SOFOSBUVIR

DrugBank ID: db08934
DrugCentral: sofosbuvir
Synonymous :s)-isopropyl 2-((s)-(((2r,3r,4r,5r)-5-(2,4-dioxo-3,4- dihydropyrimidin-1(2h)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)- (phenoxy)phosphorylamino)propanoate | sofosbuvir


Drug Sentece Context


Table 1. Analysis of context sentence of sofosbuvir gene in 33 abstracts.

pmid sentence
32119961 Additionally, the newly emerged Wuhan HCoV RdRp model is targeted by anti-polymerase drugs, including the approved drugs Sofosbuvir and Ribavirin. […] The results suggest the effectiveness of Sofosbuvir, IDX-184, Ribavirin, and Remidisvir as potent drugs against the newly emerged HCoV disease.
32194944 The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.
32222463 The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp.
32284326 In this regard, the triphosphate forms of 2’-C-methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits.
32338164 The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.
32387040 Sofosbuvir, the clinically approved anti-hepatitis C virus (HCV) drug, is also capable of suppressing other families of positive-strand RNA viruses; Flaviviridae and Togaviridae. […] Coronaviruses are a family of positive-strand RNA viruses with conserved polymerase, so SARS-CoV-2 RdRp is very likely to be effectively inhibited by sofosbuvir. […] More importantly, sofosbuvir is safe and well tolerated at 400 mg daily in a 24 week therapeutic regimen. […] Sofosbuvir active metabolite, however, shows an extremely high intracellular stability So, it is hypothesized that SARS-CoV-2 infection could also be susceptible to sofosbuvir and we were convinced to design and run a clinical trial to evaluate the effect of sofosbuvir 400 mg (in combination with velpatasvir 100 mg, as add-on treatment, in addition to standard of care) on the COVID-19.
32405423 Minimum estimated costs of production were US $0.93/day for remdesivir, $1.45/day for favipiravir, $0.08/day for hydroxychloroquine, $0.02/day for chloroquine, $0.10/day for azithromycin, $0.28/day for lopinavir/ritonavir, $0.39/day for sofosbuvir/daclatasvir and $1.09/day for pirfenidone.
32419838 A knowledge-based analysis strongly suggests a possible repositioning of the anti-HCV direct antiviral agent (DAA) Sofosbuvir as treatment for SARS-CoV-2. […] Indeed, the RNA-dependent RNA-polymerases (RdRp) of the two viruses show high sequence and structural homology, supporting the likelihood of binding the Sofosbuvir molecule with similar efficiency.
32420958 Sofosbuvir may be a potential option in the treatment of COVID-19 based on the similarity between the replication mechanisms of the HCV and the coronavirus. […] According the limited experimental evidences, it is hypothesized that sofosbuvir might be a potential option to improve care of patients with COVID-19 especially at the start of the disease and before invasion of the virus into the lung parenchymal cells. […] Efficacy and safety of sofosbuvir in treatment of COVID-19 may be considered in future clinical studies.
32518317 The structural superposition of the hepatitis C virus polymerase bound to sofosbuvir, a nucleoside analog antiviral approved for hepatitis C virus infections, with the SARS-CoV polymerase shows that the residues that bind to the drug are present in the latter. […] Moreover, a multiple alignment of several SARS-CoV-2, SARS and MERS-related coronaviruses polymerases shows that these residues are conserved in all these viruses, opening the possibility to use sofosbuvir against these highly infectious pathogens.
32562705 We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine.
32692185 On the basis of our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues (the triphosphates of Sofosbuvir, Alovudine, and AZT) inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). […] Here, we used polymerase extension experiments to demonstrate that the active triphosphate form of Sofosbuvir (an FDA-approved hepatitis C drug) is incorporated by SARS-CoV-2 RdRp and blocks further incorporation.
32787752 Furthermore, ribavirin may also be a potential treatment against CHIKV; sofosbuvir against ZIKV; celgosivir against DENV, and favipiravir against EBOV and MARV, representing new hopes against these pathogens.
32812025 We assessed the efficacy of sofosbuvir and daclatasvir with ribavirin for treating patients with COVID-19. […] Patients were randomly assigned to 400 mg sofosbuvir, 60 mg daclatasvir and 1200 mg ribavirin (intervention group) or to standard care (control group). […] The number of ICU admissions in the sofosbuvir/daclatasvir/ribavirin group was not significantly lower than the control group (0 versus 4, P = 0.109). […] The cumulative incidence of recovery was higher in the sofosbuvir/daclatasvir/ribavirin arm (Gray’s P = 0.033). […] There were trends in favour of the sofosbuvir/daclatasvir/ribavirin arm for recovery and lower death rates.
32812039 The aim of this trial was to assess if the addition of sofosbuvir and daclatasvir improved clinical outcomes in patients with moderate or severe COVID-19. […] Patients were randomized into a treatment arm receiving sofosbuvir and daclatasvir plus standard care, or a control arm receiving standard care alone. […] The addition of sofosbuvir and daclatasvir to standard care significantly reduced the duration of hospital stay compared with standard care alone.
32812051 Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. […] This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. […] Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. […] Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. […] The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. […] The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. […] The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04-0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1-12.1, P < 0.01).
