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Journal of Agricultural and Food... Mar 2022In response to the invasion of plant viruses and pathogenic fungi, higher plants produce defensive allelochemicals. Finding candidate varieties of botanical pesticides...
In response to the invasion of plant viruses and pathogenic fungi, higher plants produce defensive allelochemicals. Finding candidate varieties of botanical pesticides based on allelochemicals is one of the important ways to create efficient and green pesticides. Here, a series of camalexin derivatives based on a phytoalexin camalexin scaffold were designed, synthesized, and assessed for their antiviral and fungicidal activities systematically. Most of these camalexin derivatives exhibited better antiviral activities against tobacco mosaic virus (TMV) than the control antiviral agent ribavirin. Under the same test conditions, the anti-TMV activities of compounds , , , and - were found to be equivalent to or better than that of ningnanmycin, an agricultural cytosine nucleoside antibiotic with excellent protective effect. The antiviral mechanism research showed that compound could cause 20S CP disk fusion and disintegration, thus affecting the assembly of virus particles. The results of molecular docking indicate that there were obvious hydrogen bonds between compounds , , and and TMV CP. The binding constants of compounds and to TMV CP were also calculated using fluorescence titration. These camalexin derivatives also presented broad spectrum fungicidal activities, especially for and . In this work, the design, synthesis, structure optimization, and mode of action of camalexin derivatives were carried out progressively. This work provides a reference for using defensive chemical compounds as novel pesticide lead compounds.
Topics: Antiviral Agents; Drug Design; Fungi; Indoles; Molecular Docking Simulation; Sesquiterpenes; Structure-Activity Relationship; Thiazoles; Tobacco Mosaic Virus; Phytoalexins
PubMed: 35179026
DOI: 10.1021/acs.jafc.1c07805 -
Molecules (Basel, Switzerland) Apr 2021The recently emerged COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has adversely affected the whole world. As a significant... (Review)
Review
The recently emerged COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has adversely affected the whole world. As a significant public health threat, it has spread worldwide. Scientists and global health experts are collaborating to find and execute speedy diagnostics, robust and highly effective vaccines, and therapeutic techniques to tackle COVID-19. The ocean is an immense source of biologically active molecules and/or compounds with antiviral-associated biopharmaceutical and immunostimulatory attributes. Some specific algae-derived molecules can be used to produce antibodies and vaccines to treat the COVID-19 disease. Algae have successfully synthesized several metabolites as natural defense compounds that enable them to survive under extreme environments. Several algae-derived bioactive molecules and/or compounds can be used against many diseases, including microbial and viral infections. Moreover, some algae species can also improve immunity and suppress human viral activity. Therefore, they may be recommended for use as a preventive remedy against COVID-19. Considering the above critiques and unique attributes, herein, we aimed to systematically assess algae-derived, biologically active molecules that could be used against this disease by looking at their natural sources, mechanisms of action, and prior pharmacological uses. This review also serves as a starting point for this research area to accelerate the establishment of anti-SARS-CoV-2 bioproducts.
Topics: Antiviral Agents; COVID-19; Carrageenan; Chlorophyta; Humans; Lectins; Phaeophyceae; Polysaccharides; Rhodophyta; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33917694
DOI: 10.3390/molecules26082134 -
International Journal of Pharmaceutics May 2022Unpredictable outbreaks due to respiratory viral infections emphasize the need for new drug delivery strategies to the entire respiratory tract. As viral attack is not...
Unpredictable outbreaks due to respiratory viral infections emphasize the need for new drug delivery strategies to the entire respiratory tract. As viral attack is not limited to a specific anatomic region, antiviral therapy that targets both the upper and lower respiratory tract would be most effective. This study aimed to formulate tamibarotene, a retinoid derivative previously reported to display broad-spectrum antiviral activity against influenza and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), as a novel dual particle size powder formulation that targets both the nasal cavity and the lung by a single route of intranasal administration. Spray freeze drying (SFD) and spray drying (SD) techniques were employed to prepare tamibarotene powder formulations, and cyclodextrin was used as the sole excipient to enhance drug solubility. With the employment of appropriate atomizing nozzles, particles of size above 10 μm and below 5 μm could be produced for nasal and lung deposition, respectively. The aerosol performance of the powder was evaluated using Next Generation Impactor (NGI) coupled with a glass expansion chamber and the powder was dispersed with a nasal powder device. By blending powder of two different particle sizes, a single powder formulation with dual aerosol deposition characteristic in both the nasal and pulmonary regions was produced. The aerosol deposition fractions in the nasal cavity and pulmonary region could be modulated by varying the powder mixing ratio. All dry powder formulations exhibited spherical structures, amorphous characteristics and improved dissolution profile as compared to the unformulated tamibarotene. Overall, a novel dual targeting powder formulation of tamibarotene exhibiting customizable aerosol deposition profile was developed. This exceptional formulation strategy can be adopted to deliver other antimicrobial agents to the upper and lower airways for the prevention and treatment of human respiratory infections.
