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Drugs Nov 1979The development of antiviral agents has been hindered by a variety of problems. There are fundamental biological differences between viruses and other infectious agents.... (Review)
Review
The development of antiviral agents has been hindered by a variety of problems. There are fundamental biological differences between viruses and other infectious agents. Viruses are strictly dependent on cellular metabolic processes and possess very limited intrinsic enzyme systems and building blocks which may serve as targets for drugs. Antiviral drugs must also possess the ability to enter the host cell. Viral replication consists of a series of events, each of which can be interfered with, leading to interruption of the viral replication cycle. Currently, the major antiviral agents in therapeutic use are amantadine, idoxuridine and vidarabine. Methisazone and isoprinosine are also used in some areas. Immunoglobulins have some antiviral activity. Immune serum globulin and high titred hepatitis B immune globulin have both been used in prophylaxis of viral hepatitis. However, studies in this area have not been well controlled and results in some areas are conflicting. Interferon appears to be the most exciting antiviral agent yet discovered. However, its potential is limited by its availability, which remains dependent on biological method. Significant progress has been made recently, though, which may lead to the chemical synthesis of interferon and thus to an antiviral agent active against many viruses.
Topics: Amantadine; Antiviral Agents; Ascorbic Acid; Cytarabine; Humans; Idoxuridine; Influenza, Human; Inosine Pranobex; Interferons; Levamisole; Methisazone; Ribavirin; Vidarabine; Virus Replication
PubMed: 92398
DOI: 10.2165/00003495-197918050-00002 -
Viruses Jun 2022Mosquito-borne flavivirus infections affect approximately 400 million people worldwide each year and are global threats to public health. The common diseases caused by... (Review)
Review
Mosquito-borne flavivirus infections affect approximately 400 million people worldwide each year and are global threats to public health. The common diseases caused by such flaviviruses include West Nile, yellow fever, dengue, Zika infection and Japanese encephalitis, which may result in severe symptoms and disorders of multiple organs or even fatal outcomes. Till now, no specific antiviral agents are commercially available for the treatment of the diseases. Numerous strategies have been adopted to develop novel and promising inhibitors against mosquito-borne flaviviruses, including drugs targeting the critical viral components or essential host factors during infection. Research advances in antiflaviviral therapy might optimize and widen the treatment options for flavivirus infection. This review summarizes the current developmental progresses and involved molecular mechanisms of antiviral agents against mosquito-borne flaviviruses.
Topics: Animals; Antiviral Agents; Culicidae; Flavivirus; Flavivirus Infections; Humans; Zika Virus; Zika Virus Infection
PubMed: 35746697
DOI: 10.3390/v14061226 -
AAPS PharmSciTech Nov 2022The present research work attempted to improve the oral bioavailability of the antiviral drug Efavirenz (EFV) using a pharmaceutical cocrystallization technique. EFV...
The present research work attempted to improve the oral bioavailability of the antiviral drug Efavirenz (EFV) using a pharmaceutical cocrystallization technique. EFV comes under BCS-II and has extremely low water solubility, and results in low oral bioavailability. EFV and nicotinamide (NICO) were selected in a (1:1) stoichiometric ratio and efavirenz nicotinamide cocrystal (ENCOC) was prepared through the liquid-assisted grinding method (LAG). The confirmation of the formation of a new solid phase was done through spectroscopic techniques like Fourier transmission infrared (FTIR), Raman, and C solid-state nuclear magnetic resonance (C ssNMR). Thermal techniques like differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and hot stage microscopy (HSM) illustrated the thermal behavior and melting patterns of ENCOC, EFV, and NICO. The X-ray powder diffraction (XRPD) confirms the formation of a new crystalline phase in ENCOC. The Morphology was determined through scanning electron microscopy (FESEM). The results of saturated solubility studies and in vitro drug release studies exhibited 8.9-fold enhancement in solubility and 2.56-fold enhancement in percentage cumulative drug release. The percentage drug content of ENCOC was found higher than 97% and cocrystal exhibits excellent accelerated stability. The oral bioavailability of EFV (C, 799.08 ng/mL) exhibits significant enhancement after cocrystallization (C, 5597.09 ng/mL) than EFV and Efcure®-200 tablet (2896.21 ng/mL). The current work investigates the scalable and cost-effective method for enhancement of physicochemical stability, solubility, and oral bioavailability of an antiviral agent EFV.
