Application Of Antiviral Drugs Research Articles

Trends and insights in dengue virus research globally: a bibliometric analysis (1995–2023)

BackgroundDengue virus (DENV) is the most widespread arbovirus. The World Health Organization (WHO) declared dengue one of the top 10 global health threats in 2019. However, it has been underrepresented in bibliometric analyses. This study employs bibliometric analysis to identify research hotspots and trends, offering a comprehensive overview of the current research dynamics in this field.ResultsWe present a report spanning from 1995 to 2023 that provides a unique longitudinal analysis of Dengue virus (DENV) research, revealing significant trends and shifts not extensively covered in previous literature. A total of 10,767 DENV-related documents were considered, with a notable increase in publications, peaking at 747 articles in 2021. Plos Neglected Tropical Diseases has become the leading journal in Dengue virus research, publishing 791 articles in this field—the highest number recorded. Our bibliometric analysis provides a comprehensive mapping of DENV research across multiple dimensions, including vector ecology, virology, and emerging therapies. The study delineates a complex network of immune response genes, including IFNA1, DDX58, IFNB1, STAT1, IRF3, and NFKB1, highlighting significant trends and emerging themes, particularly the impacts of climate change and new outbreaks on disease transmission. Our findings detail the progress and current status of key vaccine candidates, including the licensed Dengvaxia, newer vaccines such as Qdenga and TV003, and updated clinical trials. The study underscores significant advancements in antiviral therapies and vector control strategies for dengue, highlighting innovative drug candidates such as AT-752 and JNJ-1802, and the potential of drug repurposing with agents like Ribavirin, Remdesivir, and Lopinavir. Additionally, it discusses biological control methods, including the introduction of Wolbachia-infected mosquitoes and gene-editing technologies.ConclusionThis bibliometric study underscores the critical role of interdisciplinary collaboration in advancing DENV research, identifying key trends and areas needing further exploration, including host-virus dynamics, the development and application of antiviral drugs and vaccines, and the use of artificial intelligence. It advocates for strengthened partnerships across various disciplines to effectively tackle the challenges posed by DENV.

Analyzing and Critically Evaluating the Problems of Antiviral Chemotherapy

Antiviral chemotherapy, an indispensable tool in combating viral infections, faces numerous challenges that often undermine its overall effectiveness and application. This review critically examines the multifaceted issues associated with antiviral chemotherapy, drawing on comprehensive data from NCBI, PubMed, and other reputable academic sources. The primary purpose of this research is to analyze and evaluate key problems such as the development of drug resistance, narrow therapeutic windows, limited spectrum of activity, toxicity, high costs, viral latency, and the complexities inherent in combination therapy. These challenges necessitate a delicate and strategic balance in the development, regulation, and application of antiviral drugs. The research methodology included an exhaustive review of peer-reviewed articles and clinical studies sourced from PubMed and NCBI databases, focusing on ten critical challenges in antiviral chemotherapy. The findings underscore the persistent issue of drug resistance, particularly in RNA viruses like HIV and hepatitis C, which demand ongoing innovation in antiviral drug design and implementation. Additionally, the analysis reveals the significant risks posed by the narrow therapeutic index of many antiviral drugs, which often increases the likelihood of adverse effects, thus limiting their safe and effective use. The study also highlights the formidable challenges posed by viral latency and the limited efficacy of current therapies against emerging and re-emerging viral threats. This research significantly contributes to the understanding of the inherent limitations in existing antiviral therapies and underscores the pressing need for more effective, accessible, and safe treatments. The practical significance lies in offering insights that could guide future research, clinical practice, and policy decisions, ultimately improving global health outcomes in the fight against viral diseases.

Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins.

