Antiviral Drugs for Acute Infections
Ontology highlight
ABSTRACT:
SUBMITTER: Powell K
PROVIDER: S-EPMC7149606 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:For the treatment of various viral infections, antiviral drugs may be used. Liquid chromatography-mass spectrometry (LC-MS) with tandem mass spectrometry (MS-MS) operated in selected-reaction monitoring (SRM) mode is the method of choice in quantitative bioanalysis of drugs, e.g., to establish bioavailability, to study pharmacokinetics, and later on possibly for therapeutic drug monitoring. In this study, the fragmentation in MS-MS of small-molecule antiviral drugs against herpes and influenza viruses is reviewed. In this way, insight is gained on the identity of the product ions used in SRM. Fragmentation schemes of antiviral agents are also relevant in the identification of drug metabolites or (forced) degradation products. As information of the fragmentation of antiviral drugs in MS-MS and the identity of the product ions is very much scattered in the scientific literature, it was decided to collect this information and to review it. In this third study, attention is paid to small-molecule antiviral agents used against herpes and influenza virus infections. In addition, some attention is paid to broad-spectrum antiviral agents, that are investigated with respect to their efficacy in challenging virus infections of this century, e.g., involving Ebola, Zika and corona viruses, like SARS-CoV-2, which is causing a world-wide pandemic at this very moment. The review provides fragmentation schemes of ca. 35 antiviral agents. The identity of the product ions used in SRM, i.e., elemental composition and exact-m/z, is tabulated, and more detailed fragmentation schemes are provided.
| S-EPMC7292951 | biostudies-literature
Project description:The infectious microscopic viruses invade living cells to reproduce themselves, and causes chronic infections such as HIV/AIDS, hepatitis B and C, flu, etc. in humans which may lead to death if not treated. Different strategies have been utilized to develop new and superior antiviral drugs to counter the viral infections. The FDA approval of HIV nucleoside reverse transcriptase inhibitor, zidovudine in 1987 boosted the development of antiviral agents against different viruses. Currently, there are a number of combination drugs developed against various viral infections to arrest the activity of same or different viral macromolecules at multiple stages of its life cycle; among which majority are targeted to interfere with the replication of viral genome. Besides these, other type of antiviral molecules includes entry inhibitors, integrase inhibitors, protease inhibitors, interferons, immunomodulators, etc. The antiviral drugs can be toxic to human cells, particularly in case of administration of combination drugs, and on the other hand viruses can grow resistant to the antiviral drugs. Furthermore, emergence of new viruses like Ebola, coronaviruses (SARS-CoV, SARS-CoV-2) emphasizes the need for more innovative strategies to develop better antiviral drugs to fight the existing and the emerging viral infections. Hence, we reviewed the strategic enhancements in developing antiviral drugs for the treatment of different viral infections over the years.
| S-EPMC8055758 | biostudies-literature
Project description:A virus enters a living organism and recruits host metabolism to reproduce its own genome and proteins. The viral infections are intricate and cannot be completely removed through existing antiviral drugs. For example, the herpes, influenza, hepatitis and human immunodeficiency viruses are a few dreadful ones amongst them. Significant studies are needed to understand the viral entry and their growth in host cells to design effective antivirals. This review emphasizes the range of therapeutical antiviral drugs, inhibitors along with vaccines to fight against viral pathogens, especially for combating COVID-19. Moreover, we have provided the basic and in depth information about viral targets, drugs availability, their mechanisms of action, method of prevention of viral diseases and highlighted the significances of anticoagulants, convalescent plasma for COVID-19 treatment, scientific details of airborne transmission, characteristics of antiviral drug delivery using nanoparticles/carriers, nanoemulsions, nanogels, metal based nanoparticles, alike the future nanosystems through nanobubbles, nanofibers, nanodiamonds, nanotraps, nanorobots and eventually, the therapeutic applications of micro- and nanoparticulates, current status for clinical development against COVID-19 together with environmental implications of antivirals, gene therapy etc., which may be useful for repurposing and designing of novel antiviral drugs against various dreadful diseases, especially the SARS-CoV-2 and other associated variants.
| S-EPMC9283561 | biostudies-literature
Project description:Epstein?Barr virus (EBV) infects up to 95% of the adult human population, with primary infection typically occurring during childhood and usually asymptomatic. However, EBV can cause infectious mononucleosis in approximately 35?50% cases when infection occurs during adolescence and early adulthood. Epstein?Barr virus is also associated with several B-cell malignancies including Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease. A number of antiviral drugs have proven to be effective inhibitors of EBV replication, yet have resulted in limited success clinically, and none of them has been approved for treatment of EBV infections.
| S-EPMC6025560 | biostudies-literature
Project description:Thirty years ago, just three drugs were available for the treatment of viral infections, but now more than forty have been approved. What have been the guiding principles in these achievements and what might the future hold for antiviral drug development? Supplementary information The online version of this article (doi:10.1038/nrd2485) contains supplementary material, which is available to authorized users.
| S-EPMC7097450 | biostudies-literature
Project description:(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.
