scholarly journals The Petasites hybridus CO2-extract (Ze 339) blocks SARS-CoV-2 replication in vitro

2021 ◽  
Author(s):  
Lorena Urda ◽  
Matthias Heinrich Kreuter ◽  
Jürgen Drewe ◽  
Georg Boonen ◽  
Veronika Butterweck ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Drug ◽  
Plaque Reduction Assay ◽  
Virus Variant ◽  
Antiviral Effects ◽  
Antiviral Activities ◽  
Pre Treatment ◽  
Novel Coronavirus ◽  
Original Virus

AbstractThe coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2-extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE- and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2 infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, repectively. The IC50 values obtained for isopetasin ranged between 0.37-0.88 μM for both virus variants, that of remdesivir between 1.53-2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-Cov-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

scholarly journals The Petasites hybridus CO2 Extract (Ze 339) Blocks SARS-CoV-2 Replication In Vitro

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 106
Author(s):  
Lorena Urda ◽  
Matthias Heinrich Kreuter ◽  
Jürgen Drewe ◽  
Georg Boonen ◽  
Veronika Butterweck ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Drug ◽  
Plaque Reduction Assay ◽  
Virus Variant ◽  
Ic50 Values ◽  
Antiviral Activities ◽  
Pre Treatment ◽  
Novel Coronavirus ◽  
Original Virus

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2 extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, respectively. The IC50 values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

scholarly journals A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19

2020 ◽  
Author(s):  
Fang Zheng ◽  
Yanwen Zhou ◽  
Zhiguo Zhou ◽  
Fei Ye ◽  
Baoying Huang ◽  
...  
Keyword(s):  
Viral Replication ◽  
Antiviral Drug ◽  
Protein Drug ◽  
Clearance Rates ◽  
Open Label ◽  
Antiviral Effects ◽  
Parallel Group ◽  
Antiviral Activities ◽  
Novel Protein

AbstractBackgroundNovaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19.MethodsIn laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patientsResultsNovaferon inhibited the viral replication in infected cells (EC50=1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC50=0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group.ConclusionsNovaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon.

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

scholarly journals Recombinant Green Fluorescent Protein-Expressing Human Cytomegalovirus as a Tool for Screening Antiviral Agents

2000 ◽  
Vol 44 (6) ◽  
pp. 1588-1597 ◽  
Author(s):  
Manfred Marschall ◽  
Martina Freitag ◽  
Sigrid Weiler ◽  
Gabriele Sorg ◽  
Thomas Stamminger
Keyword(s):  
Green Fluorescent Protein ◽  
Human Cytomegalovirus ◽  
Fluorescent Protein ◽  
Antiviral Agents ◽  
Inhibitory Effects ◽  
Plaque Reduction Assay ◽  
Human Fibroblast Cultures ◽  
Antiviral Activities ◽  
Green Fluorescent

ABSTRACT A recombinant human cytomegalovirus (AD169-GFP) expressing green fluorescent protein was generated by homologous recombination. Infection of human fibroblast cultures with AD169-GFP virus produced stable and readily detectable amounts of GFP signals which were quantitated by automated fluorometry. Hereby, high levels of sensitivity and reproducibility could be achieved, compared to those with the conventional plaque reduction assay. Antiviral activities were determined for four reference compounds as well as a set of putative novel cytomegalovirus inhibitors. The results obtained were exactly in line with the known characteristics of reference compounds and furthermore revealed distinct antiviral activities of novel in vitro inhibitors. The fluorometric data could be confirmed by GFP-based flow cytometry and fluorescence microscopy. In addition, laboratory virus variants derived from the recombinant AD169-GFP virus provided further possibilities for study of the characteristics of drug resistance. The GFP-based antiviral assay appeared to be very reliable for measuring virus-inhibitory effects in concentration- and time-dependent fashions and might also be adaptable for high-throughput screenings of cytomegalovirus-specific antiviral agents.

scholarly journals The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 361
Author(s):  
Natalya Bukreyeva ◽  
Rachel A. Sattler ◽  
Emily K. Mantlo ◽  
Timothy Wanninger ◽  
John T. Manning ◽  
...  
Keyword(s):  
Disease Burden ◽  
Vero Cells ◽  
The United States ◽  
The Novel ◽  
Infectious Titer ◽  
Adenosine Analogue ◽  
Pre Treatment ◽  
Novel Coronavirus ◽  
Dose Dependent

