safe and speedy drug discovery needs to be sought after. One promising strategy could be to explore the possibility for repurposing the Food and Drug Administration (FDA) approved antiviral drugs and antiviral phytocompounds. In the present study, a set of FDA approved antiviral drugs and antiviral phytocompounds were screened for their ability to bind within the RdRp enzyme active pocket. The top 3 hits among the FDA approved drugs were Paritaprevir (D33), Rilpivirine (D19) and Simeprevir (D31) which scored binding energies between −8.08 kcal/mol and −10.46 kcal/mol. Emetine (P5), 7,4-di-O-galloyltricetifavan (P28) and Oleanolic acid (P17) were the top three phytocompounds hits and exhibited binding energies ranging from −7.81 kcal/mol to −8.17 kcal/mol. These drugs and phytocompounds were able to establish hydrogen bonds with the catalytic residues-Asp760 and Asp761 and hydrophobic interactions with neighbouring residues. Further, the physicochemical properties of the molecules were evaluated. These identified potential inhibitors warrant further experimental investigations before their acceptance as drug candidates for the treatment of the disease.

• Antivirals
• COVID-19
• FDA approved drugs
• Nps12
• Phytocompounds
• RdRp
• Remdesivir
• SARS-CoV-2

The highly contagious nature of SARS-CoV-2 (COVID-19) virus has created a havoc effect all over the world in a very short period. The most effective method for precaution of this virus as suggested by WHO is use of PPEs (triple layered face mask, body suits) and social distancing. However, the frontline doctors and medical staff have high risk of exposure to the virus during treatments and removal and discarding of the PPEs. Also the PPEs are of the onetime use and wearing these PPEs in hot and humid seasons is very uncomfortable. A possible solution of this problem is if clothes are anti-bacterial and anti-viral in nature, one single-layered will be sufficient and the spread of virus will also be minimized. Considering this, we have designed a facile and durable anti-wash antimicrobial coating on cloth by aloe vera and hexadecyltrimethoxysilane (HDTMS). In lab scale study, present coating shows good chemical and thermal stability making it reusable multiple times even after repeated washing. The coated cloth reveals the excellent anti-dirt and stain resistance properties leading to complete non-adherence of dirt and stain (e.g. Color, food, ink) on it. Anti-bacterial and anti-fungi properties of the coated cloth were confirmed by doing E. coli (bacteria) and A. Niger (fungus) culture studies, respectively. This coating is imbibed with well-known anti-viral agent aloe vera which inhibits the attachment of the virus on the surface. The water-repellent nature of the coating combined with the use anti-viral agent, aloe vera makes it a potential anti-COVID-19 coating.

• Citrus extract
• Fluorescence resonance energy transfer assay
• Hepatitis C virus genotype 3a
• Hesperidin
• Mass spectrometry
• Non-structural protein 3 protease

• anthraquinone
• cancer
• kinases
• nanoparticles
• telomerase
• topoisomerase

• Rhamnosyltransferase
• Saccharothrix espanaensis
• quinizain

• HBV polymerase
• aloe
• anthraquinones
• anti-HBV
• hepatitis B virus

• Aloe/chemistry
• Anthraquinones/pharmacology
• Anthraquinones/therapeutic use
• Antiviral Agents/pharmacology
• Antiviral Agents/therapeutic use
• Cell Line
• Emodin/analogs & derivatives
• Emodin/pharmacology
• Emodin/therapeutic use
• Hep G2 Cells
• Hepatitis B/drug therapy
• Hepatitis B virus/drug effects
• Humans
• Phytotherapy/methods
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use

• RG-1435-053 The Deanship of Scientific Research, King Saud University, Riyadh

• HSV-1
• R. tanguticum nanoparticles
• antiviral
• mouse model
• viral protein

• 3AB, 3-aminobenzamide
• ADR, adriamycin
• ANOVA, one-way analysis of variance
• Apoptosis
• CHR, chrysophanol
• CMC-Na, sodium carboxymethyl
• CO, cardiac output
• Cardiotoxicity
• Chrysophanol
• Cyt c, Cytochrome c
• DOX, doxorubicin
• Doxorubicin
• EF, ejection fraction
• FBS, fetal bovine serum
• FS, fractional shortening
• HE, hematoxylin-eosin
• HR, heart rate
• IVSd, end-diastolic interventricular septum
• IVSs, end-systolic interventricular septum
• LV, end-systolic volume
• LVEDV, LV end-diastolic volume
• LVIDd, LV end-diastolic internal diameter
• LVIDs, LV end-systolic internal diameter
• LVPWd, LV end-diastolic posterior wall thickness
• LVPWs, LV end-systolic posterior wall thickness
• Mitochondria
• NS, normal saline
• PAR, polymers of ADP-ribose
• PARP1, poly(ADP-ribose) polymerase 1
• PARylated, poly(ADP-ribosyl)ated
• PARylation
• PARylation, poly(ADP-ribosyl)ation
• PBS, phosphate-buffered saline
• RCR, respiratory control ratio
• ROS, reactive oxygen species
• Rh123, rhodamine 123
• SD, Sprague–Dawley
• TUNEL, TdT-mediated dUTP nick end labeling
• VDAC1, voltage dependent anion channel 1

