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 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.

scholarly journals 5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

2020 ◽  
Author(s):  
Yasuteru Sakurai ◽  
Mya Myat Ngwe Tun ◽  
Yohei Kurosaki ◽  
Takaya Sakura ◽  
Daniel Ken Inaoka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dietary Supplement ◽  
Causative Agent ◽  
Levulinic Acid ◽  
Antiviral Drug ◽  
Anticancer Therapy ◽  
Antiviral Effects ◽  
Amino Levulinic Acid ◽  
High Bioavailability

AbstractThe current COVID-19 pandemic requires urgent development of effective therapeutics. 5-amino levulinic acid (5-ALA) is a naturally synthesized amino acid and has been used for multiple purposes including as an anticancer therapy and as a dietary supplement due to its high bioavailability. In this study, we demonstrated that 5-ALA treatment potently inhibited infection of SARS-CoV-2, a causative agent of COVID-19. The antiviral effects could be detected in both human and non-human cells, without significant cytotoxicity. Therefore, 5-ALA is a candidate as an oral antiviral drug for COVID-19.

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 Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1400
Author(s):  
Linda Brunotte ◽  
Shuyu Zheng ◽  
Angeles Mecate-Zambrano ◽  
Jing Tang ◽  
Stephan Ludwig ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Treatment Options ◽  
Combined Treatment ◽  
Antiviral Drug ◽  
Treatment Strategies ◽  
Antiviral Agent ◽  
Life Time ◽  
Adenosine Kinase ◽  
Antiviral Effects

The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast and low-cost approach to the development of new medical treatment options. The direct antiviral agent remdesivir has been reported to exert antiviral activity against SARS-CoV-2. Whereas remdesivir only has a very short half-life time and a bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including the adenosine kinase (ADK) that is moderately expressed in all tissues. The pharmacokinetics of GS-441524 argue for a suitable antiviral drug that can be given to patients with COVID-19. Here, we analyzed the antiviral property of a combined treatment with the remdesivir metabolite GS-441524 and the antidepressant fluoxetine in a polarized Calu-3 cell culture model against SARS-CoV-2. The combined treatment with GS-441524 and fluoxetine were well-tolerated and displayed synergistic antiviral effects against three circulating SARS-CoV-2 variants in vitro in the commonly used reference models for drug interaction. Thus, combinatory treatment with the virus-targeting GS-441524 and the host-directed drug fluoxetine might offer a suitable therapeutic treatment option for 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.

Solubility Enhancement of Poorly Water-Soluble Antifungal Drug Acyclovir by Nanocrystal Formulation Approach

2018 ◽  
Vol 11 (2) ◽  
pp. 4036-4042
Author(s):  
Prakash Goudanavar ◽  
Ankit Acharya ◽  
Vinay C.H
Keyword(s):  
Chemical Interaction ◽  
Research Work ◽  
Antiviral Drug ◽  
In Vitro Release ◽  
Oral Route ◽  
Water Soluble ◽  
Precipitation Method ◽  
Dsc Studies ◽  
Ft Ir

Administration of an antiviral drug, acyclovir via the oral route leads to low and variable bioavailability (15-30%). Therefore, this research work was aimed to enhance bioavailability of acyclovir by nanocrystallization technique. The drug nanocrystals were prepared by anti-solvent precipitation method in which different stabilizers were used. The formed nanocrystals are subjected to biopharmaceutical characterization including solubility, particle size and in-vitro release. SEM studies showed nano-crystals were crystalline nature with sharp peaks. The formulated drug nanocrystals were found to be in the range of 600-900nm and formulations NC7 and NC8 showed marked improvement in dissolution velocity when compared to pure drug, thus providing greater bioavailability. FT-IR and DSC studies revealed the absence of any chemical interaction between drug and polymers used. 