Early and persistent activation of complement is considered to play a key role in the pathogenesis of COVID-19. Complement activation products orchestrate a proinflammatory environment that might be critical for the induction and maintenance of a severe inflammatory response to SARS-CoV-2 by recruiting cells of the cellular immune system to the sites of infection and shifting their state of activation towards an inflammatory phenotype. It precedes pathophysiological milestone events like the cytokine storm, progressive endothelial injury triggering microangiopathy, and further complement activation, and causes an acute respiratory distress syndrome (ARDS). To date, the application of antiviral drugs and corticosteroids have shown efficacy in the early stages of SARS-CoV-2 infection, but failed to ameliorate disease severity in patients who progressed to severe COVID-19 pathology. This report demonstrates that lectin pathway (LP) recognition molecules of the complement system, such as MBL, FCN-2 and CL-11, bind to SARS-CoV-2 S- and N-proteins, with subsequent activation of LP-mediated C3b and C4b deposition. In addition, our results confirm and underline that the N-protein of SARS-CoV-2 binds directly to the LP- effector enzyme MASP-2 and activates complement. Inhibition of the LP using an inhibitory monoclonal antibody against MASP-2 effectively blocks LP-mediated complement activation. FACS analyses using transfected HEK-293 cells expressing SARS-CoV-2 S protein confirm a robust LP-dependent C3b deposition on the cell surface which is inhibited by the MASP-2 inhibitory antibody. In light of our present results, and the encouraging performance of our clinical candidate MASP-2 inhibitor Narsoplimab in recently published clinical trials, we suggest that the targeting of MASP-2 provides an unsurpassed window of therapeutic efficacy for the treatment of severe COVID-19.

Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development.

Despite the application of antiviral drugs and improved surveillance tools, the number of patients diagnosed with hepatocellular carcinoma (HCC) at an advanced stage and with a dismal prognosis is still on the rise. Systemic treatment with multiple multitargeted tyrosine kinase inhibitors (TKIs), such as sorafenib, has been a widely utilized approach for a decade. In addition, the use of a combination of TKIs with other types of compounds, including immune checkpoint inhibitors (ICIs) and antiangiogenic inhibitors, has shown efficacy in treating advanced HCC. However, the presence of intolerable adverse events, low disease response and control rates, and relative short overall survival of such combinatory therapies makes novel or optimized therapies for advance HCC urgently needed. Locoregional therapy (transarterial chemoembolization, and thermal ablation) can destroy primary tumors and decrease tumor burden and is widely used for HCC management. This type of treatment modality can result in local hypoxia and increased vascular permeability, inducing immunogenic effects by releasing tumor antigens from dying cancer cells and producing damage-associated molecular patterns that facilitate antiangiogenic therapy and antitumor immunity. The combination of systemic and locoregional therapies may further produce synergistic effects without overlapping toxicity that can improve prognoses for advanced HCC. In preliminary studies, several combinations of therapeutic modes exhibited promising levels of safety, feasibility, and antitumor effects in a clinical setting and have, thus, garnered much attention. This review aims to provide a comprehensive, up-to-date overview of the underlying mechanisms of combined systemic and locoregional therapies in the treatment of advanced HCC, commenting on both their current status and future direction.

Current issues of application of anti-viral drugs in hematological patients with hepatitis C virus

Objective. To analyze the effectivity of the use of antiviral drugs Sovaldi 400 mg and Harvoni 90/400 mg in hematological patients.
 Materials and methods. Under our supervision there were 68 patients: 43 (63 %) male and 25 (37 %) female, age from 23 to 80 years, who were treated with antiviral medications intended to hepatitis C virus (HCV). The drugs had prescribed depending on the genotype of the virus; the degree of liver damage; factors that aggravate the course of the disease and the treatment process; responses and adverse reactions that may occur during the process of taking the drug and the timing of use. The 26 patients with genotypes 1 (3), 1c (4), 2 (4), 3a (14) and 1 patient with atypical genotype Sovaldi 400 mg received. Harvoni 90/400 mg was used for treatment HCV 1b genotype in 41 patients and in 1 patient with an atypical genotype. To all patients were investigation according to the algorithm for the diagnosis and treatment of HCV: general clinical (biochemical and hematological) studies and examinations to determine the genotype of the virus, viral load, the degree of liver fibrosis.
 Results and discussion. Given the high infection rate of hematological patients with HCV, which does not allow full treatment, including surgery and chemotherapy, under the program “Treatment of patients with viral hepatitis” antiviral drugs were purchased and treatment was performed in groups of hematological patients. In particular, in patients with the following diagnoses: non-Hodgkin lymphoma (5); myelodysplastic syndromes (1); Hodgkin lymphoma (1); haemophilia A (13) and B (3); leukopenia (3); disaggregation thrombocytopathy (16); immune thrombocytopenic purpura (13); secondary erythrocytosis (5); iron deficiency anemia (5); polycythemia vera (2); chronic lymphocytic leukemia (1). Antiviral therapy was performed according to the clinical protocol for the treatment of viral hepatitis B and C in hematological patients under the supervision of an infectious disease specialist and hematologist. Most patients tolerated treatment satisfactorily and without complications.
 Conclusions. In the last years, direct-acting antiviral drugs become the standard of treatment in hematological patients. For today, HCV should not hinder on the basic of full treatment in the hematological patients as most infected patients may receive antiviral therapy.