• anthraquinone
• chrysophanol
• pharmacokinetics
• pharmacology
• toxicity

• Anthraquinones/chemistry
• Anthraquinones/pharmacology
• Anthraquinones/therapeutic use
• Anti-Bacterial Agents/chemistry
• Anti-Bacterial Agents/pharmacology
• Anti-Inflammatory Agents/chemistry
• Anti-Inflammatory Agents/pharmacology
• Antineoplastic Agents, Phytogenic/chemistry
• Antineoplastic Agents, Phytogenic/pharmacology
• Biological Products/chemistry
• Biological Products/pharmacology
• Biological Products/therapeutic use
• Humans
• Molecular Conformation
• Neuroprotective Agents/chemistry
• Neuroprotective Agents/pharmacology

• Sanhuang Xiexin decoction
• acute ischemic stroke
• endovascular intervention
• inflammatory factors

The viral infection and resistance to the existing antiviral drugs are alarming, which is a serious public health concern. Medicinal plants are valuable resources for treatment of viral infections and can be used for the management of infections like herpes simplex virus (HSV), human immunodeficiency virus (HIV), influenza, etc. The antiviral screening of plant extracts should be highly selective, specific, and sensitive for bioactivity guided isolation of the active compounds from the plant extracts. The antiviral screening system should be validated for accuracy, reproducibility, simplicity, and cost effectiveness. This chapter highlights on various aspects for screening and evaluation of antiviral natural components including factors affecting antiviral in vivo studies, host cells, organisms, and culture media followed by different virus-specific assays for antiviral screening of natural products.

Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin^TM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

• HSV-1
• HSV-2
• antiviral
• natural product
• photodynamic inactivation
• plaque assay

• Animals
• Antiviral Agents/pharmacology
• Antiviral Agents/therapeutic use
• Chlorocebus aethiops
• Fallopia japonica/chemistry
• HEK293 Cells
• HeLa Cells
• Herpes Simplex/drug therapy
• Herpes Simplex/virology
• Herpesvirus 1, Human/drug effects
• Herpesvirus 2, Human/drug effects
• Humans
• Photochemotherapy
• Photosensitizing Agents/pharmacology
• Photosensitizing Agents/therapeutic use
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Plant Roots/chemistry
• Vero Cells

• 507294-16 Natural Sciences and Engineering Research Council of Canada

Cancer is one of the most frequently occurring diseases and is the second leading cause of death worldwide. In this study, anthraquinone derivatives (Compounds 1–5) were evaluated for their anti-cancer potential against various skin and breast cancer cell lines to assess whether these anthraquinone derivatives may serve as a lead for the augmentation of anti-cancer drug.

Anthraquinone derivatives, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-(6′-O-acetyl)-α-rhamnosyl(1 → 2)-β-glucoside (Comp 1), 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone (Comp 2), and alizarin (Comp 3) were isolated from the dichloromethane fraction of the roots of Rubia philippinensis., whereas ethyl acetate fraction yielded xanthopurpurin (Comp 4) and lucidin-ω-methyl ether (Comp 5). Structures of all the isolated compounds were determined by spectral data analysis. All isolated compounds (Comp 1–5) were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against four different cancer cell lines, i.e. human melanoma (SK-MEL-5), murine melanoma (B16F10), and human breast adenocarcinoma (MCF7 and MDA-MB-231).

Significant activity of the compounds 4 and 5 was observed against the breast cancer cell line MDA-MB-231 with IC₅₀ values of 14.65 ± 1.45 and 13.03 ± 0.33 μM, respectively. Encouragingly, IC₅₀ values of 67.89 ± 1.02 and 79.01 ± 0.03 μM against normal kidney epithelial cells (MDCK) were also obtained for compounds 4 and 5, respectively, which indicated very low toxicity and favorable selectivity indices for compounds 4 and 5 in the range of 1.85 to 3.95 and 2.11 to 6.06 against skin cancer cell lines (SK-MEL-5, and B16F10), and breast cancer cell lines (MCF7 and MDA-MB-231), respectively.

