scholarly journals Artemisia annua L. extracts prevent in vitro replication of SARS-CoV-2

2021 ◽  
Author(s):  
Manoj S Nair ◽  
Yaoxing Huang ◽  
David A Fidock ◽  
Stephen J Polyak ◽  
Jessica Wagoner ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antimalarial Drug ◽  
Artemisia Annua ◽  
Cost Effective ◽  
Hot Water ◽  
Total Flavonoids ◽  
Leaf Extracts ◽  
Artemisinin Derivatives

SARS-CoV-2 (Covid-19) globally has infected and killed millions of people. Besides remdesivir, there are no approved small molecule-based therapeutics. Here we show that extracts of the medicinal plant, Artemisia annua L., which produces the antimalarial drug artemisinin, prevents SARS-CoV-2 replication in vitro. We measured antiviral activity of dried leaf extracts of seven cultivars of A. annua sourced from four continents. Hot-water leaf extracts based on artemisinin, total flavonoids, or dry leaf mass showed antiviral activity with IC50 values of 0.1-8.7 μM, 0.01-0.14 μg, and 23.4-57.4 μg, respectively. One sample was >12 years old, but still active. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts and antiviral efficacy was inversely correlated to artemisinin and total flavonoid contents. Artemisinin alone showed an estimated IC50 of about 70 μM, and antimalarial artemisinin derivatives artesunate, artemether, and dihydroartemisinin were ineffective or cytotoxic at elevated micromolar concentrations. In contrast, the antimalarial drug amodiaquine had an IC50 = 5.8 μM. The extracts had minimal effects on infection of Vero E6 or Calu-3 cells by a reporter virus pseudotyped by the SARS-CoV-2 spike protein. There was no cytotoxicity within an order of magnitude of the antiviral IC90 values. Results suggest the active component in the extracts is likely something besides artemisinin or is a combination of components acting synergistically to block post-entry viral infection. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.

scholarly journals Artemisia annua hot-water extracts show potent activity in vitro against Covid-19 variants including delta

2021 ◽  
Author(s):  
M.S. Nair ◽  
Y. Huang ◽  
D.A. Fidock ◽  
M.J. Towler ◽  
P.J. Weathers
Keyword(s):  
Artemisia Annua ◽  
Cost Effective ◽  
Dry Weight ◽  
Hot Water ◽  
Artemisinin Derivatives ◽  
Water Extracts ◽  
Global Pandemic ◽  
Oral Consumption ◽  
Tea Infusions

AbstractEthnopharmacological relevanceFor millennia in Southeast Asia, Artemisia annua L. was used to treat “fever”. This medicinal plant is effective against numerous infectious microbial and viral diseases and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria.Aim of the StudyThe SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants.Materials and MethodsUsing Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-water A. annua extracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five fully infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1).ResultsIn addition to being effective against the original wild type WA1, A. annua cultivars A3, BUR, MED and SAM were also potent against all five variants. IC50 and IC90 values based on measured artemisinin content ranged from 0.3-8.4 μM and 1.4-25.0 μM, respectively. The IC50 and IC90 values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0-67.7 μg DW and 59.5-160.6 μg DW, respectively. Cell toxicity was insignificant at a leaf dry weight of ≤50 μg in the extract of any cultivar.ConclusionsResults suggest that oral consumption of A. annua hot-water extracts (tea infusions), could provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.

scholarly journals Cordia americana: Evaluation of in vitro anti-herpes simplex virus activity and in vivo toxicity of leaf extracts

2021 ◽  
pp. 362-368
Author(s):  
Gislaine Franco de Moura- Costa ◽  
Gean Pier Panizzon ◽  
Thalita Zago Oliveira ◽  
Marco Antonio Costa ◽  
João Carlos Palazzo de Mello ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Biological Activities ◽  
Leaf Extracts ◽  
In Vivo Toxicity ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections

scholarly journals Selection of safe artemisinin derivatives using a machine learning-based cardiotoxicity platform and in vitro and in vivo validation

2021 ◽  
Author(s):  
Onat Kadioglu ◽  
Sabine M. Klauck ◽  
Edmond Fleischer ◽  
Letian Shan ◽  
Thomas Efferth
Keyword(s):  
Machine Learning ◽  
In Silico ◽  
Artemisia Annua ◽  
Reproductive Toxicity ◽  
Toxicity Prediction ◽  
Artemisinin Derivatives ◽  
Drug Candidates

