anti-HCV Drugs Research Articles

Real-World Efficacy and Safety of Pangenotypic Direct-Acting Antivirals Against Hepatitis C Virus Infection.

Advances in the development of Direct-Acting Antivirals (DAAs), particularly pangenotypic drugs, have led to a high rate of hepatitis C virus (HCV) eradication. Notably, real- world studies have confirmed the efficacy and safety of pangenotypic DAA combinations reported in registration trials. The aim of this study was to review the treatment recommendations, and the efficacy and safety data of anti-HCV pangenotypic drugs reported in registration clinical trials and in recent real-life cohort studies. We reviewed the efficacy and safety data of pangenotypic anti-HCV drug combinations reported in original articles and in online conference abstracts. Current pangenotypic drug combinations resulted in very high rates of sustained virologic response and few adverse reactions in real-life settings. SVR12 rates in real-life studies ranged from 90-100% depending on the pangenotypic combination, the HCV genotype and the stage of liver disease. Most adverse reactions reported in real-life settings were mild in intensity and rarely led to treatment discontinuation. These results are in accordance with those of clinical trials. Pangenotypic DAAs result in very high rates of sustained virologic responses and are well tolerated. However, they are contraindicated in patients with decompensated cirrhosis or advanced chronic kidney disease who failed previous DDA-based treatment. Further research is required to customize treatment to "unpackage" current DAA combinations and to develop generic drugs against HCV.

Effects of resistance-associated variants in genotype 2hepatitis C virus on viral replication and susceptibility to antihepatitis C virus drugs.

Development of direct-acting antivirals (DAAs) has made antihepatitis C virus (HCV) treatment highly safe and effective. However, the emergence of resistant-associated variants (RAVs) after failure of DAA therapy affects retreatment outcomes. In particular, genotype 1 HCV with P32 deletion has been reported to be highly resistant to all approved non-structural protein (NS)5A inhibitors. However, analysis of RAVs in genotype 2 HCV has been limited. Accordingly, in this study, we evaluated the roles of genotype 2 HCV variants in antiviral drug efficacy. We utilized HCV-2b/2a (JFH-1) chimeric virus (genotype 2a), which replicates more robustly than JFH-1. We constructed various genotype 2a JFH-1-based HCV cell culture systems with NS3 (D168E), NS5A (F28S, F28S/M31I, P32 deletion, and Y93H), and NS5B (S282T) RAVs and analyzed the replication ability and sensitivity to various anti-HCV reagents. Genotype 2a-based HCV with NS5A-P32 deletion could not replicate even in long-term cultures. Genotype 2a-based HCV with NS5A-F28S/M31I showed significantly higher replication ability than the wild-type strain, and replication could not be suppressed, even with high concentrations of NS5A inhibitors, including pibrentasvir and velpatasvir (<1000-10 000 fold-resistance compared with the wild-type strain). However, genotype 2a-based HCV with NA5A-F28S/M31I was sensitive to HCV protease inhibitor, NS5B inhibitor, interferon-α, and ribavirin. Genotype 2a-based HCV with NS5B-S282T was resistant to sofosbuvir, but was highly sensitive to ribavirin compared with the control. When undertaking retreatment for genotype 2a HCV-infected patients who fail to respond to DAAs, the optimized retreatment should be chosen according to the sensitivity of the emerging RAVs to anti-HCV drugs.

Validated RP-HPLC Method for Simultaneous Determination of Ribavirin, Sofosbuvir and Daclatasvir in Human Plasma: A Treatment Protocol Administered to HCV Patients in Egypt

Egypt has the highest prevalence of hepatitis C virus (HCV) in the world thus it launched a national program for eliminating HCV aiming to treat 300,000 HCV patients per year. Three anti-HCV co-administered drugs; ribavirin (RBV), sofosbuvir (SF) daclatasvir (DAC) were simultaneously determined in human plasma by a validated, simple and sensitive RP-HPLC method using propyl paraben as an internal standard. Liquid-liquid extraction using ethyl acetate was used for samples extraction. Chromatographic separation was achieved on Scharlau® C18 column (250 × 4.6 mm2, 5 μm). Gradient elution was employed with a mobile phase mixture of water and acetonitrile at a flow rate 1 mL/min. UV detection using photodiode array detector was carried out at 207, 260 and 312 nm for RBV, SF and DAC, respectively. Method validation was performed according to the FDA guidelines for bioanalytical method validation. The calibration curves were linear over the ranges (0.5-80, 0.1-40 and 0.5-80 μg/mL) with average recoveries (100.64-108.28%, 98.48-105.91% and 97.68-101.38%) for RBV, SF and DAC, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Stability assays revealed that the three studied analytes were stable during sample storage, preparation and injection. The method can be successfully applied in routine analysis of plasma of HCV patients treated with this combination therapy which aids in therapeutic drug monitoring and patients' follow-up especially in Egypt and other developing countries fighting HCV.

