Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Ye, Wei; Yao, Min; Dong, Yangchao; Ye, Chuantao; Wang, Dan; Li, He; Ma, Heng; Zhang, Hui; Qi, Libin; Yang, Yuewu; Wang, Yuan; Zhang, Liang; Cheng, Long; Lv, Xin; Zhang, Xu; Lei, Yingfeng; Zhang, Fanglin

doi:10.3389/fmicb.2020.01105

Cited by 28 publications

(19 citation statements)

References 30 publications

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“…This is reflected in multiple clinical practice guidelines that almost exclusively recommend supportive therapy alone, outside the context of a clinical trial 234. Remdesivir is a novel monophosphoramidate adenosine analogue prodrug that impedes viral RNA synthesis and has in vitro antiviral activity against several viral agents 5. Two recently published clinical practice guidelines have addressed remdesivir, both with recommendations for administration (table 1).…”

mentioning

confidence: 99%

Remdesivir for severe covid-19: a clinical practice guideline

Rochwerg

Agarwal

Zeng

et al. 2020

BMJ

102

118

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Clinical questionWhat is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020.Current practiceRemdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice.RecommendationsThe guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir.How this guideline was createdAn international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems.The evidenceThe linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay.Understanding the recommendationMost patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.

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mentioning

confidence: 99%

Remdesivir for severe covid-19: a clinical practice guideline

Rochwerg

Agarwal

Zeng

et al. 2020

BMJ

102

118

View full text Add to dashboard Cite

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“…Due to this mechanism, Remdesivir confuses viral RNA-dependent RNA polymerase and delays, or prematurely terminates, RNA chains which in turn inhibits viral RNA production and replication of EBOV [65,66]. Viruses with mutated RNA polymerase often develop partial resistance against Remdesivir [67,68]. Recent research has demonstrated that Remdesivir is a potential therapeutic for the treatment of SARS-CoV-2.…”

Section: Potential Treatment Strategiesmentioning

confidence: 99%

COVID-19: Characteristics and Therapeutics

Chilamakuri

Agarwal

2021

Cells

228

197

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Novel coronavirus (COVID-19 or 2019-nCoV or SARS-CoV-2), which suddenly emerged in December 2019 is still haunting the entire human race and has affected not only the healthcare system but also the global socioeconomic balances. COVID-19 was quickly designated as a global pandemic by the World Health Organization as there have been about 98.0 million confirmed cases and about 2.0 million confirmed deaths, as of January 2021. Although, our understanding of COVID-19 has significantly increased since its outbreak, and multiple treatment approaches and pharmacological interventions have been tested or are currently under development to mitigate its risk-factors. Recently, some vaccine candidates showed around 95% clinical efficacy, and now receiving emergency use approvals in different countries. US FDA recently approved BNT162 and mRNA-1273 vaccines developed by Pfizer/BioNTech and Moderna Inc. for emergency use and vaccination in the USA. In this review, we present a succinct overview of the SARS-CoV-2 virus structure, molecular mechanisms of infection, COVID-19 epidemiology, diagnosis, and clinical manifestations. We also systematize different treatment strategies and clinical trials initiated after the pandemic outbreak, based on viral infection and replication mechanisms. Additionally, we reviewed the novel pharmacological intervention approaches and vaccine development strategies against COVID-19. We speculate that the current pandemic emergency will trigger detailed studies of coronaviruses, their mechanism of infection, development of systematic drug repurposing approaches, and novel drug discoveries for current and future pandemic outbreaks.

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“…Few possible antiviral medications are being immediately prescribed to COVID-19 patients during the pandemic ( Table 2 ). Remdesivir (GS-5734) may be an adenosine nucleotide 1’-cyano-substituted analog prodrug and demonstrated large-spectrum antiviral activity against so many RNA viruses ( Ye et al, 2020 ; Matthias, 2021 ). Based on evidence from an in vitro cell line and a mouse model, Remdesivir can inhibit the NSP12 polymerase even when ExoN proofreading activity is perfect ( Agostini et al, 2018 ).…”

Section: Potential Strategies To Treat Covid-19mentioning

confidence: 99%

COVID-19 and SARS-CoV-2 Variants: Current Challenges and Health Concern

et al. 2021

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The ongoing coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, was triggered and unfolded quickly throughout the globe by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new virus, transmitted primarily through inhalation or contact with infected droplets, seems very contagious and pathogenic, with an incubation period varying from 2 to 14 days. The epidemic is an ongoing public health problem that challenges the present global health system. A worldwide social and economic stress has been observed. The transitional source of origin and its transport to humans is unknown, but speedy human transportation has been accepted extensively. The typical clinical symptoms of COVID-19 are almost like colds. With case fatality rates varying from 2 to 3 percent, a small number of patients may experience serious health problems or even die. To date, there is a limited number of antiviral agents or vaccines for the treatment of COVID-19. The occurrence and pathogenicity of COVID-19 infection are outlined and comparatively analyzed, given the outbreak’s urgency. The recent developments in diagnostics, treatment, and marketed vaccine are discussed to deal with this viral outbreak. Now the scientist is concerned about the appearance of several variants over the globe and the efficacy of the vaccine against these variants. There is a need for consistent monitoring of the virus epidemiology and surveillance of the ongoing variant and related disease severity.

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Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Cited by 28 publications

References 30 publications

Remdesivir for severe covid-19: a clinical practice guideline

Remdesivir for severe covid-19: a clinical practice guideline

COVID-19: Characteristics and Therapeutics

COVID-19 and SARS-CoV-2 Variants: Current Challenges and Health Concern

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