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing COVID-19 pandemic, which has resulted in over 2.5 million confirmed cases and 170,000 deaths worldwide as of late April 2020. The pandemic currently presents major public health and economic burdens worldwide. No vaccines or therapeutics have been approved for use to treat COVID-19 cases in the United States despite the growing disease burden, thus creating an urgent need for effective treatments. The adenosine analogue remdesivir (REM) has recently been investigated as a potential treatment option, and has shown some activity in limiting SARS-CoV-2 replication. We previously reported that the IMPDH inhibitor merimepodib (MMPD) provides a dose-dependent suppression of SARS-CoV-2 replication in vitro. Here, we report that a 4-hour pre-treatment of Vero cells with 2.5µM MMPD reduces the infectious titer of SARS-CoV-2 more effectively than REM at the same concentration. Additionally, pre-treatment of Vero cells with both REM and MMPD in combination reduces the infectious titer of SARS-CoV-2 to values below the detectable limit of our TCID50 assay. This result was achieved with concentrations as small as 1.25 µM MMPD and 2.5 µM REM. At concentrations of each agent as low as 0.31 µM, significant reduction of viral production occurred. This study provides evidence that REM and MMPD administered in combination might be an effective treatment for COVID-19 cases.

scholarly journals Amphotericin B from antifungal to antiviral therapy: promising modern therapeutic branch

2020 ◽  
Vol 6 (2) ◽  
pp. 57-65
Author(s):  
Falah Hasan Obayes AL-Khikani
Keyword(s):  
Amphotericin B ◽  
Viral Infections ◽  
Wide Spectrum ◽  
Therapeutic Option ◽  
Antiviral Drug ◽  
Membrane Integrity ◽  
Viral Envelope ◽  
Antimicrobial Efficiency

Introduction: Amphotericin B (AmB) which belongs to the polyene group has a wide spectrum in vitro and in vivo antimicrobial activity against fungi and parasites, but resistance to AmB is rare despite extensive use. Material and methods: Atotal of 2530 articles were investigated in PubMed (n = 1525), Medline (n = 705), and Google Scholar (n = 300). From 2530 articles, only 61 studies were included in this review. All the short and full articles were searched that were scheduled to be published until April 2020. Results: After its discovery, AmB has been one of the most common first-line choices in treating systemic fungal infection for over seven decades from its discovery. Recently, some studies have focused on the potential antimicrobial action of AmB against some enveloped and non-enveloped viruses, such as human immunodeficiency virus, Japanese encephalitis virus, herpes simplex virus, and Rubella virus. Discussion: Among the invading pathogens, viruses constitute the most common ones,Due to the continuous spreading of viral infections with the rise in death numbers, new therapeutics development is urgent, as in general, some lethal viruses have no specific antiviral drugs or vaccines. So, this review may serve as an impetus for researchers working in the field of medical microbiology, vaccination, and antiviral drug design by discussing the most recent information about the antiviral action of AmB, as well as trying to provide a deeper understanding of major properties, mechanisms of action, immune system responses, and antimicrobial efficiency of AmB. Conclusion: Since AmB is expected to alter the structure of the viral envelope, membrane integrity of cells, and internal cellular organelles, besides its other unique properties, such as host immunomodulatory effects, this review suggested that AmB as an effective anti-fungi drug may hold the promise of formulating a novel therapeutic option to treat many dangerous viruses, including those for treating which there are no active drugs or vaccines.

Molecular adduct of amantadine ferulate presents a pathway for slowing in vitro/vivo releases and raising synergistic antiviral effects via dual optimization salification strategy

CrystEngComm ◽  
2021 ◽  
Author(s):  
Yuan-Yuan Niu ◽  
Ling-Yang Wang ◽  
Yue-Ming Yu ◽  
Yan-Tuan Li ◽  
Zhi-Yong Wu ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Antiviral Effects ◽  
Molecular Adduct ◽  
Molecular Salt

The first synthesized antiviral drug-nutriment molecular salt demonstrating simultaneous slowed-release and synergistically enhanced antiviral effects is studied theoretically and experimentally.

scholarly journals Use of Cotton Rats to Evaluate the Efficacy of Antivirals in Treatment of Measles Virus Infections

2000 ◽  
Vol 44 (5) ◽  
pp. 1146-1152 ◽  
Author(s):  
Philip R. Wyde ◽  
Donna K. Moore-Poveda ◽  
Erik De Clercq ◽  
Johan Neyts ◽  
Akira Matsuda ◽  
...  
Keyword(s):  
Measles Virus ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Virus Infections ◽  
Virus Inoculation ◽  
Similar Dose ◽  
Cotton Rats ◽  
Antiviral Activities ◽  
Syncytial Virus