The means of combating persistent infection of viral diarrhea

The paper presents results of research into the means of inhibiting persistent infection caused by noncytopathic biotype of bovine viral diarrhea virus. It was shown that bovine viral diarrhea virus, widespread in the cattle population in the whole world, can be a primary cause of pathology development of the respiratory and reproductive organs, and can cause a persistent form of infection in animals. The virus can contaminate fetal serum, cell cultures, trypsin, and other biological products, which leads to a decrease in the quality of biotech products from these materials and the spread of bovine viral diarrhea virus in a population of susceptible animals. The study was done on the model of a continuous calf coronary cell culture persistently infected with the noncytopathic biotype of the bovine viral diarrhea virus. The antiviral effect of two commercial preparations Ribavirin-Lipint and Reaferon-EC-Lipint was studied. The effectiveness of antiviral treatment of the infected cell culture was determined by the reverse transcription polymerase chain reaction, carried out in two versions: with electrophoresis and in real-time mode. It was found that these drugs in doses of 0.05 mg / ml and 30000 IU / ml, respectively, when added to growth medium for 24 consecutive passages, led to a decrease in the infectious activity of the bovine viral diarrhea virus in the cell culture, but did not cure it completely from the persistent infection caused by the noncytopathic biotype of the virus. Application of antiviral drugs is one of the ways to decrease economic losses caused by biological product contamination, the use of persistently infected animals for pedigree purposes and restrictions in international cattle trade.

Prospects for the creation of an antiviral drug based on the raw material of synthetic origin

Aim. To determine the prospects for the creation of a drug based on inosine pranobex using scientific analysis of the characteristics and range of antiviral drugs at the pharmaceutical market ofUkraine.Materials and methods. The material of the article was literary sources of electronic and printed publications on the problems of the use of the substance of synthetic origin – inosine pranobex in modern pharmacotherapy of epidemic mumps, herpes virus human, cytomegalovirus, Epstein-Barr virus, chickenpox virus, influenza virus and parainfluenza. The results were collected and processed using the analytical-comparative, logical and systematic methods of research and the analysis of scientific publications of scientists from different countries of the world, explanation of the reasons and the conceptual position of the authors of the works analyzed on the development and application of antiviral drugs and systematization of the data collected.Results and discussion. The substance of synthetic origin, inosine pranobex, has a direct antiviral effect due to its ability to bind to the ribosomes of infected cells, slows down the synthesis of viral RNA (transcriptional and translational impairment) and leads to inhibition of replication of RNA and DNA-genomic viruses. Induction of interferon formation is also characteristic for the drugs on the basis of this substance. The immunomodulating properties of inosine pranobex are due to the ability of the substance to enhance the differentiation of pre-T-lymphocytes, stimulate mitogen-induced proliferation of T-and B-lymphocytes, increase the functional activity of T-lymphocytes, as well as their ability to form lymphokines. The synthesis of interleukin-1, the expression of membrane receptors and the ability to respond to lymphokines and chemotactic factors are stimulated. Due to the wide range of the pharmacological action, inosine pranobex stimulates mainly cellular immunity, which is especially effective under conditions of cellular immunodeficiency. It has been also found that the use of inosine pranobex helps to reduce the severity of symptoms of herpes infection, duration of the disease; in addition, the substance studied can enhance the antiviral effect of interferon, acyclovir and other antiviral drugs. The above facts prove the relevance of the use of inosine pranobex both for the treatment and prevention of acute and chronic viral infections.Conclusions. The article highlights the current issues of the treatment and prevention of acute respiratory viral infections at the present stage. The classification and features of the mechanism of action of common antiviral drugs are given. A comparison has been made between domestic and international data on the spectrum of application and the pharmacological safety of inosine pranobex. The studies indicate the prospects of creating production of the substance of synthetic origin – inosine pranobex inUkraine. The development of an antiviral drug based on it will significantly reduce the economic costs of industrial production and will be able to guarantee the quality of the medicinal product confirmed by clinical studies.

Analysis of Naturally Occurring Resistance-Associated Variants to NS3/4A Protein Inhibitors, NS5A Protein Inhibitors, and NS5B Polymerase Inhibitors in Patients With Chronic Hepatitis C.

