scholarly journals Tilorone, a Broad-Spectrum Antiviral for Emerging Viruses

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Sean Ekins ◽  
Peter B. Madrid
Keyword(s):  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Ebola Virus ◽  
Middle Eastern ◽  
Emerging Viruses ◽  
Small Molecule Compound ◽  
The Russian Federation ◽  
Synthetic Small Molecule

ABSTRACT Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV).

scholarly journals Tilorone: A Broad-Spectrum Antiviral For Emerging Viruses

2020 ◽  
Author(s):  
Sean Ekins ◽  
Peter B. Madrid
Keyword(s):  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Ebola Virus ◽  
Middle Eastern ◽  
Emerging Viruses ◽  
Small Molecule Compound ◽  
The Russian Federation ◽  
Synthetic Small Molecule

AbstractTilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola Virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).

scholarly journals Tilorone: A Broad-Spectrum Antiviral For Emerging Viruses

2020 ◽  
Author(s):  
Sean Ekins ◽  
Peter Madrid
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Middle Eastern ◽  
Emerging Viruses

Tilorone demonstrates in vitro antiviral activity against Chikungunya virus (CHIK) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).

A review on Remdesivir: A broad-spectrum antiviral molecule for possible COVID-19 treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Jabeena Khazir ◽  
Tariq Maqbool ◽  
Bilal Ahmad Mir
Keyword(s):  
Clinical Trials ◽  
Broad Spectrum ◽  
Ebola Virus ◽  
Controlled Trial ◽  
In Vivo Studies ◽  
Therapeutic Drug ◽  
Viral Agent ◽  
Double Blind

: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was identified to have emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering has led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials researchers worldwide are currently using available conventional therapeutic drugs with potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to show promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID-19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.

scholarly journals Defective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes

2021 ◽  
Vol 17 (2) ◽  
pp. e1009110
Author(s):  
Laura I. Levi ◽  
Veronica V. Rezelj ◽  
Annabelle Henrion-Lacritick ◽  
Diana Erazo ◽  
J Boussier ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Rna Virus ◽  
Viral Genomes ◽  
Mosquito Cells ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

Defective viral genomes (DVGs) are truncated and/or rearranged viral genomes produced during virus replication. Described in many RNA virus families, some of them have interfering activity on their parental virus and/or strong immunostimulatory potential, and are being considered in antiviral approaches. Chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes spp. that infected millions of humans in the last 15 years. Here, we describe the DVGs arising during CHIKV infection in vitro in mammalian and mosquito cells, and in vivo in experimentally infected Aedes aegypti mosquitoes. We combined experimental and computational approaches to select DVG candidates most likely to have inhibitory activity and showed that, indeed, they strongly interfere with CHIKV replication both in mammalian and mosquito cells. We further demonstrated that some DVGs present broad-spectrum activity, inhibiting several CHIKV strains and other alphaviruses. Finally, we showed that pre-treating Aedes aegypti with DVGs prevented viral dissemination in vivo.

scholarly journals The Use of Antimalarial Drugs against Viral Infection

2020 ◽  
Vol 8 (1) ◽  
pp. 85 ◽  
Author(s):  
Sarah D’Alessandro ◽  
Diletta Scaccabarozzi ◽  
Lucia Signorini ◽  
Federica Perego ◽  
Denise P. Ilboudo ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Viral Infections ◽  
Antimalarial Drugs ◽  
Drug Resistant ◽  
Emerging Viruses ◽  
Antimicrobial Drugs ◽  
Artemisinin Derivatives ◽  
Antiviral Activities

In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.

scholarly journals Broad-Spectrum In Vitro Activity and In Vivo Efficacy of the Antiviral Protein Griffithsin against Emerging Viruses of the Family Coronaviridae

2010 ◽  
Vol 84 (10) ◽  
pp. 5456-5456 ◽  
Author(s):  
B. R. O'Keefe ◽  
B. Giomarelli ◽  
D. L. Barnard ◽  
S. R. Shenoy ◽  
P. K. S. Chan ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Emerging Viruses ◽  
Antiviral Protein ◽  
In Vivo Efficacy ◽  
The Family

scholarly journals Aglycone polyether ionophores as broad-spectrum agents inhibit multiple enveloped viruses including SARS-CoV-2 in vitro and successfully cure JEV infected mice

2020 ◽  
Author(s):  
Jia-Qi Li ◽  
Minjian Huang ◽  
Ya-Nan Zhang ◽  
Ran Liu ◽  
Zhe-Rui Zhang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Mechanistic Studies ◽  
Global Risk ◽  
Enveloped Viruses ◽  
Zoonotic Viruses ◽  
Full Protection

AbstractInfections with zoonotic viruses, such as flaviviruses, influenza virus, and the SARS-CoV-2 pandemic coronavirus constitute an increasing global risk. Hence, an urgent need exists for the development of broad-spectrum antivirals to prevent such outbreaks. Here, we show that the maduramycin and CP-80,219 aglycone polyether ionophores exhibit effective broad-spectrum antiviral activity, against various viruses, including Japanese encephalitis virus (JEV), Dengue virus (DENV), Zika virus (ZIKV), and Chikungunya virus (CHIKV), while also exhibiting promising activity against PR8 influenza virus and SARS-CoV-2. Moreover, liposome-encapsulated maduramycin and CP-80,219 provide full protection for mice from infection with JEV in vivo. Mechanistic studies suggest that aglycone polyether ionophores primarily inhibit the viral replication step without blocking endosome acidification to promote the fusion between viral and cellular membranes. The successful application of liposomes containing aglycone polyether ionophores in JEV-infected mice offers hope to the development of broad-spectrum antiviral drugs like penicillin back to 1940s.

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 Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 439
Author(s):  
Christopher G. Bunick ◽  
Jonette Keri ◽  
S. Ken Tanaka ◽  
Nika Furey ◽  
Giovanni Damiani ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Antibiotic Use ◽  
In Vivo Studies ◽  
Infection Model ◽  
Severe Acne ◽  
Rat Paw Edema ◽  
Infection And Inflammation

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.

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