Employ fourier transform infrared spectroscopy spectroscopy for determination of second-generation anti-HCV (sofosbuvir, daclatasvir) drugs: Application to uniformity of dosage units

Recently approved anti-HCV drugs are a breakthrough new medication for the treatment of all genotypes hepatitis C virus infection. A selective, non-destructive and precise fourier transform infrared (FTIR) spectroscopic method was established and validated for the direct determination of daclatasvir dihydrochloride (DAC) and sofosbuvir (SOF) in pharmaceutical dosage forms. The method based on measurement the stretching bands of carbonyl group spectral range from 1695 to 1740 cm−1 for the studied drugs. The suggested procedures were completely validated through ICH guidelines with linear ranges of 0.25 −20.0 and 0.5 −20.0 mg g−1 for DAC and SOF, respectively. The values of LOQ were 0.149 and 0.172 and the values of LOD were 0.049 and 0.057 mg g−1 for DAC and SOF, respectively. Also, the analytical procedure was developed in agreement with green chemistry and the obtained results are found to be in a good agreement with that of the destructive methods. Moreover, the method was successfully applied for the direct and rapid supervision the uniformity of dosage units for the studied anti-HCV drugs in their pharmaceutical tablets dosage form.

Low susceptibility of asunaprevir towards R155K and D168A point mutations in HCV NS3/4A protease: A molecular dynamics simulation

Hepatitis C has become an important health problem that requires expensive treatment and leads to liver tumorigenesis. Hepatitis C virus (HCV), which is the main cause of hepatitis C, has a high mutation rate due to the lack of proofreading activity of the RNA polymerase enzyme. The NS3/4A serine protease is an important target for anti-HCV drug discovery and development because of its crucial role in the cleavage of the polypeptides involved in viral replication. In the present study, all-atom molecular dynamics simulation was performed to elucidate the effect of the single point mutations R155K and D168A in the HCV genotype 1 NS3/4A protease on the structural dynamics, molecular interactions and susceptibility of asunaprevir (ASV), a second-generation NS3/4A protease inhibitor. Principal component analysis indicated that these two mutations converted the direction of motion of residues 123, 155 and 168 in the binding pocket to significantly point outwards from ASV, resulting in a loss of the hydrogen bond network of residues R123···R155···D168. The free energy calculations based on different semiempirical QM/MM-GBSA methods revealed that the binding affinity of ASV with the two mutant forms of the NS3/4A protease was significantly decreased in the order of wild-type < R155K < D168A. This work provided useful structural information regarding the atomistic understanding of acquired drug resistance against ASV caused by the R155K and D168A mutations.

Comparison of Anti-HCV Activity of Multiple Punica granatum Extracts and Fractions in Virus-infected Human Hepatocytes.

Plants extracts and their bioactive constituents can provide an alternative approach for new treatment. Pakistani flora reveals a huge, largely untapped source of potential antiviral constituents. High-cost concerns of direct-acting anti-HCV drugs limit their employment specifically in developing countries like Pakistan. Therefore, discovery of inexpensive and nontoxic agents is needed for HCV treatment. In this study, we used plasmid constructs of pCR3.1/FLAGtag/HCV NS3/4A (genotype 1a & 3a) and Punica granatum extracts (PK AV 003) and semi-purified fractions (P1-P11) were evaluated for their anti-HCV activity. Acetone extract along with two fractions (P4 & P11) revealed a useful therapeutic index. The fractions P4 (IC50=28.5±0.02 µg/ml; IC25=16±0.02 µg/ml) and P11 (IC50=72±0.02 µg/ml; IC25=41±0.03 μg/ml) dramatically suppressed HCV replication as measured by quantitative PCR (qPCR) and HCV NS3 protein expression level in transient transfection model. Consistent with suppression in genome replication, inhibition of HCV infectious particles by PK AV 003 extract was also judged in an infectious model system. This data is the first description of Pakistani indigenous cultivated fruit-producing plant, Punica granatum, possessing anti-HCV activity. Further analyses are being performed for investigating the mechanistic studies and structural characterization of purified fractions of PK AV 003. Our findings suggest that PK AV 003 fruit extract might be useful as an add-on therapeutic candidate for treating HCV infection.