ABSTRACT No practical animal models for the testing of chemotherapeutic or biologic agents identified in cell culture assays as being active against measles virus (MV) are currently available. Cotton rats may serve this purpose. To evaluate this possibility, 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR) and poly(acrylamidomethyl propanesulfonate) (PAMPS), two compounds that have been reported to inhibit MV in vitro, and ribavirin, an established antiviral drug with MV-inhibitory activity, were evaluated for their antiviral activities against MV and respiratory syncytial virus (RSV) in tissue culture and in hispid cotton rats. A single administration of PAMPS markedly inhibited pulmonary RSV or MV replication (>3 log10 reduction in pulmonary titer compared to that for controls), but only if this compound was administered intranasally at about the time of virus inoculation. Both EICAR and ribavirin exhibited therapeutic activity against RSV and MV in cotton rats when they were administered parenterally. However, both of these compounds were less effective against MV. On the basis of the pulmonary virus titers on day 4 after virus inoculation, the minimal efficacious dose of EICAR against MV (120 mg/kg of body weight/day when delivered intraperitoneally twice daily) appeared to be three times lower against this virus than that of ribavirin delivered at a similar dose (i.e., 360 mg/kg/day). These findings correlated with those obtained in vitro. The data obtained suggest that cotton rats may indeed be useful for the initial evaluation of the activities of antiviral agents against MV.

scholarly journals Modulating the Heat Sensitivity of Prostate Cancer Cell Lines In Vitro: A New Impact for Focal Therapies

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 585
Author(s):  
Oliver Hahn ◽  
Franziska M. Heining ◽  
Jörn Janzen ◽  
Johanna C. R. Becker ◽  
Marina Bertlich ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Therapeutic Option ◽  
Neuroendocrine Differentiation ◽  
High Intensity Focused Ultrasound ◽  
Heat Sensitivity ◽  
Heat Response ◽  
Pre Treatment ◽  
The Impact

Focal therapies such as high-intensity focused ultrasound (HiFU) are an emerging therapeutic option for prostate cancer (PCA). Thermal or mechanical effects mediate most therapies. Moreover, locally administered drugs such as bicalutamide or docetaxel are new focal therapeutic options. We assessed the impact of such focal medical treatments on cell viability and heat sensitivity by pre-treating PCA cell lines and then gradually exposing them to heat. The individual heat response of the cell lines tested differed largely. Vertebral-Cancer of the Prostate (VCaP) cells showed an increase in metabolic activity at 40–50 °C. Androgen receptor (AR)-negative PC3 cells showed an increase at 51.3 °C and were overall more resistant to higher temperatures. Pre-treatment of VCaP cells with testosterone (VCaPrev) leads to a more PC3-like kinetic of the heat response. Pre-treatment with finasteride and bicalutamide did not cause changes in heat sensitivity in any cell line. Mitoxantrone treatment, however, shifted heat-induced proliferation loss to lower temperature in VCaP cells. Further analysis via RNAseq identified a possible correlation of heat resistance with H3K27me3-dependent gene regulation, which could be related to an increase in the histone methyltransferase EZH2 and a possible neuroendocrine differentiation. Pre-treatment with mitoxantrone might be a perspective for HiFU treatment. Further studies are needed to evaluate possible combinations with Hsp90 or EZH2 inhibitors.

scholarly journals Anti-Respiratory Syncytial Virus Activity of Plantago asiatica and Clerodendrum trichotomum Extracts In Vitro and In Vivo

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 604 ◽  
Author(s):  
Kiramage Chathuranga ◽  
Myun Soo Kim ◽  
Hyun-Cheol Lee ◽  
Tae-Hwan Kim ◽  
Jae-Hoon Kim ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Drug ◽  
A549 Cells ◽  
Phenolic Glycoside ◽  
Antiviral Effects ◽  
Plantago Asiatica ◽  
Syncytial Virus ◽  
Herb Extract

The herbs Plantago asiatica and Clerodendrum trichotomum have been commonly used for centuries in indigenous and folk medicine in tropical and subtropical regions of the world. In this study, we show that extracts from these herbs have antiviral effects against the respiratory syncytial virus (RSV) in vitro cell cultures and an in vivo mouse model. Treatment of HEp2 cells and A549 cells with a non-cytotoxic concentration of Plantago asiatica or Clerodendrum trichotomum extract significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and also blocked syncytia formation. Interestingly, oral inoculation with each herb extract significantly improved viral clearance in the lungs of BALB/c mice. Based on reported information and a high-performance liquid chromatography (HPLC) analysis, the phenolic glycoside acteoside was identified as an active chemical component of both herb extracts. An effective dose of acteoside exhibited similar antiviral effects as each herb extract against RSV in vitro and in vivo. Collectively, these results suggest that extracts of Plantago asiatica and Clerodendrum trichotomum could provide a potent natural source of an antiviral drug candidate against RSV infection.

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