Our results suggested that the compounds 4 (xanthopurpurin) and 5 (lucidin-ω-methyl ether) showed high selective toxicity towards breast cancer cells at lower concentrations without showing toxicity towards normal cells, thus could be of potential as new lead molecules in cancer treatment.

The online version of this article (10.1186/s12906-018-2253-2) contains supplementary material, which is available to authorized users.

• Anthraquinone
• Breast cancer
• Cytotoxicity
• Rubia philippinensis
• Skin cancer

• Aspergillaceae
• Aspergillus candidus
• antibacterial activity
• bis-indolyl benzenoids
• cytotoxicity
• hydroxypyrrolidine
• sponge-associated fungus

• Animals
• Anisomycin/analogs & derivatives
• Anisomycin/chemistry
• Anisomycin/isolation & purification
• Anisomycin/pharmacology
• Anti-Bacterial Agents/chemistry
• Anti-Bacterial Agents/isolation & purification
• Anti-Bacterial Agents/pharmacology
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/isolation & purification
• Antineoplastic Agents/pharmacology
• Aspergillus/chemistry
• Bacteria/drug effects
• Cell Line, Tumor
• Drug Resistance, Bacterial/drug effects
• Drug Synergism
• Humans
• Inhibitory Concentration 50
• Microbial Sensitivity Tests
• Porifera/microbiology
• Pyrrolidines/chemistry
• Pyrrolidines/isolation & purification
• Pyrrolidines/pharmacology
• Terphenyl Compounds/chemistry
• Terphenyl Compounds/isolation & purification

• Anthraquinone
• Anti-inflammatory
• Anticancer
• Antidiabetic
• Antimicrobial
• Antioxidative
• Flavonoid
• Rheum australe
• Stilbenoid

• Department of Science and Technology, Government of India, New Delhi

• Antiviral activity
• Dual inhibitor
• HIV-1
• Plant extracts
• Reverse transcriptase
• Sennoside A

• Anthraquinones/pharmacology
• Anti-HIV Agents/pharmacology
• HIV Infections/drug therapy
• HIV Infections/virology
• HIV Integrase/metabolism
• HIV Reverse Transcriptase/metabolism
• HIV-1/drug effects
• Medicine, Chinese Traditional
• Plant Extracts/pharmacology
• Reverse Transcriptase Inhibitors/pharmacology
• Rheum/chemistry
• Ribonuclease H/metabolism
• Senna Extract/pharmacology
• Sennosides
• Species Specificity
• Virus Replication/drug effects

Many plant essential oils, extracts, and individual chemical components have been demonstrated to possess antiviral efficacy against enveloped and/or non-enveloped viruses. In general, plant antimicrobials exhibit greater antiviral efficacy against enveloped viruses than non-enveloped viruses (though not in all cases). There appear to be multiple mechanisms of antiviral action for plant antimicrobials; nevertheless, the majority of antimicrobials appear to act either directly on the virus itself (e.g., on the envelope or capsid) or during the early stages of virus replication following internalization of the virus into its host cell.

Herpes simplex virus type 1 (HSV-1) is associated with orofacial infections and is transmitted by direct contact with infected secretions. Several efforts have been expended in the search for drugs to the treatment for herpes. Schinus terebinthifolius is used in several illnesses and among them, for the topical treatment of skin wounds, especially wounds of mucous membranes, whether infected or not.

To evaluate the cytotoxicity and anti-HSV-1 activity of the crude hydroethanolic extract (CHE) from the stem bark of S. terebinthifolius, as well as its fractions and isolated compounds.

The CHE was subjected to bioguided fractionation. The anti-HSV-1 activity and the cytotoxicity of the CHE, its fractions, and isolated compounds were evaluated in vitro by SRB method. A preliminar investigation of the action of CHE in the virus–host interaction was conducted by the same assay.

CHE presented flavan-3-ols and showed anti-HSV-1 activity, better than its fractions and isolated compounds. The class of substances found in CHE can bind to proteins to form unstable complexes and enveloped viruses, as HSV-1 may be vulnerable to this action. Our results suggest that the CHE interfered with virion envelope structures, masking viral receptors that are necessary for adsorption or entry into host cells.