Synthesis, biological evaluation and mode of action studies of novel amidinourea inhibitors of hepatitis C virus (HCV)

Novel amidinourea derivatives have been synthesised and evaluated for their antiviral activity against Hepatitis C Virus (HCV). A compound with an amidinourea-spermine chemical structure, different from that of standard anti-HCV drugs, showed micromolar activity against HCV and excellent viability. Studies on the mode of action revealed that the new compound may act against HCV through the inhibition of IRES-mediated translation.

Anti-hepatitis C Virus Strategy Targeting the Entry Steps

Hepatitis C virus (HCV) infection is a major leading cause of chronic severe liver diseases such as cirrhosis and hepatocellular carcinoma. The recent direct-acting antivirals (DAAs) for the treatment of HCV infection offer very high cure rates, but DAAs are vulnerable to drug resistance because HCV is an RNA virus, which generally has very high mutation rates. DAA resistance-associated variants of HCV could reduce the effectiveness of DAAs in the future. Thus, the continuous development of new anti-HCV drugs against different target molecules is needed. We have been studying the host factors involved in HCV entry into cells. From those studies, we obtained novel candidates for host-targeting anti-HCV entry inhibitors, such as monoclonal antibodies against HCV receptors, which can be used together with DAAs. In this symposium review, we present and discuss our recent work on anti-HCV strategies targeting HCV entry steps.

Novel spectrofluorimetric approach for determination of ledipasvir through UV-irradiation: application to biological fluids, pharmacokinetic study and content uniformity test.

A highly sensitive and specific fluorescence dependent approach was created for quantitation of a recently approved anti-HCV drug (ledipasvir). This approach relies on the innovative enhancement in fluorescence intensity of ledipasvir upon exposing the cited drug to direct UV irradiation as a photo-physical fluorescence enhancer. The fluorescence of the resultant solution was measured at an emission peak of 375 nm (321 nm excitation). The photoluminescence properties of the resultant product were carefully examined and the quantitative rectilinear concentration plot for the method was 5.0–150.0 ng mL−1 with a detection limit of 0.9 ng mL−1 and a quantitation limit of 2.7 ng mL−1. The excellent analytical features of the proposed method allow to the specific and sensitive estimation of ledipasvir either in plasma samples or in tablet dosage form without any interference from pharmaceutical excipients or other co-formulated anti-HCV drugs (sofosbuvir). The developed analytical and bio-analytical procedures were created and validated according to ICH guidelines and FDA guidelines, respectively. Since the main elimination route for ledipasvir is via faecal excretion, the studied drug was determined for the first time in faecal samples by the method with adequate recovery. Moreover, the pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0–t, and AUC0–∞) for ledipasvir were determined by the proposed method. Additionally, the proposed method was successfully applied for supervising the content uniformity for ledipasvir in its pharmaceutical tablets.

Design, Synthesis, Molecular Modeling Studies and Biological Evaluation of N'-Arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide Derivatives as Novel Anti-HCV Agents.

HCV-induced hepatitis is one of the most debilitating diseases. The limited number of anti-HCV drugs and drug-resistance necessitate developing of new scaffolds with different mode of actions. HCV non-structural protein 5B (NS5B) is an attractive target for development of novel inhibitors of HCV replication. In this paper, new N′-arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives were designed based on the pharmacophores of HCV NS5B active site binding inhibitors. Designed compounds were synthesized and evaluated for their inhibitory activities in a cell-based HCV replicon system assay. Among tested compounds, compounds 18 and 20 were found to be the most active (EC50 = 35 and 70 µM, respectively) with good selectivity index (SI > 2) in the corresponding series. Molecular modeling studies showed that the designed compounds are capable of forming key coordination with the two magnesium ions as well as interactions with other key residues at the active site of HCV NS5B.