| S-EPMC7761982 | biostudies-literature
Project description:Caliciviridae are human or non-human pathogenic viruses with a high diversity. Some members of the Caliciviridae, i.e. human pathogenic norovirus or rabbit hemorrhagic disease virus (RHDV), are worldwide emerging pathogens. The norovirus is the major cause of viral gastroenteritis worldwide, accounting for about 85% of the outbreaks in Europe between 1995 and 2000. In the United States, 25 million cases of infection are reported each year. Since its emergence in 1984 as an agent of fatal hemorrhagic diseases in rabbits, RHDV has killed millions of rabbits and has been dispersed to all of the inhabitable continents. In view of their successful and apparently increasing emergence, the development of antiviral strategies to control infections due to these viral pathogens has now become an important issue in medicine and veterinary medicine. Antiviral strategies have to be based on an understanding of the epidemiology, transmission, clinical symptoms, viral replication and immunity to infection resulting from infection by these viruses. Here, we provide an overview of the mechanisms underlying calicivirus infection, focusing on the molecular aspects of replication in the host cell. Recent experimental data generated through an international collaboration on structural biology, virology and drug design within the European consortium VIZIER is also presented. Based on this analysis, we propose antiviral strategies that may significantly impact on the epidemiological characteristics of these highly successful viral pathogens.
| S-EPMC7114105 | biostudies-literature
Project description:Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to contain transmission. This poses the question of whether preparedness for a future pandemic should include plans to use antiviral drugs to mitigate transmission.Simulations using a standard transmission model that allows for infected arrivals and delayed vaccination show that attempts to contain transmission require relatively few antiviral doses. In contrast, persistent use of antiviral drugs when the reproduction number remains above 1 use very many doses and are unlikely to reduce the eventual attack rate appreciably unless the stockpile is very large. A second model, in which the community has a household structure, shows that the effectiveness of a strategy of dispensing antiviral drugs to infected households decreases rapidly with time delays in dispensing the antivirals. Using characteristics of past pandemics it is estimated that at least 80% of primary household cases must present upon show of symptoms to have a chance of containing transmission by dispensing antiviral drugs to households. To determine data needs, household outbreaks were simulated with 50% receiving antiviral drugs early and 50% receiving antiviral drugs late. A test to compare the size of household outbreaks indicates that at least 100-200 household outbreaks need to be monitored to find evidence that antiviral drugs can mitigate transmission of the newly emerged virus.Use of antiviral drugs in an early attempt to contain transmission should be part of preparedness plans for a future influenza pandemic. Data on the incidence of the first 350 cases and the eventual attack rates of the first 200 hundred household outbreaks should be used to estimate the initial reproduction number R and the effectiveness of antiviral drugs to mitigate transmission. Use of antiviral drugs to mitigate general transmission should cease if these estimates indicate that containment of transmission is unlikely.
| S-EPMC3065466 | biostudies-literature
Project description:Background:The relative risk of acute kidney injury (AKI) following different infections, and whether angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) modify the risk, is unclear. We aimed to determine the risks of hospital admission with AKI following infections (urinary tract infection [UTI], lower respiratory tract infection [LRTI], and gastroenteritis) among users of antihypertensive drugs. Methods:We used UK electronic health records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database. We identified adults initiating ACEIs/ARBs or alternative antihypertensive therapy (?-blockers, calcium channel blockers, or thiazide diuretics) between April 1997 and March 2014 with at least 1 year of primary care registration prior to first prescription, who had a hospital admission for AKI, and who had a primary care record for incident UTI, LRTI, or gastroenteritis. We used a self-controlled case series design to calculate age-adjusted incidence rate ratios (IRRs) for AKI during risk periods following acute infection relative to noninfected periods (baseline). Results:We identified 10,219 eligible new users of ACEIs/ARBs or other antihypertensives with an AKI record. Among these, 2,012 had at least one record for a UTI during follow-up, 2,831 had a record for LRTI, and 651 had a record for gastroenteritis. AKI risk was higher following infection than in baseline noninfectious periods. The rate ratio was highest following gastroenteritis: for the period 1-7 days postinfection, the IRR for AKI following gastroenteritis was 43.4 (95% CI=34.0-55.5), compared with 6.0 following LRTI (95% CI=5.0-7.3), and 9.3 following UTI (95% CI=7.8-11.2). Increased risks were similar for different antihypertensives. Conclusion:Acute infections are associated with substantially increased transient AKI risk among antihypertensive users, with the highest risk after gastroenteritis. The increase in relative risk is not greater among users of ACEIs/ARBs compared with users of other antihypertensives.
| S-EPMC5796801 | biostudies-literature
Project description:Antiviral drugs are a class of medicines particularly used for the treatment of viral infections. Drugs that combat viral infections are called antiviral drugs. Viruses are among the major pathogenic agents that cause number of serious diseases in humans, animals and plants. Viruses cause many diseases in humans, from self resolving diseases to acute fatal diseases. Developing strategies for the antiviral drugs are focused on two different approaches: Targeting the viruses themselves or the host cell factors. Antiviral drugs that directly target the viruses include the inhibitors of virus attachment, inhibitors of virus entry, uncoating inhibitors, polymerase inhibitors, protease inhibitors, inhibitors of nucleoside and nucleotide reverse transcriptase and the inhibitors of integrase. The inhibitors of protease (ritonavir, atazanavir and darunavir), viral DNA polymerase (acyclovir, tenofovir, valganciclovir and valacyclovir) and of integrase (raltegravir) are listed among the Top 200 Drugs by sales during 2010s. Still no effective antiviral drugs are available for many viral infections. Though, there are a couple of drugs for herpesviruses, many for influenza and some new antiviral drugs for treating hepatitis C infection and HIV. Action mechanism of antiviral drugs consists of its transformation to triphosphate following the viral DNA synthesis inhibition. An analysis of the action mechanism of known antiviral drugs concluded that they can increase the cell's resistance to a virus (interferons), suppress the virus adsorption in the cell or its diffusion into the cell and its deproteinisation process in the cell (amantadine) along with antimetabolites that causes the inhibition of nucleic acids synthesis. This review will address currently used antiviral drugs, mechanism of action and antiviral agents reported against COVID-19.
| S-EPMC7975490 | biostudies-literature