Topics: Administration, Inhalation; Administration, Intranasal; Aerosols; Antiviral Agents; Dry Powder Inhalers; Humans; Lung; Particle Size; Powders; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35358643
DOI: 10.1016/j.ijpharm.2022.121704 -
Discovery Medicine 2021Remdesivir is a broad-spectrum antiviral agent. With the rapid spread of Coronavirus disease 2019 (COVID-19) globally, remdesivir is taking the spotlight for COVID-19...
Remdesivir is a broad-spectrum antiviral agent. With the rapid spread of Coronavirus disease 2019 (COVID-19) globally, remdesivir is taking the spotlight for COVID-19 treatment. Despite the promising signs of anti-CoV activity in several preclinical and clinical studies, more data of remdesivir in the treatment of COVID-19 is still needed for evaluating its efficacy.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34965372
DOI: No ID Found -
Cepharanthine: a review of the antiviral potential of a Japanese-approved alopecia drug in COVID-19.Pharmacological Reports : PR Dec 2020Cepharanthine (CEP) is a naturally occurring alkaloid derived from Stephania cepharantha Hayata and demonstrated to have unique anti-inflammatory, antioxidative,... (Review)
Review
Cepharanthine (CEP) is a naturally occurring alkaloid derived from Stephania cepharantha Hayata and demonstrated to have unique anti-inflammatory, antioxidative, immunomodulating, antiparasitic, and antiviral properties. Its therapeutic potential as an antiviral agent has never been more important than in combating COVID-19 caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus. Cepharanthine suppresses nuclear factor-kappa B (NF-κB) activation, lipid peroxidation, nitric oxide (NO) production, cytokine production, and expression of cyclooxygenase; all of which are crucial to viral replication and inflammatory response. Against SARS-CoV-2 and homologous viruses, CEP predominantly inhibits viral entry and replication at low doses; and was recently identified as the most potent coronavirus inhibitor among 2406 clinically approved drug repurposing candidates in a preclinical model. This review critically analyzes and consolidates available evidence establishing CEP's potential therapeutic importance as a drug of choice in managing COVID-19 cases.
Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Benzylisoquinolines; COVID-19; Drug Repositioning; Humans; Inflammation; Japan; SARS-CoV-2; Virus Replication; COVID-19 Drug Treatment
PubMed: 32700247
DOI: 10.1007/s43440-020-00132-z -
Bioorganic Chemistry Nov 2023Global coronavirus disease 2019 (COVID-19) pandemic still threatens human health and public safety, and the development of effective antiviral agent is urgently needed....
Global coronavirus disease 2019 (COVID-19) pandemic still threatens human health and public safety, and the development of effective antiviral agent is urgently needed. The SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) are vital proteins in viral replication and promising therapeutic targets. Additionally, PLpro also modulates host immune response by cleaving ubiquitin and interferon-stimulated gene product 15 (ISG15) from ISGylated host proteins. In this report, we identified [1,2]selenazolo[5,4-c]pyridin-3(2H)-one and benzo[d]isothiazol-3(2H)-one as attractive scaffolds of PLpro and Mpro inhibitors. The representative compounds 6c and 7e exhibited excellent PLpro inhibition with percent inhibition of 42.9% and 44.9% at 50 nM, respectively. The preliminary enzyme kinetics experiment and fluorescent labelling experiment results determined that 6c was identified as a covalent PLpro inhibitor, while 7e was a non-covalent inhibitor. Molecular docking and dynamics simulations revealed that 6c and 7e bound to Zn-finger domain of PLpro. Compounds 6c and 7e were also identified to potent Mpro inhibitors, and they exhibited potent antiviral activities in SARS-CoV-2 infected Vero E6 cells, with EC value of 3.9 μM and 7.4 μM, respectively. In addition, the rat liver homogenate half-life of 6c and 7e exceeded 24 h. These findings suggest that 6c and 7e are promising led compounds for further development of PLpro/Mpro dual-target antiviral drugs.
Topics: Animals; Humans; Rats; Antiviral Agents; Coloring Agents; COVID-19; Endopeptidases; Molecular Docking Simulation; Peptide Hydrolases; SARS-CoV-2; Coronavirus Protease Inhibitors; Coronavirus Papain-Like Proteases
PubMed: 37683544
DOI: 10.1016/j.bioorg.2023.106830 -
Viruses Jun 2022Today, hepatitis C virus infection affects up to 1.5 million people per year and is responsible for 29 thousand deaths per year. In the 1970s, the clinical observation... (Review)
Review
Today, hepatitis C virus infection affects up to 1.5 million people per year and is responsible for 29 thousand deaths per year. In the 1970s, the clinical observation of unclear, transfusion-related cases of hepatitis ignited scientific curiosity, and after years of intensive, basic research, the hepatitis C virus was discovered and described as the causative agent for these cases of unclear hepatitis in 1989. Even before the description of the hepatitis C virus, clinicians had started treating infected individuals with interferon. However, intense side effects and limited antiviral efficacy have been major challenges, shaping the aim for the development of more suitable and specific treatments. Before direct-acting antiviral agents could be developed, a detailed understanding of viral properties was necessary. In the years after the discovery of the new virus, several research groups had been working on the hepatitis C virus biology and finally revealed the replication cycle. This knowledge was the basis for the later development of specific antiviral drugs referred to as direct-acting antiviral agents. In 2011, roughly 22 years after the discovery of the hepatitis C virus, the first two drugs became available and paved the way for a revolution in hepatitis C therapy. Today, the treatment of chronic hepatitis C virus infection does not rely on interferon anymore, and the treatment response rate is above 90% in most cases, including those with unsuccessful pretreatments. Regardless of the clinical and scientific success story, some challenges remain until the HCV elimination goals announced by the World Health Organization are met.