Molecularly imprinted polymer/reduced graphene oxide‒based carbon‒paste sensor for highly sensitive determination of the anti‒HCV drug daclatasvir dihydrochloride

The recent discovery of the novel viral RNA‒dependent RNA polymerases for treatment of HCV opened the doors for the development of a large number of anti−HCV drugs which require a concurrent development of sensitive analytical methods for their quality‒control and analysis. In this work, we report the first molecularly imprinted polymer‒based electrochemical sensor for the determination of the anti−HCV drug, daclatasvir dihydrochloride (DCT). Since liver patients require continuous medical follow up during the period of their treatment, it is very necessary to develop a simple and fast method for monitoring the DCT concentration in the patient’s biological fluids. In addition, quality control laboratories are in an urgent need for various rapid analytical methods for such a novel drug. The sensor is based on the modification of the traditional carbon‒paste sensor with molecularly imprinted methacrylic acid, cross linked with ethylene glycol dimethacrylate, as a selective adsorbent for DCT, and reduced graphene oxide (RGO) as a sensitizer. The Hartree‒Fock method of calculation was used to optimize the template/functional monomer ratios so as to avoid trial‒and‒error experimental synthesis procedures and to give information about the binding of the template to the functional monomer. The sensor was fully characterized with the aid of cyclic voltammetry, FTIR analysis and scanning electron microscopy (SEM). After optimization of the analytical parameters, the sensor was found to work efficiently at pH 2.5 (Britton Robinson buffer) and a scan rate of 500 mV/s. The sensor showed a good linearity over the concentration range of 40.6 pg/mL to 812 μg/mL with a correlation coefficient of 0.9881. The detection and quantification limits were found to be 12.2 and 40.2 pg/mL, respectively. The proposed sensor was applied for the determination of DCT in bulk solution, pharmaceutical formulation and human urine and plasma samples and excellent recovery values ranging from 99.48 to 103.70% were obtained indicating the accuracy of the proposed sensor.

Stability of β-turn in LaR2C-N7 peptide for its translation-inhibitory activity against hepatitis C viral infection: A molecular dynamics study.

Hepatitis C virus (HCV) requires an essential host factor, human La protein, for its translation and replication activity. Earlier, it was demonstrated that a 24-mer synthetic peptide (LaR2C) encompassing residues 112 to 184 of the natural human La protein interacts with the HCV internal ribosome entry site (IRES) and inhibits translation. Interestingly, a shorter version of the same LaR2C peptide, LaR2C-N7, containing residues 174 to 180 (KYKETDL), with a unique β-turn secondary structure, is sufficient to inhibit IRES mediated translation of HCV. Hence, it is imperative to understand the role of each amino acid of this heptapeptide towards β-turn formation which will then help in designing potential drugs against HCV infection. Here, we use Nanoscale Molecular Dynamics (NAMD) simulation to investigate the factors modulating its β-turn formation and stability. Using 100 ns simulation paradigms, we find that the peptide populated the type 1 β-turn conformation in its free form in solution. However, simulation of the single-site mutants of the heptapeptide revealed that none of the 7 mutants retained the β-turn conformation with sufficient stability. We observed that the β-turn was stabilized mainly by the side chain interaction, salt-bridge and weak hydrogen bonds between K3 and D6 residues. Y2, K1 and K3 sites upon mutation heavily destabilized the β-turn when compared to alteration at the E4 and T5 sites which would then drastically reduce its HCV RNA IRES binding capabilities. Taken together, our results provide a basis for designing peptidomimetics as potential anti-HCV drug candidates.

Hepatitis C virus infection and chronic renal disease: A review.

Hepatitis C virus (HCV) isa parenterally-transmitted hepatotropic virus that often causes chronic infection, which can progress to cirrhosis and hepatocellular carcinoma. Development of highly effective direct-acting anti-viral agents (DAAs) has led to a paradigm change in the treatment of HCV infection over the last 4-5years. Patients with chronic kidney disease (CKD) are at a higher risk of acquiring HCV infection. In these patients, diagnosis of HCV infection, assessment of the consequent liver disease and management of HCV infection pose some specific problems. This article reviews the available recent information on HCV infection and CKD, including the association between these conditions and their effect on each other, and prevention, evaluation, and management of HCV infection in persons with CKD. This review looks at this issue particularly from the perspective of readers in Asia, especially India, since the epidemiology of HCV-CKD association and the repertoire of anti-HCV drugs available in this region differ from those elsewhere.

