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Molecules (Basel, Switzerland) Jul 2023The goal of an antiviral agent research is to find an antiviral drug that reduces viral growth without harming healthy cells. Transformations of the virus, new viral... (Review)
Review
The goal of an antiviral agent research is to find an antiviral drug that reduces viral growth without harming healthy cells. Transformations of the virus, new viral strain developments, the resistance of viral pathogens, and side effects are the current challenges in terms of discovering antiviral drugs. The time has come and it is now essential to discover a natural antiviral agent that has the potential to destroy viruses without causing resistance or other unintended side effects. The pharmacological potency of thymoquinone (TQ) against different communicable and non-communicable diseases has been proven by various studies, and TQ is considered to be a safe antiviral substitute. Adjunctive immunomodulatory effects in addition to the antiviral potency of TQ makes it a major compound against viral infection through modulating the production of nitric oxide and reactive oxygen species, decreasing the cytokine storm, and inhibiting endothelial dysfunction. Nevertheless, TQ's low oral bioavailability, short half-life, poor water solubility, and conventional formulation are barriers to achieving its optimal pharmacologic benefits. Nano-formulation proposes numerous ways to overcome these obstacles through a small particle size, a big surface area, and a variety of surface modifications. Nano-based pharmaceutical innovations to combat viral infections using TQ are a promising approach to treating surmounting viral infections.
Topics: Antiviral Agents; Benzoquinones; Solubility; Particle Size
PubMed: 37513307
DOI: 10.3390/molecules28145435 -
Viruses Apr 2024This review article describes the current knowledge about the use of antiviral chemotherapeutics in avian species, such as farm poultry and companion birds. Specific... (Review)
Review
This review article describes the current knowledge about the use of antiviral chemotherapeutics in avian species, such as farm poultry and companion birds. Specific therapeutics are described in alphabetical order including classic antiviral drugs, such as acyclovir, abacavir, adefovir, amantadine, didanosine, entecavir, ganciclovir, interferon, lamivudine, penciclovir, famciclovir, oseltamivir, ribavirin, and zidovudine, repurposed drugs, such as ivermectin and nitazoxanide, which were originally used as antiparasitic drugs, and some others substances showing antiviral activity, such as ampligen, azo derivates, docosanol, fluoroarabinosylpyrimidine nucleosides, and novel peptides. Most of them have only been used for research purposes and are not widely used in clinical practice because of a lack of essential pharmacokinetic and safety data. Suggested future research directions are also highlighted.
Topics: Antiviral Agents; Animals; Birds; Virus Diseases; Bird Diseases; Poultry
PubMed: 38675934
DOI: 10.3390/v16040593 -
Medicina (Kaunas, Lithuania) May 2024This review examines hesperidin, a citrus bioflavonoid, as a potential antiviral agent against SARS-CoV-2. The COVID-19 pandemic has demanded an urgent need to search... (Review)
Review
This review examines hesperidin, a citrus bioflavonoid, as a potential antiviral agent against SARS-CoV-2. The COVID-19 pandemic has demanded an urgent need to search for effective antiviral compounds, including those of natural origin, such as hesperidin. The review provides a comprehensive analysis of the chemical properties, bioavailability and antiviral mechanisms of hesperidin, particularly its potential efficacy against SARS-CoV-2. A review of databases, including PubMedPico, Scopus and Web of Science, was conducted using specific keywords and search criteria in accordance with PRISMA (Re-porting Items for Systematic Reviews and Meta-Analysis) guidelines between 2020 and 2024. Of the 207 articles, 37 were selected for the review. A key aspect is the correlation of in vitro, in silico and clinical studies on the antiviral effects of hesperidin with epidemiological data on citrus consumption in China during 2020-2024. The importance of integrating laboratory findings with actual consumption patterns to better understand the role of hesperidin in mitigating COVID-19 was highlighted, and an attempt was made to analyze epidemiological studies to examine the association between citrus juice consumption as a source of hesperidin and the incidence and severity of COVID-19 using China as an example. The review identifies consistencies and discrepancies between experimental and epidemiological data, highlighting the need to correlate the two fields to better understand the potential of hesperidin as an agent against SARS-CoV-2. Challenges and limitations in interpreting the results and future research perspectives in this area are discussed. The aim of this comprehensive review is to bridge the gap between experimental studies and epidemiological evidence and to contribute to the understanding of their correlation.
Topics: Hesperidin; Humans; Citrus; Antiviral Agents; China; COVID-19; Incidence; SARS-CoV-2; COVID-19 Drug Treatment; Severity of Illness Index
PubMed: 38929512
DOI: 10.3390/medicina60060892 -
British Journal of Pharmacology Oct 2023Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. The COVID-19 pandemic began in March 2020 and has... (Review)
Review
Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. The COVID-19 pandemic began in March 2020 and has wrought havoc on health and economic systems worldwide. Efficacious treatment for COVID-19 is lacking: Only preventive measures as well as symptomatic and supportive care are available. Preclinical and clinical studies have indicated that lysosomal cathepsins might contribute to the pathogenesis and disease outcome of COVID-19. Here, we discuss cutting-edge evidence on the pathological roles of cathepsins in SARS-CoV-2 infection, host immune dysregulations, and the possible underlying mechanisms. Cathepsins are attractive drug targets because of their defined substrate-binding pockets, which can be exploited as binding sites for pharmaceutical enzyme inhibitors. Accordingly, the potential modulatory strategies of cathepsin activity are discussed. These insights could shed light on the development of cathepsin-based interventions for COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Cathepsins; Virulence Factors; Pandemics; Antiviral Agents
PubMed: 37403614
DOI: 10.1111/bph.16187 -
Infectious Disorders Drug Targets 2024Monkeypox is a viral disease; its outbreak was recently declared a global emergency by the World Health Organization. For the first time, a monkeypox virus... (Review)
Review
Monkeypox is a viral disease; its outbreak was recently declared a global emergency by the World Health Organization. For the first time, a monkeypox virus (MPXV)-infected patient was found in India. Various researchers back-to-back tried to find the solution to this health emergency just after COVID-19. In this review, we discuss the current outbreak status of India, its transmission, virulence factors, symptoms, treatment, and the preventive guidelines generated by the Indian Health Ministry. We found that monkeypox virus (MPXV) disease is different from smallpox, and the age group between 30-40 years old is more prone to MPXV disease. We also found that, besides homosexuals, gays, bisexuals, and non-vegetarians, it also affects normal straight men and women who have no history of travel. Close contact should be avoided from rats, monkeys and sick people who are affected by monkeypox. To date, there are no monkeypox drugs, but Tecovirimat is more effective than other drugs that are used for other viral diseases like smallpox. Therefore, we need to develop an effective antiviral agent against the virulence factor of MXPV.