32965013 There are several potential medications available for COVID-19, such as Interferon α (IFN-α), Teicoplanin, Ribavirin, Galidesivir, Lopinavir/Ritonavir, Chloroquine phosphate, Arbidol, Velpatasvir, Favipiravir, Ledipasvir, Remdesivir, Sofosbuvir, Darunavir, Qingfei Paidu Decoction (QPD), and Imatinib.
32967116 The drugs studied include chloroquine, ivermectin, remdesivir, sofosbuvir, boceprevir, and α-difluoromethylornithine (DMFO).
33024223 After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2. […] We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fidelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fidelity DNA polymerase. […] Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells; additionally, COVID-19 clinical trials with EPCLUSA and with Sofosbuvir plus Daclatasvir have been initiated in several countries. […] We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic. […] These results offer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials.
33060595 In contrast, most of the clinically approved antivirals, including tenofovir alafenamide, emtricitabine, sofosbuvir, ledipasvir, and velpatasvir were inactive at concentrations up to 10 µM.
33063117 The combination of sofosbuvir and daclatasvir has a well-established safety profile and improves clinical outcomes in HCV patients. […] In silico and in vitro studies suggest that sofosbuvir/daclatasvir may show antiviral activity against SARS-CoV-2. […] Three clinical trials comparing sofosbuvir/daclatasvir-based regimens with a comparator in hospitalized COVID-19 patients were combined in a meta-analysis. […] Clinical recovery within 14 days of randomization was higher in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 1.34 (95% CI = 1.05-1.71), P = 0.020]. […] Sofosbuvir/daclatasvir improves time to clinical recovery [HR = 2.04 (95% CI = 1.25-3.32), P = 0.004]. […] The pooled risk of all-cause mortality was significantly lower in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 0.31 (95% CI = 0.12-0.78), P = 0.013]. […] Available evidence suggests that sofosbuvir/daclatasvir improves survival and clinical recovery in patients with moderate to severe COVID-19.
33078827 As a result, anti-HIV or antiviral drugs (lopinavir, tenofovir disoproxil, fosamprenavir and ganciclovir), antiflu drugs (peramivir and zanamivir) and an anti-HCV drug (sofosbuvir) are predicted to bind to 3CLPro in SARS-CoV-2 with therapeutic potential for COVID-19 infection by our new protocol.
33080984 We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 infection in human cervical TZM-bl cells.
33122172 Of significance, sofosbuvir demonstrated no antiviral effect against CoV-2, and its triphosphate did not inhibit CoV-2 RNA polymerase.
33124786 Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2. […] Here, using model polymerase extension experiments, we demonstrate that the active triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the active triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase.
33217430 Upon transfection, the replicon RNA replicated in various cell lines, and was sensitive to interferon alpha (IFN-α), remdesivir, but was resistant to hepatitis C virus inhibitors daclatasvir and sofosbuvir.
33287144 In recent years, RdRp has emerged as an optimal target for the development of antiviral drugs, as demonstrated by recent approvals of sofosbuvir and remdesivir against Hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively.
33338232 This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection. […] Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. […] Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). […] One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. […] After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001. […] In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. […] Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. […] Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month.
33362383 Drugs suitable to manage COVID-19 in patients with liver disease might include remdesivir intravenously, nitazoxanide + sofosbuvir, ivermectin, tocilizumab, convalescent plasma, and low molecular weight heparin in certain situations.
33372806 A hit list of 7 compounds alongside two positive controls (remdesivir and sofosbuvir) and two negative controls (cinnamaldehyde and Thymoquinone) were further docked into the active site of 8 different conformations of SARS-CoV-2 RdRp gotten from molecular dynamics simulation (MDS) system equilibration. […] These phytochemicals, in addition to other promising antivirals such as remdesivir and sofosbuvir, may be exploited towards the development of a cocktail of anti-coronavirus treatments in COVID-19.
33378357 In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients.
33389441 In this study, detailed molecular docking and dynamics simulations are used to evaluate the binding affinity of a clinically approved drug, sofosbuvir, with the solved structure of the viral protein RNA-dependent RNA polymerase (RdRp) and compare it to the clinically approved drug, Remdesivir. […] Sofosbuvir is a drug that is currently used for HCV treatment; therefore, HCV RdRp is used as a positive control protein target. […] The interaction of SARS-CoV-2 RdRp as a target with the active form of sofosbuvir as a ligand demonstrates binding effectiveness. […] One of the FDA-approved antiviral drugs, such as sofosbuvir, can help us in this mission, aiming to limit the danger of COVID-19. […] Sofosbuvir was found to bind nsp12 with comparable binding energies to that of Remdesivir, which has been reported for its potential against COVID-19 RdRp and is currently approved by the FDA.
33505872 The nucleotide inhibitors such as sofosbuvir, ribavirin, galidesivir, remdesivir, favipiravir, cefuroxime, tenofovir, and hydroxychloroquine (HCHL), setrobuvir, YAK, and IDX-184 were found to be effective in binding to SARS-CoV-2 RNA-dependent RNA polymerase.