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Pharmacology & Therapeutics May 2020Favipiravir has been developed as an anti-influenza drug and licensed as an anti-influenza drug in Japan. Additionally, favipiravir is being stockpiled for 2 million... (Review)
Review
Favipiravir has been developed as an anti-influenza drug and licensed as an anti-influenza drug in Japan. Additionally, favipiravir is being stockpiled for 2 million people as a countermeasure for novel influenza strains. This drug functions as a chain terminator at the site of incorporation of the viral RNA and reduces the viral load. Favipiravir cures all mice in a lethal influenza infection model, while oseltamivir fails to cure the animals. Thus, favipiravir contributes to curing animals with lethal infection. In addition to influenza, favipiravir has a broad spectrum of anti-RNA virus activities in vitro and efficacies in animal models with lethal RNA viruses and has been used for treatment of human infection with life-threatening Ebola virus, Lassa virus, rabies, and severe fever with thrombocytopenia syndrome. The best feature of favipiravir as an antiviral agent is the apparent lack of generation of favipiravir-resistant viruses. Favipiravir alone maintains its therapeutic efficacy from the first to the last patient in an influenza pandemic or an epidemic lethal RNA virus infection. Favipiravir is expected to be an important therapeutic agent for severe influenza, the next pandemic influenza strain, and other severe RNA virus infections for which standard treatments are not available.
Topics: Amides; Animals; Antiviral Agents; Humans; Influenza, Human; Pyrazines; RNA Virus Infections
PubMed: 32097670
DOI: 10.1016/j.pharmthera.2020.107512 -
Journal of Agricultural and Food... Jul 2022Coat proteins (CPs) of RNA plant viruses play a pivotal role in virus particle assembly, vector transmission, host identification, RNA replication, and intracellular and... (Review)
Review
Coat proteins (CPs) of RNA plant viruses play a pivotal role in virus particle assembly, vector transmission, host identification, RNA replication, and intracellular and intercellular movement. Numerous compounds targeting CPs have been designed, synthesized, and screened for their antiviral activities. This review is intended to fill a knowledge gap where a comprehensive summary is needed for antiviral agent discovery based on plant viral CPs. In this review, major achievements are summarized with emphasis on plant viral CPs as biochemical targets and action mechanisms of antiviral agents. This review hopefully provides new insights and references for the further development of new safe and effective antiviral pesticides.
Topics: Antiviral Agents; Capsid Proteins; Plant Viruses; Plants; RNA; Virus Replication
PubMed: 35830295
DOI: 10.1021/acs.jafc.2c02888 -
Molecules (Basel, Switzerland) Jan 2021Subacute sclerosing panencephalitis (SSPE) is a late-onset, intractable, and fatal viral disease caused by persistent infection of the central nervous system by a mutant... (Review)
Review
Subacute sclerosing panencephalitis (SSPE) is a late-onset, intractable, and fatal viral disease caused by persistent infection of the central nervous system by a mutant strain of the measles virus. Ribavirin intracerebroventricular therapy has already been administered to several SSPE patients in Japan based on fundamental and clinical research findings from our group, with positive therapeutic effects reported in some patients. However, the efficacy of this treatment approach has not been unequivocally established. Hence, development of more effective therapeutic methods using new antiviral agents is urgently needed. This review describes the current status of SSPE treatment and research, highlighting promising approaches to the development of more effective therapeutic methods.
Topics: Animals; Antiviral Agents; Drug Development; Humans; Subacute Sclerosing Panencephalitis
PubMed: 33467470
DOI: 10.3390/molecules26020427 -
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 -
Drug Design, Development and Therapy 2022The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19... (Review)
Review
The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19 patients. This review evaluated a battery of antiviral compounds and their effectiveness in the treatment of COVID-19 since the beginning of the pandemic. Remdesivir is the only antiviral approved by the EMA and FDA for the treatment of SARS-CoV-2 infection. This work extensively reviews remdesivir data generated from clinical trials and observational studies, paying attention to the most recent data, and focusing on outcomes to give readers a more comprehensive understanding of the results. This review also discusses the recommendations issued by official bodies during the pandemic in the light of the current knowledge. The use of remdesivir in the treatment of SARS-CoV-2 infection is justified because a virus is the causative agent that triggers the inflammatory responses and its consequences. More trials are needed to improve the management of this disease.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; SARS-CoV-2; Virus Replication; COVID-19 Drug Treatment
PubMed: 35370401
DOI: 10.2147/DDDT.S356951 -
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 -
Molecular Pharmaceutics Jun 2021The ongoing pandemic of global concern has killed about three million humans and affected around 151 million people worldwide, as of April 30, 2021. Although recently... (Review)
Review
The ongoing pandemic of global concern has killed about three million humans and affected around 151 million people worldwide, as of April 30, 2021. Although recently approved vaccines for COVID-19 are engendering hope, finding new ways to cure the viral pandemic is still a quest for researchers worldwide. Major pandemics in history have been of viral origin, such as SARS, MERS, H1NI, Spanish flu, and so on. A larger emphasis has been on discovering potential vaccines, novel antiviral drugs, and agents that can mitigate the viral infection symptoms; however, a relatively new area, RNA interference (RNAi), has proven effective as an antiviral agent. The RNAi phenomenon has been largely exploited to cure cancer, neurodegenerative diseases, and some rare diseases. The U.S. Food and Drug Administration has recently approved three siRNA products for human use that garner significant hope in siRNA therapeutics for coronaviruses. There have been some commentaries and communications addressing this area. We have summarized and illustrated the significance and the potential of the siRNA therapeutics available as of April 30, 2021 to combat the ongoing viral pandemic and the emerging new variants such as B.1.1.7 and B.1.351. Numerous successful studies and several investigations to address the clinical application of siRNA therapeutics provide great hope in this field. This seminal Review describes the significance of siRNA-based therapy to treat diverse viral infections in addition to the current coronavirus challenge. In addition, we have thoroughly reviewed the patents approved for coronaviruses, the major challenges in siRNA therapy, and the potential approaches to address them, followed by innovation and prospects.
Topics: Antiviral Agents; COVID-19; Clinical Trials as Topic; Drug Approval; Drug Evaluation, Preclinical; History, 20th Century; History, 21st Century; Humans; Mutation; Pandemics; Patents as Topic; RNA, Small Interfering; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33945284
DOI: 10.1021/acs.molpharmaceut.0c01239