-
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 -
Drug Research Mar 2022The 2019-nCoV (COVID-19; novel coronavirus disease-2019) outbreak is caused by the coronavirus, and its continued spread is responsible for increasing deaths, social and... (Review)
Review
The 2019-nCoV (COVID-19; novel coronavirus disease-2019) outbreak is caused by the coronavirus, and its continued spread is responsible for increasing deaths, social and economic burden. COVID-19 created a chaotic situation worldwide and claimed the lives of over 5,027,183 and 248,467,363 confirmed cases have been reported so far as per the data published by WHO (World Health Organization) till 5 November 2021. Scientific communities all over the world are toiling to find a suitable therapeutic drug for this deadly disease. Although till date no promising drug has been discovered for this COVID-19. However, as per the WHO, over 102 COVID-19 vaccines are in clinical development and 185 in pre-clinical development. Naturally occurring phytoconstituents possess considerable chemical richness in the form of anti-viral and anti-parasitic potential and have been extensively exploited for the same globally. Still, phytomedicine-based therapies are considered as the best available treatment option to minimize and treat the symptoms of COVID-19 because of the least possible side effects compared to synthetic drugs recommended by the physicians/clinicians. In this review, the use of plant chemicals as a possible therapeutic agent for severe acute respiratory syndrome coronavirus 2 (SARS CoV2) is highlighted with their proposed mechanism of action, which will prove fruitful and effective in finding a cure for this deadly disease.
Topics: Antiviral Agents; COVID-19 Vaccines; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34979573
DOI: 10.1055/a-1697-5365 -
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 -
Therapeutic Drug Monitoring Feb 2022Ganciclovir is the mainstay of therapy for the prophylaxis and treatment of Cytomegalovirus. However, therapy with this antiviral agent is hindered by side effects such... (Review)
Review
BACKGROUND
Ganciclovir is the mainstay of therapy for the prophylaxis and treatment of Cytomegalovirus. However, therapy with this antiviral agent is hindered by side effects such as myelosuppression, which often leads to therapy cessation. Underdosing, as an attempt to prevent side effects, can lead to drug resistance and therapy failure. Therapeutic drug monitoring (TDM) has been used to overcome these problems. The purpose of this narrative review was to give an overview of ganciclovir TDM, available assays, population pharmacokinetic models, and discuss the current knowledge gaps.
METHODS
For this narrative review, a nonsystematic literature search was performed on the PubMed database in April 2021. The following search terms were used: ganciclovir, valganciclovir, pharmacokinetics, pharmacodynamics, population pharmacokinetics, therapeutic drug monitoring, bioassay, liquid chromatography coupled with tandem mass spectrometry, liquid chromatography, chromatography, spectrophotometry, and toxicity. In addition, the reference lists of the included articles were screened.
RESULTS
The most common bioanalysis method identified was liquid chromatography coupled with tandem mass spectrometry. There are different models presenting ganciclovir IC50; however, establishing a pharmacokinetic/pharmacodynamic target for ganciclovir based on preclinical data is difficult because there are no studies combining dynamic drug exposure in relation to inhibition of viral replication. The data on ganciclovir TDM show large interindividual variability, indicating that TDM may play a role in modifying the dose to reduce toxicity and prevent treatment failure related to low concentrations. The main hurdle for implementing TDM is the lack of robust data to define a therapeutic window.