AbstractThe majority of drug candidates fails the approval phase due to unwanted toxicities and side effects. Establishment of an effective toxicity prediction platform is of utmost importance, to increase the efficiency of the drug discovery process. For this purpose, we developed a toxicity prediction platform with machine-learning strategies. Cardiotoxicity prediction was performed by establishing a model with five parameters (arrhythmia, cardiac failure, heart block, hypertension, myocardial infarction) and additional toxicity predictions such as hepatotoxicity, reproductive toxicity, mutagenicity, and tumorigenicity are performed by using Data Warrior and Pro-Tox-II software. As a case study, we selected artemisinin derivatives to evaluate the platform and to provide a list of safe artemisinin derivatives. Artemisinin from Artemisia annua was described first as an anti-malarial compound and later its anticancer properties were discovered. Here, random forest feature selection algorithm was used for the establishment of cardiotoxicity models. High AUC scores above 0.830 were achieved for all five cardiotoxicity indications. Using a chemical library of 374 artemisinin derivatives as a case study, 7 compounds (deoxydihydro-artemisinin, 3-hydroxy-deoxy-dihydroartemisinin, 3-desoxy-dihydroartemisinin, dihydroartemisinin-furano acetate-d3, deoxyartemisinin, artemisinin G, artemisinin B) passed the toxicity filtering process for hepatotoxicity, mutagenicity, tumorigenicity, and reproductive toxicity in addition to cardiotoxicity. Experimental validation with the cardiomyocyte cell line AC16 supported the findings from the in silico cardiotoxicity model predictions. Transcriptomic profiling of AC16 cells upon artemisinin B treatment revealed a similar gene expression profile as that of the control compound, dexrazoxane. In vivo experiments with a Zebrafish model further substantiated the in silico and in vitro data, as only slight cardiotoxicity in picomolar range was observed. In conclusion, our machine-learning approach combined with in vitro and in vivo experimentation represents a suitable method to predict cardiotoxicity of drug candidates.

Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids

2018 ◽  
Vol 18 (5) ◽  
pp. 321-368 ◽  
Author(s):  
Juan A. Bisceglia ◽  
Maria C. Mollo ◽  
Nadia Gruber ◽  
Liliana R. Orelli
Keyword(s):  
Drug Targets ◽  
Redox Homeostasis ◽  
Cost Effective ◽  
Structural Features ◽  
Mammalian Host ◽  
Neglected Diseases ◽  
Nitrogen Compounds ◽  
Chemical Structures

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

scholarly journals Facile sonochemical-assisted synthesis of orthorhombic phase black phosphorus/rGO hybrids for effective photothermal therapy

Nanophotonics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 3023-3034
Author(s):  
Weiyuan Liang ◽  
Dou Wang ◽  
Xiaohui Ren ◽  
Chenchen Ge ◽  
Hanyue Wang ◽  
...  
Keyword(s):  
Electrode Materials ◽  
Orthorhombic Phase ◽  
Cost Effective ◽  
Black Phosphorus ◽  
Antitumor Effects ◽  
Covalent Bonds ◽  
Preparation Conditions ◽  
Reduced Graphene

AbstractTwo-dimensional black phosphorus (BP) has been demonstrated to be promising in photoelectronic devices, electrode materials, and biomedicine owing to its outstanding properties. However, the application of BP has been hindered by harsh preparation conditions, high costs, and easy degradation in ambient condition. Herein, we report a facile and cost-effective strategy for synthesis of orthorhombic phase BP and a kind of BP-reduced graphene oxide (BP/rGO) hybrids in which BP remains stable for more than 4 weeks ascribed to the formation of phosphorus-carbon covalent bonds between BP and rGO as well as the protection effect of the unique wrinkle morphology of rGO nanosheets. Surface modification BP/rGO hybrids (PEGylated BP/rGO) exhibit excellent photothermal performance with photothermal conversion efficiency as high as 57.79% at 808 nm. The BP/rGO hybrids exhibit enhanced antitumor effects both in vitro and in vivo, showing promising perspectives in biomedicine.

scholarly journals Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zeping Qiu ◽  
Jingwen Zhao ◽  
Fanyi Huang ◽  
Luhan Bao ◽  
Yanjia Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Fibrosis ◽  
Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Cost Effective ◽  
Intramyocardial Injection ◽  
Undesirable Consequence ◽  
Adverse Remodeling

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.

Antiviral activity of Mulberroside C against enterovirus A71 in vitro and in vivo

2021 ◽  
pp. 174204
Author(s):  
Yiming Cao ◽  
En Lei ◽  
Lei Li ◽  
Jin Ren ◽  
Xiaoyang He ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Enterovirus A71

scholarly journals Filociclovir Is an Active Antiviral Agent against Ocular Adenovirus Isolates In Vitro and in the Ad5/NZW Rabbit Ocular Model

2021 ◽  
Vol 14 (4) ◽  
pp. 294
Author(s):  
Eric G. Romanowski ◽  
Islam T. M. Hussein ◽  
Steven C. Cardinale ◽  
Michelle M. Butler ◽  
Lucas R. Morin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Topical Treatment ◽  
Antiviral Agent ◽  
Human Adenovirus ◽  
Treatment Groups ◽  
Ocular Infections ◽  
The Mean ◽  
Eye Infection

Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC50) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC50 for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo.

scholarly journals Possible Future Monoclonal Antibody (mAb)-Based Therapy against Arbovirus Infections

2013 ◽  
Vol 2013 ◽  
pp. 1-21 ◽  
Author(s):  
Giuseppe Sautto ◽  
Nicasio Mancini ◽  
Giacomo Gorini ◽  
Massimo Clementi ◽  
Roberto Burioni
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Side Effects ◽  
Antiviral Activity ◽  
The Other ◽  
Viral Escape ◽  
Passive Immunotherapy ◽  
Medical Need

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminaryin vitroandin vivomodels of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.

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