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

scholarly journals Amantadine Inhibits SARS-CoV-2 In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 539
Author(s):  
Klaus Fink ◽  
Andreas Nitsche ◽  
Markus Neumann ◽  
Marica Grossegesse ◽  
Karl-Heinz Eisele ◽  
...  
Keyword(s):  
Influenza A ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Topical Administration ◽  
Counter Measures ◽  
Travel Restrictions ◽  
Drug Treatments ◽  
Intranasal Instillation

Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic under control because people will inadvertently or at a certain degree of restriction severity or duration become incompliant with the regulations. Even if vaccines are approved, the need for antiviral agents against SARS-CoV-2 will persist. However, unequivocal evidence for efficacy against SARS-CoV-2 has not been demonstrated for any of the repurposed antiviral drugs so far. Amantadine was approved as an antiviral drug against influenza A, and antiviral activity against SARS-CoV-2 has been reasoned by analogy but without data. We tested the efficacy of amantadine in vitro in Vero E6 cells infected with SARS-CoV-2. Indeed, amantadine inhibited SARS-CoV-2 replication in two separate experiments with IC50 concentrations between 83 and 119 µM. Although these IC50 concentrations are above therapeutic amantadine levels after systemic administration, topical administration by inhalation or intranasal instillation may result in sufficient amantadine concentration in the airway epithelium without high systemic exposure. However, further studies in other models are needed to prove this hypothesis.

scholarly journals Inhibitory Effect of Sargassum fusiforme and Its Components on Replication of Respiratory Syncytial Virus In Vitro and In Vivo

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 548
Author(s):  
Kiramage Chathuranga ◽  
Asela Weerawardhana ◽  
Niranjan Dodantenna ◽  
Lakmal Ranathunga ◽  
Won-Kyung Cho ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Agent ◽  
Active Components ◽  
Sargassum Fusiforme ◽  
Antiviral Effects ◽  
Improve Life Expectancy ◽  
Rsv Infection ◽  
Syncytial Virus

Sargassum fusiforme, a plant used as a medicine and food, is regarded as a marine vegetable and health supplement to improve life expectancy. Here, we demonstrate that S. fusiforme extract (SFE) has antiviral effects against respiratory syncytial virus (RSV) in vitro and in vivo mouse model. Treatment of HEp2 cells with a non-cytotoxic concentration of SFE significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and syncytium formation. Moreover, oral inoculation of SFE significantly improved RSV clearance from the lungs of BALB/c mice. Interestingly, the phenolic compounds eicosane, docosane, and tetracosane were identified as active components of SFE. Treatment with a non-cytotoxic concentration of these three components elicited similar antiviral effects against RSV infection as SFE in vitro. Together, these results suggest that SFE and its potential components are a promising natural antiviral agent candidate against RSV infection.

Antiviral Therapy of Haemorrhagic Fevers and Arbovirus Infections

1998 ◽  
Vol 3 (2) ◽  
pp. 53-79
Author(s):  
Mike Bray ◽  
John Huggins
Keyword(s):  
New World ◽  
Protective Efficacy ◽  
Rift Valley Fever Virus ◽  
Antiviral Drug ◽  
Drug Effects ◽  
Lassa Fever ◽  
Interferon Α ◽  
Haemorrhagic Fever ◽  
Valley Fever

RNA viruses of the families Arena-, Bunya-, Filo-, Flavi-and Togaviridae cause illness in humans ranging from mild, non-specific febrile syndromes to fulminant, lethal haemorrhagic fever. They are transmitted from animals to humans and from human to human by arthropods, aerosols or contact with body fluids. Antiviral compounds, convalescent plasma and interferon inhibit many of these agents in vitro and in virus-infected animals. Drug or plasma treatment is now in use for several human diseases, and would probably be beneficial for a number of others for which there is only limited treatment experience. Success is linked to early diagnosis and initiation of therapy. Ribavirin is used to treat Lassa fever and haemorrhagic fever with renal syndrome, and would probably be effective for Crimean-Congo haemorrhagic fever and for all New World arenavirus diseases. The value of ribavirin in the early treatment of hantavirus pulmonary syndrome is under evaluation. Convalescent plasma is the therapy of choice for Argentine haemorrhagic fever, and would also probably be effective for other New World arenaviruses and some other infections if a safe supply of plasma could be maintained. Ribavirin and interferon-α have both shown protective efficacy in non-human primates infected with Rift Valley fever virus. No effective therapy has yet been identified for filovirus infections, but results in animal models are encouraging. More clinical research is urgently needed. Even if placebo-controlled drug trials cannot be performed, conscientious reports of the results of therapy in limited numbers of patients can still provide evidence of antiviral drug effects.

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