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Current Organic Synthesis 2023Plant diseases caused by viruses and pathogens have posed a serious threat to global agricultural production and are difficult to control. Natural products have always...
BACKGROUND
Plant diseases caused by viruses and pathogens have posed a serious threat to global agricultural production and are difficult to control. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. The natural product resveratrol was found to have good antiviral activity against the tobacco mosaic virus (TMV) and fungicidal activities against 14 kinds of phytopathogenic fungi.
OBJECTIVE
The aim of this work was to design, synthesize a series of derivatives of resveratrol, and evaluate their antiviral and fungicidal activities systematically.
METHODS
Novel resveratrol sulfonate derivatives were prepared by a convenient synthesis method from resveratrol, alkyl sulfonyl chloride, aryl sulfonyl chloride, and heterocyclic sulfonyl chloride. Their structures were also identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS).
RESULTS
Most of the targets were obtained at a high yield. Compounds I-2, I-5, I-10, II-2, and II-4, with excellent antiviral activities, showed higher anti-TMV activities than those of lead compounds and commercial ribavirin (inhibitory rates of 38, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively). In particular, compounds I-5, I-10, II-2, and II-4 displayed similar inhibitory effects as ningnanmycin (inhibitory rates of 54, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best antiviral agent at present, thereby emerging as new antiviral pilot compounds. Further fungicidal activity tests showed that resveratrol derivatives also displayed broad-spectrum fungicidal activities.
CONCLUSION
The anti-TMV activities of these compounds were discovered for the first time. Some of these simply structured compounds showed higher TMV inhibitory effects than ribavirin. The current study provided valuable insights into the antiviral and fungicidal activities of resveratrol derivatives, but more modification of the structure should be conducted.
Topics: Antiviral Agents; Ribavirin; Structure-Activity Relationship; Molecular Structure; Resveratrol; Fungicides, Industrial; Alkaloids; Fungi; Tobacco Mosaic Virus; Biological Products
PubMed: 36200163
DOI: 10.2174/1570179420666221005124445 -
Virus Research Jan 2022Due to the lack of an adaptive immune system, insects rely on innate immune mechanisms to fight against pathogenic infections. Two major innate immune pathways, Toll and...
Due to the lack of an adaptive immune system, insects rely on innate immune mechanisms to fight against pathogenic infections. Two major innate immune pathways, Toll and IMD, orchestrate anti-pathogen responses by regulating the expression of antimicrobial peptide (AMP) genes. Although the antifungal or antibacterial function of AMPs has been well characterized, the antiviral role of AMPs in insects remains largely unclear. Periplaneta americana (P. americana), or the American cockroach, is used in traditional Chinese medicine as an antiviral agent; however, the underlying mechanism of action of P. americana extracts is unclear. Our previous study showed that the P. americana genome encodes multiple antimicrobial peptide genes. Based on these data, we predicted five novel P. americana defensins (PaDefensins) and analyzed their primary structure, secondary structure, and physicochemical properties. The putative antiviral, antifungal, antibacterial, and anticancer activities suggested that PaDefensin5 is a desirable therapeutic candidate against viral diseases. As the first experimental evidence of the antiviral effects of insect defensins, we also showed the antiviral effect of PaDefensin5 in Drosophila Kc cells and Drosophila embryos in vivo . In conclusion, results of both in silico predictions and subsequent antiviral experiments suggested PaDefensin5 a promising antiviral drug.
Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Antiviral Agents; Computational Biology; Defensins; Drosophila; Insecta; Periplaneta
PubMed: 34785275
DOI: 10.1016/j.virusres.2021.198627 -
Clinical Infectious Diseases : An... Oct 2020Baloxavir marboxil (formerly S-033188) is a prodrug of baloxavir acid (S-033447) and inhibits cap-dependent endonuclease, an essential protein involved in the initiation... (Review)
Review
Baloxavir marboxil (formerly S-033188) is a prodrug of baloxavir acid (S-033447) and inhibits cap-dependent endonuclease, an essential protein involved in the initiation of viral transcription by cleaving capped mRNA bound to PB2. Its adverse event profile is comparable to oseltamivir but is still vulnerable to resistance. The single-dose baloxavir marboxil is an appealing antiviral regimen for the treatment of influenza among outpatients when compared with longer, twice-daily regimens of oral and inhaled neuraminidase inhibitors. This review focuses on the mode of action, antiviral activity, pharmacokinetics, clinical indications, and safety profiles of this drug. Considerations for formulary addition and its place in therapy are also discussed.
