Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial

Kasgari, Hamideh Abbaspour; Moradi, Siavash; Shabani, Amir; Babamahmoodi, Farhang; Badabi, Ali Reza Davoudi; Davoudi, Lotfollah; Alikhani, Ahmad; Omran, Akbar Hedayatizadeh; Saeedi, Majid; Merat, Shahin; Wentzel, Hannah; Garratt, Anna; Levi, Jacob; Simmons, Bryony; Hill, Andrew; Fakheri, Hafez

doi:10.1093/jac/dkaa332

Cited by 79 publications

(80 citation statements)

References 27 publications

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“…59 These investigators showed that SOF/DCV treatment increased 14-day clinical recovery rates and reduced hospital stays. Two similar SOF/DCV clinical trials were also performed and provided evidence that this drug combination may have some benefit; 60,61 the authors recommended that larger well-controlled randomized trials are necessary to confirm their results. Indeed, a network of larger COVID-19 clinical trials has been established in Brazil, Egypt, Iran, and South Africa.…”

Section: F I G U R E 4 Incorporation Of 2'-fme-utp 3'-f-dttp and 3'mentioning

confidence: 99%

Nucleotide analogues as inhibitors of SARS‐CoV Polymerase

Kumar

et al. 2020

Pharmacology Res & Perspec

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SARS‐CoV‐2, a member of the coronavirus family, has caused a global public health emergency. 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. Using the same molecular insight, we selected 3’‐fluoro‐3’‐deoxythymidine triphosphate and 3’‐azido‐3’‐deoxythymidine triphosphate, which are the active forms of two other anti‐viral agents, Alovudine and AZT (an FDA‐approved HIV/AIDS drug) for evaluation as inhibitors of SARS‐CoV RdRp. We demonstrate the ability of two of these HIV reverse transcriptase inhibitors to be incorporated by SARS‐CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS‐CoV and SARS‐CoV‐2 RdRps, we expect these nucleotide analogues would also inhibit the SARS‐CoV‐2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad‐spectrum anti‐coronavirus agents.

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Section: F I G U R E 4 Incorporation Of 2'-fme-utp 3'-f-dttp and 3'mentioning

confidence: 99%

Nucleotide analogues as inhibitors of SARS‐CoV Polymerase

Kumar

et al. 2020

Pharmacology Res & Perspec

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“…However, some secondary endpoints provided evidences to support the efficacy, e.g. Sodeghi et al 55 showed hospital stay was significantly shorter and the rate of discharge was significantly higher in the combined therapy group, and Kasgari et al 56 showed the clinical recovery status was significantly better in the combined treatment group. Addition of ribavirin onto the sofosbuvir and daclatasvir seemed not to have shown any evidences suggesting increased benefit.…”

Section: Efficacy and Safety Of Combined Antiviral Agentsmentioning

confidence: 99%

Progresses in clinical studies on antiviral therapies for COVID‐19—Experience and lessons in design of clinical trials

Zhaori

Liu

et al. 2020

Pediatric Investigation

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Antiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease (COVID‐19) caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID‐19 during the pandemic of this disease. We need to answer the following questions: do we still need to use rigorously designed randomized controlled clinical trials (RCTs)? Or, will it be enough if we use loosened criteria, observational studies or even retrospective case series and case reports? The answer is “No, we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents.” In this article, we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID‐19, and found that among the reports on monotherapies, only remdesivir, and among combined antiviral agents, only the combined regimen with interferon‐β1b, lopinavir‐ritonavir and ribavirin were effective and safe based on evidences from RCTs. The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID‐19, especially at larger doses. Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed, discussed and emphasized from the specific requirements and considerations of antiviral therapies. We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.

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“…44 In a prospective, open-label, randomized, phase 2 trial in adults with COVID-19 ribavirin was used in combination with Interferon β-1b and lopinavir/ritonavir as triple therapy. 45 The triple therapy group had a significantly shorter median time from the start of study treatment to negative nasopharyngeal swab (7 days) than the control group ( [47][48][49] Limitations to these studies are the small sample sizes, as well as all studies being from one region. Therefore, more research is needed to evaluate their true benefits.…”

Section: Ribavirinmentioning

confidence: 99%

Pharmacological treatment of COVID-19: an update

Onwudiwe

Weli

Shaanu

et al. 2020

Journal of Global Health Reports

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Background Background The ongoing coronavirus disease-19 (COVID-19) pandemic, caused by the novel coronavirus 2 (SARS-CoV-2) has triggered a worldwide search for medications addressing the morbidity and mortality associated with it. Various medications have been proposed and applied to control COVID-19 based on previous experiences with other viral infections. Some of these have been shown to be harmful or lack efficacy. This review discusses the medications that have been repurposed for SARS-CoV-2, experimental medications undergoing clinical trials, as well as the regional variations in COVID-19 treatments. Methods Methods A literature search was conducted to cover the period of January 2020 to September 2020 using the keywords "medications, treatment, therapeutics, pharmacological management for COVID-19" in various combinations as search strings. PubMed, LitCOVID, Google Scholar, Science Direct, and clinicaltrials.gov were the databases utilized. Results Results Evidence from ongoing clinical trials has shown promise with antiviral medications such as remdesivir, as well as corticosteroids, and convalescent plasma for severe cases of COVID-19. There is still, however, some conflicting evidence on the true benefits of these treatments. Other medications such as interferons, monoclonal antibodies, immune modulators, do not have enough clinical evidence of their safety and efficacy in COVID-19 patients for their recommended use. The role of anticoagulants and pulmonary vasodilators is still being explored. The efficacy of hydroxychloroquine is yet to be demonstrated in COVID-19 patients and is currently no longer recommended. Experimental medications targeting specific viral proteases are future promising therapies. Conclusions Conclusions The retinue of medications being used to treat COVID-19 is evolving and expanding as more clinical trials provide results. Several potential medication therapies are currently being investigated. While awaiting an approved safe and efficacious medication to treat this virus, a periodic review of ongoing research is highly encouraged.

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Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial

Cited by 79 publications

References 27 publications

Nucleotide analogues as inhibitors of SARS‐CoV Polymerase

Nucleotide analogues as inhibitors of SARS‐CoV Polymerase

Progresses in clinical studies on antiviral therapies for COVID‐19—Experience and lessons in design of clinical trials

Pharmacological treatment of COVID-19: an update

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