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고순영,최원혁 대한의사협회 2014 대한의사협회지 Vol.57 No.1
The goal of antiviral therapy for chronic hepatitis B virus (HBV) infection is to eliminate or suppress HBV with the aim of preventing the devastating complications of cirrhosis, hepatic failure, and hepatocellular carcinoma. Oral antiviral agents suppress but do not eradicate HBV, therefore long-term treatment is necessary to achieve the sustained suppression of viral replication. To optimize the treatment response, treatment should be initiated at an appropriate time with the best available drugs. The indications for treatment are generally based on HBeAg status, serum HBV-DNA level, serum alanine aminotransferase, and the severity of the liver disease. Patients with clinical evidence of active viral replication either with liver inflammation or potentially evolving to cirrhosis should be treated. Nowadays, lamivudine, adefovir, clevudine, telbivudine, entecavir, and tenofovir have been approved for chronic hepatitis B (CHB). Among these, tenofovir and entecavir are potent HBV inhibitors with a high genetic barrier to resistant mutants, so they are recommended by the current treatment guidelines as preferred first-line monotherapies. Failure of antiviral therapy for CHB results in a partial virological response and virological breakthrough, which are related to antiviral-resistant mutants. If genotypic resistance is confirmed, rescue therapy should be initiated, and the regimen should include a potent drug without cross-resistance to prior antiviral agents to minimize the risk of emergence of multiple drug-resistant mutants. This article reviews the current developments in oral antiviral agents, recommendations in CHB treatment guidelines, the medical insurance policy of Korea’s National Health Insurance, and the optimal strategies for using these drugs in clinical practice.
( Won Hyeok Choe ),( So Young Kwon ),( Byung-chul Yoo ),( Jeong Han Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: Oral antiviral agents are main stay of chronic hepatitis B (CHB) treatment and most patients can achieve virological response (VR, undetectable HBV DNA). However, final end point is HBsAg loss and seroconversion. We aimed to evaluate HBsAg level change in CHB patients who achived VR with oral antiviral agents. Methods: This is a retrospective study and the treatment naive CHB patients who achived VR with oral antiviral agents in Konkuk university hospital more than 3 years were enrolled. HBsAg level change was analyzed with Friedman test. Results: Total 105 patients were included in this study. Median age was 51 years and 33 patients were male (31.4%). HBeAg positive patients were 60 (57.1%), cirrhosis patients were 45 (42.9%) and hepatocellular carcinoma patients were 15 (14.3%). Used agents were lamivudine (LMV) in 45 patients (42.9%), entecavir (ETV) in 45 patients (42.9%) and tenofovir (TDF) in 15 patients (14.3%). During 3 years teatment, HBsAg level was reduced from mean 3.24 (log10 IU/mL) to 3.11 (log10 IU/mL) significantly (p=0.005). In subanalysis according to HBeAg status and agents, only ETV treated patients showed significant HBsAg reduction (p=0.001). During 5 years treatment except TDF treated patients due to short duration, HBeAg negative (p<0.001), LMV treated (p=0.001), ETV treated (p=0.038) patients showed significant HBsAg reduction. Conclusions: Successful oral antiviral agents treatment can lead to HBsAg reduction in CHB patients. More powerful agent may reduce HBsAg more rapidly especially in HBeAg negative patients.
Kim, S.M.,Park, J.H.,Lee, K.N.,Kim, S.K.,Ko, Y.J.,Lee, H.S.,Cho, I.S. Elsevier/North-Holland 2012 ANTIVIRAL RESEARCH Vol.96 No.2
Foot-and-mouth disease (FMD) is an economically significant animal disease because of the speed of its transmission. The current FMD vaccine provides no protection until 7days after the vaccination, which reduces its effectiveness in the case of an outbreak. Therefore, to find an alternative method of applying antiviral agents for rapid and enhanced inhibition of the FMD virus (FMDV), we compared the antiviral effects of promising antiviral agents and attempted to apply them in combination. First, we measured and compared the 50% effective concentration (EC<SUB>50</SUB>) to the mean inhibition effects of FMDV, and the 50% cytotoxic concentration (CC<SUB>50</SUB>) to the mean cytotoxicity of antiviral agents such as ribavirin, guanidine-hydrochloride (guanidine-HCl), 6-azauridine, and recombinant adenovirus expressing three small interference RNAs (Ad-siRNA) or porcine interferon-α (Ad-porcine IFN-α) in swine kidney cells (IBRS-2). The selectivity indices of ribavirin (35.2) and 6-azauridine (34.6) were higher than that of guanidine-HCl (26.9). The selectivity indices of Ad-siRNA or Ad-porcine IFN-α were 7x10<SUP>3</SUP> or 7x10<SUP>4</SUP> based on the adenoviral titer. Next, we tested the combined effects of the FMDV inhibition agents. Enhanced inhibition effects were observed in the IBRS-2 cells and in suckling mice from the combination of Ad-porcine IFN-α and Ad-siRNA or ribavirin. The combined application of these recombinant adenoviruses and ribavirin may enhance their inhibitory effect on FMDV and overcome FMDV resistance against antiviral agents.