Characterization of In vitro Inhibitory Effects of Consensus Short Interference RNAs against Non-Structural 5B Gene of Hepatitis C Virus 1a Genotype

Purpose: Chronic hepatitis C has infected approximately 170 million people worldwide. The novel direct-acting antivirals have proven their clinical efficacy to treat hepatitis C infection but still very expensive and beyond the financial range of most infected patients in low income and even resource replete nations. This study was conducted to establish an in vitro stable human hepatoma 7 (Huh-7) cell culture system with consistent expression of the non-structural 5B (NS5B) protein of hepatitis C virus (HCV) 1a genotype and to explore inhibitory effects of sequence-specific short interference RNA (siRNA) targeting NS5B in stable cell clones, and against viral replication in serum-inoculated Huh-7 cells. Materials and Methods:In vitro stable Huh-7 cells with persistent expression of NS5B protein was produced under gentamycin (G418) selection. siRNAs inhibitory effects were determined by analysing NS5B expression at mRNA and protein level through reverse transcription-polymerase chain reaction (PCR), quantitative real-time PCR, and Western blot, respectively. Statistical significance of data (NS5B gene suppression) was performed using SPSS software (version 16.0, SPSS Inc.). Results: siRNAs directed against NS5B gene significantly decreased NS5B expression at mRNA and protein levels in stable Huh-7 cells, and a vivid decrease in viral replication was also exhibited in serum-infected Huh-7 cells. Conclusions: Stable Huh-7 cells persistently expressing NS5B protein should be helpful for molecular pathogenesis of HCV infection and development of anti-HCV drug screening assays. The siRNA was effective against NS5B and could be considered as an adjuvant therapy along with other promising anti-HCV regimens.

Study the Biochemical Activities of Anti-HCV Drugs on Thioacetamide Induced Hepatic Fibrosis

Study the Biochemical Activities of Anti-HCV Drugs on Thioacetamide Induced Hepatic Fibrosis

RNA triphosphatase DUSP11 enables exonuclease XRN-mediated restriction of hepatitis C virus

Seventy percent of people infected with hepatitis C virus (HCV) will suffer chronic infection, putting them at risk for liver disease, including hepatocellular carcinoma. The full range of mechanisms that render some people more susceptible to chronic infection and liver disease is still being elucidated. XRN exonucleases can restrict HCV replication and may help to resolve HCV infections. However, it is unknown how 5' triphosphorylated HCV transcripts, primary products of the viral polymerase, become susceptible to attack by 5' monophosphate-specific XRNs. Here, we show that the 5' RNA triphosphatase DUSP11 acts on HCV transcripts, rendering them susceptible to XRN-mediated attack. Cells lacking DUSP11 show substantially enhanced HCV replication, and this effect is diminished when XRN expression is reduced. MicroRNA-122 (miR-122), a target of current phase II anti-HCV drugs, is known to protect HCV transcripts against XRNs. We show that HCV replication is less dependent on miR-122 in cells lacking DUSP11. Combined, these results implicate DUSP11 as an important component of XRN-mediated restriction of HCV.

Structural Flexibility in HCV NS5B Polymerase and Molecular Modelling of Anti-HCV Drugs

Structural Flexibility in HCV NS5B Polymerase and Molecular Modelling of Anti-HCV Drugs

Discovery and characterization of a novel HCV inhibitor targeting the late stage of HCV life cycle.

Currently approved anti-HCV drugs, the direct-acting antivirals (DAAs), are highly effective and target the viral RNA replication stage of the HCV life cycle. Due to high mutation rate of HCV, drug resistant variants can arise during DAA monotherapy. Thus, a combination of DAAs is necessary to achieve a high response rate. Novel HCV inhibitors targeting the HCV late stage such as assembly and release may further improve combination therapy with the DAAs. Here we characterize one late stage-targeting candidate compound, 6-(4-chloro-3-methylphenoxy)-pyridin-3-amine (MLS000833705). We treated HCV-infected cells with MLS000833705 and other HCV inhibitors and examined HCV RNA and infectious titres. We evaluated the colocalization of HCV core and lipid droplets by confocal microscopy. We performed HCV core-proteinase K digestion assay and several lipid assays to study the mechanism of MLS000833705. We showed that MLS000833705 decreased extracellular HCV RNA levels more than intracellular HCV RNA levels in HCV infectious cell culture. Similarly, MLS000833705 reduced infectious HCV titres substantially more in the culture supernatant than intracellularly. Confocal microscopy showed that MLS000833705 did not affect the colocalization of HCV core protein with cellular lipid droplets where HCV assembles. HCV core-proteinase K digestion assay showed that MLS000833705 inhibited the envelopment of HCV capsid. Our study demonstrates that MLS000833705 is a late-stage HCV inhibitor targeting HCV morphogenesis and maturation. Therefore, MLS000833705 can be used as a molecular probe to study HCV maturation and secretion and possibly guide development of a new class of HCV antivirals.