CONCLUSIONS
Although the pharmacokinetics (PK) involved is relatively well-described, both the pharmacodynamics (PD) and pharmacokinetic/pharmacodynamic relationship are not. This is because the studies conducted to date have mainly focused on estimating ganciclovir exposure, and owing to the limited therapeutic options for CMV infections, future studies on ganciclovir are warranted.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Monitoring; Ganciclovir; Humans; Valganciclovir
PubMed: 34610621
DOI: 10.1097/FTD.0000000000000925 -
Drug Discovery Today Oct 2020The Coronavirus Disease 2019 (COVID-19) pandemic is advancing globally, and pharmaceutical prophylaxis is one solution. Here, we propose repositioning chloroquine (CQ)... (Review)
Review
The Coronavirus Disease 2019 (COVID-19) pandemic is advancing globally, and pharmaceutical prophylaxis is one solution. Here, we propose repositioning chloroquine (CQ) as prophylaxis against COVID-19. CQ blocks viral attachment and entry to host cells and demonstrates efficacy against a variety of viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. Furthermore, CQ is safe, inexpensive, and available. Here, we review the antiviral mechanisms of CQ, its in vitro activity against coronaviruses, its pharmacokinetics (PK) and adverse effects, and why it could be more efficacious as a prophylactic rather than as a therapeutic, given the infection dynamics of SARS-CoV-2. We propose two prophylactic regimens based on efficacy and risk considerations. Although it is largely preclinical data that suggest the potential of CQ, properly planned prophylactic trials and further research are urgently needed.
Topics: Animals; Antiviral Agents; COVID-19; Drug Administration Schedule; Drug Repositioning; Humans; Hydroxychloroquine; Patient Safety; Risk Assessment; Risk Factors; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32629169
DOI: 10.1016/j.drudis.2020.06.030 -
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 -
Viruses Feb 2024Influenza A virus (IAV) is the primary causative agent of influenza, colloquially called the flu. Each year, it infects up to a billion people, resulting in hundreds of... (Review)
Review
Influenza A virus (IAV) is the primary causative agent of influenza, colloquially called the flu. Each year, it infects up to a billion people, resulting in hundreds of thousands of human deaths, and causes devastating avian outbreaks with worldwide losses worth billions of dollars. Always present is the possibility that a highly pathogenic novel subtype capable of direct human-to-human transmission will spill over into humans, causing a pandemic as devastating if not more so than the 1918 influenza pandemic. While antiviral drugs for influenza do exist, they target very few aspects of IAV replication and risk becoming obsolete due to antiviral resistance. Antivirals targeting other areas of IAV replication are needed to overcome this resistance and combat the yearly epidemics, which exact a serious toll worldwide. This review aims to summarise the key steps in the IAV replication cycle, along with highlighting areas of research that need more focus.
Topics: Humans; Influenza, Human; Antiviral Agents; Virus Replication; Influenza A virus
PubMed: 38400091
DOI: 10.3390/v16020316 -
Marine Drugs Jul 2021The ongoing pandemic has led to an urgent need for novel drug discovery and potential therapeutics for Sars-CoV-2 infected patients. Although Remdesivir and the... (Review)
Review
The ongoing pandemic has led to an urgent need for novel drug discovery and potential therapeutics for Sars-CoV-2 infected patients. Although Remdesivir and the anti-inflammatory agent dexamethasone are currently on the market for treatment, Remdesivir lacks full efficacy and thus, more drugs are needed. This review was conducted through literature search of PubMed, MDPI, Google Scholar and Scopus. Upon review of existing literature, it is evident that marine organisms harbor numerous active metabolites with anti-viral properties that serve as potential leads for COVID-19 therapy. Inorganic polyphosphates (polyP) naturally found in marine bacteria and sponges have been shown to prevent viral entry, induce the innate immune response, and downregulate human ACE-2. Furthermore, several marine metabolites isolated from diverse sponges and algae have been shown to inhibit main protease (M), a crucial protein required for the viral life cycle. Sulfated polysaccharides have also been shown to have potent anti-viral effects due to their anionic properties and high molecular weight. Likewise, select marine sponges produce bromotyrosines which have been shown to prevent viral entry, replication and protein synthesis. The numerous compounds isolated from marine resources demonstrate significant potential against COVID-19. The present review for the first time highlights marine bioactive compounds, their sources, and their anti-viral mechanisms of action, with a focus on potential COVID-19 treatment.
Topics: Animals; Antiviral Agents; Aquatic Organisms; Humans; Polyphosphates; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34436248
DOI: 10.3390/md19080409 -
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