Beclabuvir for the treatment of hepatitis C

Gentile, Ivan; Zappulo, Emanuela; Buonomo, Antonio Riccardo; Maraolo, Alberto Enrico; Borgia, Guglielmo

doi:10.1517/13543784.2015.1059820

Cited by 21 publications

(13 citation statements)

References 70 publications

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“…Previous studies, including phase 3 clinical trials have suggested beclabuvir have a high response rate at post-treatment week [26,27]. Moreover, the pharmacokinetic, efficiency and tolerability were also reported very favorable [28]. Upon intracellular uptake beclabuvir allosterically binds to the non-catalytic Thumb 1 site (Figure 4) of viral RdRp which slowdown the RNA synthesis process [25].…”

Section: Discussionmentioning

confidence: 99%

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Dutta¹,

Shityakov²,

Морозова³

et al. 2020

Preprint

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Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25o C beclabuvir, a non-nucleoside inhibitor of the RdRpHCV can efficiently bind to RdRp SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for binding of beclabuvir to RdRpSARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRpSARS-CoV-2 (ΔGvina = -8.0 kcal mol-1) than that observed with the Thumb 1 domain of RdRpHCV (ΔGvina = -7.1 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549th to 776th amino acid residues of RdRpSARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRpSARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

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Section: Discussionmentioning

confidence: 99%

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Dutta¹,

Shityakov²,

Морозова³

et al. 2020

Preprint

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“…Among them, Beclabuvir is the only antiviral drug with the purpose for the treatment of HCV infection (72,73), whilst the rest are drugs for HIV infection. With a low binding energy of -10.4…”

Section: Drug Perform Well In Our Screening But Not Under Clinical Trialmentioning

confidence: 99%

Systemic in Silico Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server

Xu¹,

Ke²,

Liu³

et al. 2020

Preprint

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<p>The emergence of the new coronavirus (nCoV-19) has brought global impact on human health, whilst the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under current adverse situation, we employ virtual screening tools in searching for drugs and nature products which have been already deposited in the DrugBank in attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Besides, we built an interactive online platform (<a href="https://shennongproject.com:11443/#/home">https://shennongproject.com:11443/#/home</a>) for browsing these results with the visual display of small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory works, it may serve not only as the assessment tool for the new drug discovery but also an educational website to meet general interest from the public.</p>

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“…Beclabuvir is a non-nucleoside NS5B inhibitor and acts by binding allosterically to the NS5B RNA polymerase, ultimately inhibiting the elongation of the nascent viral RNA chain. 110 This process differs from nucleoside NS5B inhibitors that bind directly to the active site of the RNA polymerase. This difference in mechanism between the non-nucleoside and nucleoside NS5B inhibitors is what determines the degree of barrier to resistance.…”

Section: Daclatasvir Beclabuvir and Asunaprevirmentioning

confidence: 99%

“…Additionally, all and have increased exposure with renal insufficiency. 110 , 113 Patients enrolled in trials taking the combination tablet were instructed to take it with food. DCV-TRIO fixed-dose combination was evaluated recently in two phase 3 trials.…”

Section: Daclatasvir Beclabuvir and Asunaprevirmentioning

confidence: 99%

Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection

FakhriRavari

Malakouti

Brady

2016

JCTH

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Hepatitis C virus (HCV) infection affects as many as 185 million people globally, many of whom are chronically infected and progress over time to cirrhosis, decompensated liver disease, hepatocellular carcinoma, and eventually death without a liver transplant. In the United States, HCV genotype 1 constitutes about 75% of all infections. While interferon and ribavirin therapy was the cornerstone of treatment for many years, interferon-free treatments have become the standard of care with the emergence of new direct-acting agents, resulting in more effective treatment, shorter duration of therapy, better tolerability, lower pill burden, and ultimately better adherence. This review will summarize the evidence for the currently available combination therapies as well as emerging therapies in phase 3 trials for treatment of HCV genotype 1.

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Beclabuvir for the treatment of hepatitis C

Cited by 21 publications

References 70 publications

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Systemic in Silico Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server

Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection

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