Successful Treatment of HCV/TB co-infected Patient With Sofosbuvir and Daclatasvir: A Case Report

Aim: This case report suggests proper management of patients co-infected with both HCV and TB. Patients &amp; methods: A 77-year-old female patient visited a primary care physician for a routine follow-up because she had past history of HCV in 2011, but she was successfully treated with interferon-therapy. She experienced HCV relapse in 2016 but did not respond to sofosbuvir and ribavirin and it was later on confirmed that she had TB which made the treatment of HCV more challenging. Results: This is the first evidence that highlights sofosbuvir, daclatasvir and ribavirin as an optimal treatment regimen for patients co-infected with TB. Furthermore, it is necessary to treat TB before initiating HCV treatment because of risk of hepatotoxicity. Conclusion: Co-infection of TB in HCV patients alters treatment response toward nucleotide analog inhibitor, sofosbuvir, an approved anti-HCV drug with high rate of sustained virological response.

Calculation of Wiener Indices of Thiazolides: The Potent Inhibitors of Hepatitis B Virus and Hepatitis C Virus Replication

Background: Hepatitis C Virus is the leading cause of death in liver-related diseases globally. The identification of innovative drug targets and inexpensive therapeutic agents remain a high priority for chronic HCV infection management. In the last few decades, the availability of highly effective interferon-free regimens for HCV treatment is the only possible option for cure of the large number of chronic HCV patients. Direct acting antiviral drugs, such as Sovaldi, are expensive and their efficacy varies from genotype to genotype. In addition, these drugs are advised in combination with ribavirin and interferon, which makes the treatment costly. Thiazolide derivatives are recently emerging antiviral agents that may change current and future therapies for liver complications caused by HBV and HCV. Nitazoxanides are synthetic nitrothiazolyl-salicylamide derivative of thiazolide, which have been used as anti-HCV drugs. The derivatives of thiazolides were randomly screened for anti-HCV and anti-HBV activity in a biological system, yet the stability and other properties of these compounds were not tested. Representing chemical compounds with Hosoya-polynomial produces closed forms of many topological indices, which correlate with the chemical properties of the material under investigation. These indices are used in the development of quantitative structure-activity relationships (QSARs), in which the biological activity and other properties of molecules like boiling point, stability, strain energy, radius of gyration, and viscosity are correlated with their structures.In this paper, Hosoya-polynomials and Weiner indices of some derivatives of thiazolides were determined. Graphs of Hosoya polynomial for these derivatives were also plotted. Objectives: In this study, therefore, it was attempted to extend the research to check the stability and other properties of thiazolide derivatives using the Hosoya-polynomial and Wiener index. Methods: In the first step, Hosoya polynomials of some famous classes of thiazolides were computed, followed by computation of F Wiener indices of thiazolide derivatives. Distance-based graph invariants were used as a structure-descriptor for predicting various physicochemical properties of organic compounds. The Weiner index of 8 derivatives of thiazolidines was computed, including RM-4832, RM-4848, RM-4850, RM-4851, RM-4852, RM-4850, Tizoxanide, and Nitazoxanide. Results: These indices indicate the physiochemical properties of these compounds in relation to stability in the given biological environment. The Wiener indices of the studied compounds ranged from 374 to 684. Out of 8 analyzed compounds, 3 showed Wiener indices of 374. RM-4863 had a maximum index value of 684. Graphs were also drawn for Hosoya polynomials of all these thiazole derivatives. Conclusions: The results confirmed that RM-4863 is a stable physiochemical compound, which might be used as an effective drug for treating viral infections, including HCV and HBV.