Plant Metabolites as Antiviral Preparations Against Coronaviruses
Vladimir Berezin,Andrey Bogoyavlenskiy,Madina Alexyuk,Pavel Alexyuk 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.10
In 2019–2020, the Coronavirus (CoV) disease 2019 pandemic created a serious challenge for health care systems in several countries worldwide. A cure has not been developed yet and currently used treatment protocols are aimed at relieving clinical symptoms of the disease. This article presents a retrospective review of biologically active compounds of plant origin that can inhibit the reproduction of CoVs, which makes them potential candidates for creating medicinal antiviral preparations against severe acute respiratory syndrome CoV-2 infections. A literature review of articles from highly rated journals was performed using public databases. The search was carried out using keywords related to CoVs, targets for therapy, and plant as antiviral agents. Although inhibition of viral replication is often considered the common mechanism of antiviral activity exerted by most natural products, several plant-derived compounds show specific activity for particular target viruses. In this context, certain classes of plant preparations can serve as a basis for designing modern antiviral agents. In addition, a large number of plant compounds that are potentially active against CoVs are the main components of certain common dietary supplements that can be used to improve the resistance of a population against certain respiratory infections. In this review, we have attempted to characterize the main groups of biologically active plant compounds that have the potential to disrupt the key stages of CoV replication. It has been shown that the use of certain herbal preparations can change the course of infection.
Management of Side Effects in HCV Patients with Antiviral Agents
Hana Park(박하나) 한국간담췌외과학회 2014 한국간담췌외과학회 학술대회지 Vol.2014 No.4
The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. In addition, first generation protease inhibitors (boceprevir and telaprevir) in combination with PEG-IFN/RBV are a major advancement in the treatment of both naive and treatment-experienced genotype 1 patients. Despite these advances, side effects of treatment in HCV patients with antiviral agents are common. The management of the various side effect profiles is recognized as the challenging problems. This review describes the side effects of current standard therapy of pegylated interferon/ribavirin and new generation DAAs (boceprevir and telaprevir) and proper management of the complications in HCV patients with antiviral agents.
김세연,홍준희 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.10
Racemic syntheses of novel 5′-deoxy-3′,5′,5′-trifluoro-apiose nucleoside phosphonic acid analogs were carried out from 1,3-dihydroxyacetone, to be used as antiviral agents. Nucleophilic displacement of the triflate intermediate with diethyl (lithiodifluoromethyl)phosphonate was performed to yield the corresponding (α,α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor under Vorbrüggen conditions to yield the nucleoside phosphonate analogs. Ammonolysis and hydrolysis of the phosphonates yielded the corresponding nucleoside phosphonic acid analogs. Furthermore, the lipophilic prodrug of the adenine derivative was synthesized to increase cellular uptake. The synthesized nucleoside analogs were screened for their antiviral activity against human immunodeficiency virus (HIV)-1. The bis(SATE) prodrug of the adenine analog exhibited significant in vitro activity against HIV-1.
Hyun Oh, Chang,Hong, Joon Hee WILEY-VCH Verlag 2006 Archiv der Pharmazie Vol.339 No.9
<P>Novel phenyl-branched cyclopropyl nucleosides, phosphonates, and phosphonic acid analogues were designed and synthesized as potential antiviral agents. Coupling of the mesylate 10 with natural bases (U, T, C, A) and desilylation/hydrolysis afforded a series of novel cyclopropyl nucleosides 15–18. Phosphonate and phosphonic acid nucleosides 22–29 were also readily synthesized from the mesylate 21. The synthesized compounds were evaluated for their antiviral activity against various viruses such as HIV-1, HSV-1, HSV-2, and HCMV.</P>
Hong, Joon Hee The Basic Science Institute Chosun University 2015 조선자연과학논문집 Vol.8 No.3
Racemic synthesis of novel 5',5'-difluoro-2'-methyl-apiose nucleoside phosphonic acid analogs was achieved as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate to give the corresponding (${\alpha},{\alpha}$-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the pyrimidine analogs (cytosine, uracil, and thymine) have weak anti-HIV or HCMV activity.
홍준희 조선대학교 기초과학연구원 2015 조선자연과학논문집 Vol.8 No.3
Racemic synthesis of novel 5',5'-difluoro-2'-methyl-apiose nucleoside phosphonic acid analogs was achieved as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate to give the corresponding (α,α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the pyrimidine analogs (cytosine, uracil, and thymine) have weak anti-HIV or HCMV activity.
Synthesis and Antiviral Activity of Novel Methylene Cyclopropyl Nucleosides
kwak, Eun-Yee,Hong, Joon-Hee,Lee, Chong-Kyo,Choi, Bo-Gil The Pharmaceutical Society of Korea 2000 Archives of Pharmacal Research Vol.23 No.6
Novel exomethylene cyclopropyl nucleosides were synthesized as potential antiviral agents. The key intermediate 5 was synthesized in 4 steps, from Feists acid 1 and was condensed with purine derivatives by the $S_N2$ type reaction to give some cyclopropyl nucleosides. The synthesized nucleosides did not showed any significant antiviral activity against HSV-1, HSV-2, HCMV, HIV-1, HIV-2, and HBV up to 100 $\mu\textrm{m}$.