Topics: Antiviral Agents; Dibenzothiepins; Humans; Influenza, Human; Morpholines; Pyridones; Triazines
PubMed: 32020174
DOI: 10.1093/cid/ciaa107 -
Bioorganic & Medicinal Chemistry Oct 2022Oxetanocin A (Oxt-A), a novel oxetanosyl N-glycoside nucleoside, was isolated from Bacillus megaterium in 1986. It carries an oxetane ring on the sugar moiety of the... (Review)
Review
Oxetanocin A (Oxt-A), a novel oxetanosyl N-glycoside nucleoside, was isolated from Bacillus megaterium in 1986. It carries an oxetane ring on the sugar moiety of the nucleoside scaffold, which contributes to differences in its structure from those of common tetrahydrofuranyl-based nucleosides. In view of the unique 3D-spatial framework, the complete synthesis of Oxt-A has been achieved by multiple research groups. The pharmacological properties of this natural product have also been broadly investigated by pharmacists and chemists since its discovery. Notably, the potential antiviral effect of Oxt-A has captured attention of researchers in the field of antiviral agent development. Furthermore, epidemic outbreaks caused by viruses have been stimulating the preparation and modification of various Oxt-A analogs over the past few decades. However, none of the studies have overviewed the antiviral efficacies of this naturally occurring scaffold yet. Thus, the present review summarizes the synthesis, structural modification, and antiviral activities of Oxt-A and its derivatives. We believe that these comprehensive descriptions will provide a novel perspective for the discovery of antivirus drugs with well-improved performance and pave newer paths for combating sudden public health issues triggered by viruses in the future.
Topics: Adenine; Antiviral Agents; Biological Products; Nucleosides; Sugars
PubMed: 36054994
DOI: 10.1016/j.bmc.2022.116968 -
Journal of Biomaterials Science.... Jan 2022The limited time indorsed to face the COVID-19 emergency and large number of deaths across the globe, poses an unrelenting challenge to find apt therapeutic approaches.... (Review)
Review
The limited time indorsed to face the COVID-19 emergency and large number of deaths across the globe, poses an unrelenting challenge to find apt therapeutic approaches. However, lead candidate selection to phase III trials of new chemical entity is a time-consuming procedure, and not feasible in pandemic, such as the one we are facing. Drug repositioning, an exploration of existing drug for new therapeutic use, could be an effective alternative as it allows fast-track estimation in phase II-III trials, or even forthright compassionate use. Although, drugs repurposed for COVID-19 pandemic are commercially available, yet the evaluation of their safety and efficacy is tiresome and painstaking. In absence of any specific treatment the easy alternatives such as over the counter products, phytotherapies and home remedies have been largely adopted for prophylaxis and therapy as well. In recent years, it has been demonstrated that several pharmaceutical excipients possess antiviral properties making them prospective candidates against SARS-CoV-2. This review highlights the mechanism of action of various antiviral excipients and their propensity to act against SARs-CoV2. Though, repurposing of pharmaceutical excipients against COVID-19 has the edge over therapeutic agents in terms of safety, cost and fast-track approval trial burdened, this hypothesis needs to be experimentally verified for COVID-19 patients.
Topics: Antiviral Agents; Drug Repositioning; Excipients; Humans; Pandemics; Prospective Studies; RNA, Viral; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34464232
DOI: 10.1080/09205063.2021.1975020 -
Food and Environmental Virology Jun 2022The use of natural resources for the prevention and treatment of diseases considered fatal to humanity has evolved. Several medicinal plants have nutritional and... (Review)
Review
The use of natural resources for the prevention and treatment of diseases considered fatal to humanity has evolved. Several medicinal plants have nutritional and pharmacological potential in the prevention and treatment of viral infections, among them, turmeric, which is recognized for its biological properties associated with curcuminoids, mainly represented by curcumin, and found mostly in rhizomes. The purpose of this review was to compile the pharmacological activities of curcumin and its analogs, aiming at stimulating their use as a therapeutic strategy to treat infections caused by RNA genome viruses. We revisited its historical application as an anti-inflammatory, antioxidant, and antiviral agent that combined with low toxicity, motivated research against viruses affecting the population for decades. Most findings concentrate particularly on arboviruses, HIV, and the recent SARS-CoV-2. As one of the main conclusions, associating curcuminoids with nanomaterials increases solubility, bioavailability, and antiviral effects, characterized by blocking the entry of the virus into the cell or by inhibiting key enzymes in viral replication and transcription.
Topics: Antiviral Agents; Curcumin; Diarylheptanoids; Humans; RNA; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35352306
DOI: 10.1007/s12560-022-09514-3 -
Molecules (Basel, Switzerland) Mar 2023Pesticides are essential for the development of agriculture. It is urgent to develop green, safe and efficient pesticides. Bisindole alkaloids have unique and concise...