Topics: Antiviral Agents; Drug Discovery; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Interferons
PubMed: 35746796
DOI: 10.3390/v14061325 -
Basic & Clinical Pharmacology &... Feb 2021The coronavirus responsible for COVID-19, SARS-CoV-2, utilizes a viral membrane spike protein for host cell entry. For the virus to engage in host membrane fusion,... (Review)
Review
The coronavirus responsible for COVID-19, SARS-CoV-2, utilizes a viral membrane spike protein for host cell entry. For the virus to engage in host membrane fusion, SARS-CoV-2 utilizes the human transmembrane surface protease, TMPRSS2, to cleave and activate the spike protein. Camostat mesylate, an orally available well-known serine protease inhibitor, is a potent inhibitor of TMPRSS2 and has been hypothesized as a potential antiviral drug against COVID-19. In vitro human cell and animal studies have shown that camostat mesylate inhibits virus-cell membrane fusion and hence viral replication. In mice, camostat mesylate treatment during acute infection with influenza, also dependent on TMPRSS2, leads to a reduced viral load. The decreased viral load may be associated with an improved patient outcome. Because camostat mesylate is administered as an oral drug, it may be used in outpatients as well as inpatients at all disease stages of SARS-CoV-2 infection if it is shown to be an effective antiviral agent. Clinical trials are currently ongoing to test whether this well-known drug could be repurposed and utilized to combat the current pandemic. In the following, we will review current knowledge on camostat mesylate mode of action, potential benefits as an antiviral agent and ongoing clinical trials.
Topics: Animals; Antiviral Agents; Drug Repositioning; Esters; Guanidines; Humans; Mice; Patient Safety; Serine Endopeptidases; Serine Proteinase Inhibitors; COVID-19 Drug Treatment
PubMed: 33176395
DOI: 10.1111/bcpt.13533 -
Antiviral Research May 2024Porcine Reproductive and Respiratory Syndrome (PRRS) presents a formidable viral challenge in swine husbandry. Confronting the constraints of existing veterinary...
Porcine Reproductive and Respiratory Syndrome (PRRS) presents a formidable viral challenge in swine husbandry. Confronting the constraints of existing veterinary pharmaceuticals and vaccines, this investigation centers on Caffeic Acid Phenethyl Ester (CAPE) as a prospective clinical suppressant for the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). The study adopts an integrated methodology to evaluate CAPE's antiviral attributes. This encompasses a dual-phase analysis of CAPE's interaction with PRRSV, both in vitro and in vivo, and an examination of its influence on viral replication. Varied dosages of CAPE were subjected to empirical testing in animal models to quantify its efficacy in combating PRRSV infections. The findings reveal a pronounced antiviral potency, notably in prophylactic scenarios. As a predominant component of propolis, CAPE stands out as a promising candidate for clinical suppression, showing exceptional effectiveness in pre-exposure prophylaxis regimes. This highlights the potential of CAPE in spearheading cutting-edge strategies for the management of future PRRSV outbreaks.
Topics: Swine; Animals; Porcine respiratory and reproductive syndrome virus; Prospective Studies; Veterinary Drugs; Porcine Reproductive and Respiratory Syndrome; Virus Replication; Antiviral Agents; Caffeic Acids; Phenylethyl Alcohol
PubMed: 38490343
DOI: 10.1016/j.antiviral.2024.105868 -
Naunyn-Schmiedeberg's Archives of... Oct 2023Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and... (Review)
Review
Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and specific anti-virus medicines' developments remain uncanny. In this century of the biological era, human viruses act predominantly as versatile spreaders. The infection of the present COVID-19 virus is up in the air; blithely, the integument of medicinal chemistry approaches, particularly bioactive derived phytocompounds could be helpful to control those human viruses, recognized in the last 100 years. Indeed, natural products are being used for various therapeutic purposes. The major bioactive phytocompounds are chemically containing coumarin, thiosulfonate, steroid, polysaccharide, tannin, lignin, proanthocyanidin, terpene, quinone, saponin, flavonoid, alkaloid, and polyphenol, that are documented for inhibitory action against several viral infections. Mostly, about 20-30% of plants from tropical or temperate regions are known to have some antiviral activity. This comprehensive analysis of bioactive-derived phytocompounds would represent a significant impact and might be helpful for antiviral research and the current state of viral treatments.
Topics: Humans; Antiviral Agents; COVID-19; SARS-CoV-2
PubMed: 37160482
DOI: 10.1007/s00210-023-02517-2