The plant investigated exhibited potential for future development treatment against HSV-1, but further tests are necessary, especially to elucidate the mechanism of action of CHE, as well as preclinical and clinical studies to confirm its safety and efficacy.

Crude hydroethanolic extract (CHE) presents promising activity against herpes simplex virus type 1 (HSV 1), with selectivity index (SI) = 22.50

Abbreviations used: HSV: Herpes simplex virus, CHE: Crude hydroethanolic extract, WF: Water fraction, AF: Ethyl-acetate fraction, MPLC: Medium-performance liquid chromatography, TLC: Thin-layer chromatography, NMR: Nuclear magnetic resonance, ESI-MS: Electrospray ionization mass spectrometry, SRB: Sulforhodamine B, CPE: Cytopathic effect, CC50: 50% cytotoxic concentration, EC50: 50% effective concentration, PBS: Phosphate-buffered saline.

• Antiviral activity
• Aroeira
• Schinus terebinthifolius Raddi
• cytotoxicity
• herpes simplex virus
• herpes simplex virus type 1

• anthraquinone
• antibiotic
• antitumor
• biological activity
• cytotoxicity
• fungi
• marine
• pigment

• Animals
• Anthraquinones/metabolism
• Biological Products/metabolism
• Color
• Fungi/metabolism
• Humans

Natural products are the basis of treatment since the dawn of human civilization, and modern medicine has gradually developed, over the years, by scientific and observational efforts from traditional medicine. Today most of the synthetic drugs showed adverse and unacceptable side effects, however, impressive bioactivities with reduced toxicities were reported for many botanicals against several chronic or difficult-to-treat diseases. A whole range of viral diseases including human immunodeficiency virus/acquired immunodeficiency syndrome, severe acute respiratory syndrome, Rabies, Dengue, and Herpes need effective drugs. Considerable research has been carried out on the pharmacognosy, chemistry, pharmacology, and therapeutics of traditional medicines of diverse cultures, and many pharmaceutical companies have renewed their strategies for antiviral drug development where no effective drugs or vaccine exist. Thus, phytochemicals with antiviral potentials need to be studied in depth with standardization, chemical isolation, effectivity, molecular mechanism, along with in vivo toxicity and efficacy to reduce cost and time. This review will portray the scientific approaches and methodologies used for the development of antiviral leads from traditional medicines against selected genetically and functionally diverse viral infections.

•

The anthraquinone atanyl blue PRL inhibits human cytomegalovirus replication.

Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC₅₀ of 4.9 μM but was cytotoxic at concentrations only twofold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238–265 μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC₅₀ of 6.3 μM, significantly below its 50% cytotoxic concentration of 216 μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to 1 h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24 h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC₅₀ of 4.5 and 9.3 μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development.

• Alkaline nuclease
• Anthraquinone
• Antivirals
• Atanyl blue PRL
• Cytomegalovirus

• Anthraquinones/pharmacokinetics
• Caco-2 Cells
• Emodin/pharmacokinetics
• Enzyme Inhibitors/pharmacokinetics
• Humans
• Intestinal Mucosa/metabolism
• Intestines/cytology
• Mutagens/pharmacokinetics

Rheum palmatum, Chinese traditional herb, exhibits a great variety of anti-cancer and anti-viruses properties. This study rates antiviral activity of R. palmatum extracts and its components against Japanese encephalitis virus (JEV) in vitro. Methanol extract of R. palmatum contained higher levels of aloe emodin, chrysophanol, rhein, emodin and physcion than water extract. Methanol extract (IC₅₀ = 15.04 μg/ml) exhibited more potent inhibitory effects on JEV plaque reduction than water extract (IC₅₀ = 51.41 μg/ml). Meanwhile, IC₅₀ values determined by plaque reduction assay were 15.82 μg/ml for chrysophanol and 17.39 μg/ml for aloe-emodin, respectively. Virucidal activity of agents correlated with anti-JEV activity, while virucidal IC₅₀ values were 7.58 μg/ml for methanol extract, 17.36 μg/ml for water extract, 0.75 μg/ml for chrysophanol and 0.46 μg/ml for aloe-emodin, respectively. In addition, 10 μg/ml of extract, chrysophanol or aloe emodin caused 90 % inhibition of JEV yields in cells and significantly activated gamma activated sequence-driven promoters. Hence, methanol extract of R. palmatum and chrysophanol with high therapeutic index might be useful for development of antiviral agents against JEV.

• Fuzi Xiexin Tang
• Sanhuang Xiexin Tang
• UPLC-MS
• alkaloids
• anthraquinones
• categorized formulas
• flavones