Pesticides are essential for the development of agriculture. It is urgent to develop green, safe and efficient pesticides. Bisindole alkaloids have unique and concise structures and broad biological activities, which make them an important leading skeleton in the creation of new pesticides. In this work, we synthesized bisindole alkaloid barakacin in a simple seven-step process, and simultaneously designed and synthesized a series of its derivatives. Biological activity research indicated that most of these compounds displayed good antiviral activities against tobacco mosaic virus (TMV). Among them, compound exerted a superior inhibitory effect in comparison to commercially available antiviral agent ribavirin, and could be expected to become a novel antiviral candidate. Molecular biology experiments and molecular docking research found that the potential target of compound was TMV coat protein (CP). These compounds also showed broad-spectrum anti-fungal activities against seven kinds of plant fungi.
Topics: Antiviral Agents; Structure-Activity Relationship; Molecular Docking Simulation; Fungicides, Industrial; Ribavirin; Tobacco Mosaic Virus; Alkaloids; Drug Design
PubMed: 37049795
DOI: 10.3390/molecules28073032 -
Journal of Drugs in Dermatology : JDD Jul 2023
Topics: Humans; Antiviral Agents; Nitric Oxide; Dermatologists
PubMed: 37410052
DOI: No ID Found -
Cytometry. Part B, Clinical Cytometry Jan 2021With the morbidity and mortality associated with the COVID-19 pandemic that we are witnessing this year, the risks posed by emerging viral diseases to global health are... (Review)
Review
With the morbidity and mortality associated with the COVID-19 pandemic that we are witnessing this year, the risks posed by emerging viral diseases to global health are all too obvious. This pandemic highlights the importance of antiviral drug discovery, which targets emerging viral pathogens, as well as existing pathogenic viruses that undergo continuous evolution. Drug discovery and development is a long and resource intensive process; however, the use of biomarkers can accelerate clinical development of antivirals by providing information regarding diagnosis of specific viral infections, status of infection, potential safety parameters, and antiviral responses. In clinical practice, many of the biomarkers initially utilized to support clinical development are also used for patient care. While viral load is a standard and essential biomarker used to detect the desired viral suppression induced by an antiviral agent, it has become apparent that additional biomarkers, whether related to the virus, the host or as a consequence of the drug's mechanistic effects, are also important for monitoring clinical outcomes associated with an antiviral therapy. This review summarizes the biomarkers used in the clinical development (as well as in clinical practice, where appropriate) of antiviral therapies for hepatitis C virus, hepatitis B virus, human immunodeficiency virus, and severe acute respiratory syndrome coronavirus 2.
Topics: Animals; Antiviral Agents; Biomarkers; COVID-19; Clinical Trials as Topic; Humans; SARS-CoV-2; Virus Diseases; COVID-19 Drug Treatment
PubMed: 34542933
DOI: 10.1002/cyto.b.21974 -
Anti-inflammatory & Anti-allergy Agents... 2023The role of herbal medicines in the treatment of viruses and the identification of potential antiviral drugs has been the focus of researchers for decades. The control... (Review)
Review
The role of herbal medicines in the treatment of viruses and the identification of potential antiviral drugs has been the focus of researchers for decades. The control and treatment of viral diseases are very important due to the evolution of viruses and the emergence of new viruses compared to other pathogens such as fungi and bacteria. (AM) is a significant medicinal plant. The potential use of this plant and its chemical components in the treatment of inflammatory illnesses and viral diseases has been vigorously researched recently. polysaccharides (APS) make up the majority of AM's ingredients. The main mechanisms of the antiviral effect of APS have been investigated in some studies. The results of these studies show that APS can exert its antiviral effect by enhancing type I IFN signaling, inhibiting the expression of Bax and Caspase-3 proteins in the apoptosis pathway, and other antiviral mechanisms such as anti-inflammatory activities. The most well-known inflammatory products of APS's antiviral effects are B-cell proliferation, antibody products, nuclear factor-kappa B (NF-κB), and IL(s). Although it has a known effectiveness, there are some limitations to this substance's use as medicine. The use of nanotechnology is removing these limitations and its ability to be used as an anti-virus agent. The purpose of this review is to emphasize the role of AM, especially APS, in controlling inflammatory pathways in the treatment of viral infections. With the emergence of these herbal medications, a new path has been opened in the control and treatment of viral infections.
Topics: Astragalus propinquus; Signal Transduction; Anti-Inflammatory Agents; Plants, Medicinal; Antiviral Agents; Virus Diseases; Polysaccharides
PubMed: 38115620
DOI: 10.2174/0118715230280333231207114927