The first NS3/4A hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir were approved in 2011, and both NS5A and NS5B polymerase inhibitors were launched. Recently, direct-acting antivirals (DAAs) have had a major impact on patients infected with HCV. HCV DAAs are highly effective antivirals with fewer side effects. DAAs have been developed for the treatment of HCV infection in combination with PEG-IFN-α/RBV as well as in IFN-free regimens. However, some drug resistance mutations occur when a single oral DAA is used for treatment, which indicates that there is a low-frequency drug resistance mutation in HCV patients before the application of antiviral drugs. Our research showed that natural resistance to HCV DAAs was found in treatment-naive CHC patients and that the drug resistance mutation rates differ in various HCV genotypes. Many challenges posed by natural resistance should be considered in the context of DAA therapies.

Nucleos(t)ide antiviral agents for preventing mother-to-child transmission of hepatitis B virus: an interpretation of relevant international guidelines

A high maternal viral load is the most important factor affecting immunoprophylaxis against mother-infant transmission of HBV. The application of antiviral drugs in pregnant women with a high serum HBV DNA level (>10(6)~10(7) IU/ml) during the second and third trimesters can reduce the prenatal serum HBV DNA level and significantly increase the success rate of blocking mother-infant transmission in neonates. This article interprets the contents related to antiviral therapy for pregnant women carrying HBV with the purpose of blocking mother-infant transmission of HBV in the guidelines published by Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, National Institute for Health and Care Excellence, Korean Association for the Study of the Liver, and World Health Organization.

SOME ASPECTS OF THE MARKETING STUDIES FOR THE PHARMACEUTICAL MARKET OF ANTIVIRAL DRUGS

Antiviral drugs are widely used in medicinal practice. They suppress the originator and stimulate the protection of an organism. The drugs are used for the treatment of flu and ARVI, herpetic infections, virus hepatitis, HIV-infection. Contemporary pharmaceutical market is represented by a wide range of antiviral drugs. Marketing studies are conducted to develop strategies, used for the enhancement of pharmacy organization activity efficiency. Conduction of the marketing researches of pharmaceutical market is the purpose of this study. We have used State Registry of Drugs, State Record of Drugs, List of vital drugs, questionnaires of pharmaceutical workers during our work. Historical, sociological, mathematical methods, and a method of expert evaluation were used in the paper. As the result of the study we have made the following conclusions. We have studied and generalized the literature data about classification and application of antiviral drugs, marketing, competition. The assortment of antiviral drugs on the pharmaceutical market of the Russian Federation was also studied. We have conducted an analysis for the obtainment of the information about antiviral drugs by pharmaceutical workers. We have determined the competitiveness of antiviral drugs, and on the basis of the research conducted we have submitted an offer for pharmaceutical organizations to form the range of antiviral drugs.

Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. Keywords: Emerging therapeutics, infections life cycle, Herpes simplex virus, recent patents, treatment, Viral Entry, ANTI-HSV DRUGS, sacral ganglia, Valomaciclovir, Fusion Peptidic Inhibitors

Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections.

Treatment of herpesvirus infections in HIV-infected individuals.

To discuss strategies available for the treatment of herpesvirus infections in individuals infected with HIV. Information was obtained from controlled and uncontrolled clinical trials, abstracts, conference proceedings, and review articles. Emphasis was placed on controlled investigations in subjects infected with HIV. Data from human studies were extracted by the author and evaluated according to the patient population studied, sample size, dosage regimen, and therapeutic response. Herpes group viruses are common opportunistic pathogens in HIV-infected individuals. Zoster, caused by varicella-zoster virus (VZV), is an early indication of the loss of cell-mediated immunity and HIV disease progression. Anorectal mucocutaneous disease is the most common manifestation caused by herpes simplex virus (HSV). Acyclovir is the drug of choice for treatment of both VZV and HSV infections. Cytomegalovirus (CMV) is the most common life-threatening viral infection in patients with AIDS; retinitis is the most frequent clinical manifestation. The response rate of CMV retinitis to initial treatment with either ganciclovir or foscarnet is equivalent, approximately 60-90 percent. Recent data suggest that the survival benefit may be greater with foscarnet. Advances in the development and application of antiviral drugs for herpes group viruses have made treatment and, in some cases, prevention of infections possible. Future efforts, aimed at earlier intervention and suppression of latent virus, may offer additional improvement in quality of life for the HIV-infected individual.