Topics: Solubility; Biological Availability; Niacinamide; Antiviral Agents; Pharmaceutical Preparations
PubMed: 36447108
DOI: 10.1208/s12249-022-02467-7 -
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 -
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 -
Nihon Yakurigaku Zasshi. Folia... 2022Remdesivir is a direct-acting antiviral agent that inhibits viral RNA synthesis developed by Gilead Sciences, Inc. in the United States. It has been shown to have...
Remdesivir is a direct-acting antiviral agent that inhibits viral RNA synthesis developed by Gilead Sciences, Inc. in the United States. It has been shown to have antiviral activity against single-stranded RNA viruses, including coronaviruses, in cell culture systems and animal models, and has been developed as a therapeutic agent for Ebola virus infection since 2015. however, to date, it has not been approved in any country. A novel coronavirus infection (COVID-19) was identified in Wuhan, Hubei Province, China in Dec, 2019, and is a respiratory disease characterized by fever, cough, and dyspnea. In severe cases, it may cause serious pneumonia, multi-organ failure and death. Gilead Sciences, Inc. U.S. embarked on the development of COVID-19 as a therapeutic drug, using remdesivir, which has shown in vitro and in vivo antiviral activities against MERS-CoV and SARS-CoV, which are single-stranded RNA coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). The in vitro antiviral activity of remdesivir against SARS-CoV-2, which causes COVID-19, was confirmed and clinical studies were initiated in February 2020. Based on the results of clinical studies conducted by the National Institute of Allergy and Infectious Diseases (NIAID) and Gilead Sciences, Inc. and experience of administration from a compassionate use, an exceptional approval system based on the "Pharmaceuticals and Medical Devices Act" was also approved in Japan as of May 7, 2020 for the indication of "infections caused by SARS-CoV-2." In this article, the background of the development and clinical results of remdesivir are described.
Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; Hemorrhagic Fever, Ebola; Hepatitis C, Chronic; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34980809
DOI: 10.1254/fpj.21058 -
Nephrology Nursing Journal : Journal of... Feb 2003
Review
Topics: Administration, Oral; Antiviral Agents; Biological Availability; Clinical Trials as Topic; Cytomegalovirus Retinitis; Drug Costs; Drug Interactions; Ganciclovir; Humans; Renal Dialysis; Valganciclovir
PubMed: 12674959
DOI: No ID Found -
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 -
Computational Biology and Chemistry Jun 2022The COVID-19 has a worldwide spread, which has prompted concerted efforts to find successful drug treatments. Drug design focused on finding antiviral therapeutic agents...
The COVID-19 has a worldwide spread, which has prompted concerted efforts to find successful drug treatments. Drug design focused on finding antiviral therapeutic agents from plant-derived compounds which may disrupt the attachment of SARS-CoV-2 to host cells is with a pivotal need and role in the last year. Herein, we provide an approach based on drug design methods combined with machine learning approaches to classify and discover inhibitors for COVID-19 from natural products. The spike receptor-binding domain (RBD) was docked with database of 125 ligands. The docking protocol based on several steps was performed within Autodock Vina to identify the high-affinity binding mode and to reveal more insights into interaction between the phytochemicals and the RBD domain. A protein-ligand interaction analyzer has been developed. The drug-likeness properties of explored inhibitors are analyzed in the frame of exploratory data analyses. The developed computational protocol yielded a comprehensive pipeline for predicting the inhibitors to prevent the entry RBD region.
Topics: Antiviral Agents; Biological Products; Drug Evaluation, Preclinical; Humans; Ligands; Molecular Docking Simulation; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19 Drug Treatment
PubMed: 35576744
DOI: 10.1016/j.compbiolchem.2022.107694 -
Molecules (Basel, Switzerland) Nov 2023The results of the most recent investigation of triterpenoid-based antiviral agents namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key... (Review)
Review
The results of the most recent investigation of triterpenoid-based antiviral agents namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong to a series of compounds derived from betulin or betulinic acid, and their synthetic derivative is called bevirimat. A termination of clinical trials of bevirimat in Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid, or other miscellaneous triterpenoids, are relatively rarely involved in a search for a novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.
Topics: Triterpenes; Antiviral Agents; Betulinic Acid; Pentacyclic Triterpenes; Plants
PubMed: 38067449
DOI: 10.3390/molecules28237718