Topics: Animals; Female; Humans; Male; Antiviral Agents; Benzamides; Disease Outbreaks; India; Isoindoles; Monkeypox virus; Mpox (monkeypox); Phthalimides; Virulence Factors; Adult
PubMed: 38243966
DOI: 10.2174/0118715265258451231214063506 -
Journal of Medicinal Chemistry Oct 2023Human cytomegalovirus (HCMV) infects individuals of all ages and establishes a lifelong latency. Current antiviral drugs are suboptimal in efficacy and safety and... (Review)
Review
Human cytomegalovirus (HCMV) infects individuals of all ages and establishes a lifelong latency. Current antiviral drugs are suboptimal in efficacy and safety and ineffective against resistant/refractory HCMV. Therefore, there is an unmet clinical need for efficacious, safe, and mechanistically novel HCMV drugs. The recent Food and Drug Administration (FDA) approval of letermovir (LTV) validated the HCMV terminase complex as a new target for antiviral development. LTV targets terminase subunit pUL56 but not the main endonuclease enzymatic function housed in the C terminus of subunit pUL89 (pUL89-C). Structurally and mechanistically, pUL89-C is an RNase H-like viral endonuclease entailing two divalent metal ions at the active site. In recent years, numerous studies have extensively explored pUL89-C inhibition using metal-chelating chemotypes, an approach previously used for inhibiting HIV ribonuclease H (RNase H) and integrase strand transfer (INST). Collectively, the work summarized herein validates the use of metal-binding scaffolds for designing potent and specific pUL89-C inhibitors.
Topics: Humans; Cytomegalovirus; Viral Proteins; Endonucleases; Virus Replication; Ribonuclease H; Antiviral Agents
PubMed: 37827528
DOI: 10.1021/acs.jmedchem.3c01280 -
Nature Communications Oct 2023The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the...
The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the great demand for developing effective therapeutic agents. Here, we report the development of an orally bioavailable SARS-CoV-2 3C-like protease (3CL) inhibitor, namely simnotrelvir, and its preclinical evaluation, which lay the foundation for clinical trials studies as well as the conditional approval of simnotrelvir in combination with ritonavir for the treatment of COVID-19. The structure-based optimization of boceprevir, an approved HCV protease inhibitor, leads to identification of simnotrelvir that covalently inhibits SARS-CoV-2 3CL with an enthalpy-driven thermodynamic binding signature. Multiple enzymatic assays reveal that simnotrelvir is a potent pan-CoV 3CL inhibitor but has high selectivity. It effectively blocks replications of SARS-CoV-2 variants in cell-based assays and exhibits good pharmacokinetic and safety profiles in male and female rats and monkeys, leading to robust oral efficacy in a male mouse model of SARS-CoV-2 Delta infection in which it not only significantly reduces lung viral loads but also eliminates the virus from brains. The discovery of simnotrelvir thereby highlights the utility of structure-based development of marked protease inhibitors for providing a small molecule therapeutic effectively combatting human coronaviruses.
Topics: Mice; Female; Male; Animals; Humans; Rats; SARS-CoV-2; Protease Inhibitors; COVID-19; Antiviral Agents; Enzyme Inhibitors
PubMed: 37833261
DOI: 10.1038/s41467-023-42102-y -
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 -
Molecular Pharmaceutics Aug 2023Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways... (Review)
Review
Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Carcinogenesis; Neoplasms; Antiviral Agents
PubMed: 37486263
DOI: 10.1021/acs.molpharmaceut.2c01080 -
Drug Discovery Today Jan 2024COVID-19 remains a severe public health threat despite the WHO declaring an end to the public health emergency in May 2023. Continual development of SARS-CoV-2 variants... (Review)
Review
COVID-19 remains a severe public health threat despite the WHO declaring an end to the public health emergency in May 2023. Continual development of SARS-CoV-2 variants with resistance to vaccine-induced or natural immunity necessitates constant vigilance as well as new vaccines and therapeutics. Targeted protein degradation (TPD) remains relatively untapped in antiviral drug discovery and holds the promise of attenuating viral resistance development. From a unique structural design perspective, this review covers antiviral degrader merits and challenges by highlighting key coronavirus protein targets and their co-crystal structures, specifically illustrating how TPD strategies can refine existing SARS-CoV-2 3CL protease inhibitors to potentially produce superior protease-degrading agents.
Topics: Humans; SARS-CoV-2; COVID-19; Prospective Studies; Protease Inhibitors; Antiviral Agents
PubMed: 38029836
DOI: 10.1016/j.drudis.2023.103847