A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

Mulangu, Sabue; Le, Dodd; Rt, Davey; O, Tshiani Mbaya; Proschan, Michael A.; Mukadi, Daniel; M, Lusakibanza Manzo; Nzolo, Didier; A, Tshomba Oloma; Ibanda, A; Rabbani, Ali; Coulibaly, Siriman; Levine, Adam C.; Grais, Rebecca F.; Dı́az, Janet; Hc, Lane; Jj, Muyembe-Tamfum; Sivahera, Billy; Camara, Mohamed Seto; Kojan, Richard; Walker, Rebecca; Dighero-Kemp, Bonnie; H, Cao; Mukumbayi, Philippe; Mbala-Kingebeni, Placide; Ahuka, Steve; Albert, Sara; Bonnett, Tyler; Crozier, Ian; Duvenhage, Michael; Proffitt, Calvin; Teitelbaum, Marc; Moench, Thomas R.; Aboulhab, Jamila; Barrett, Kimberly T.; Cahill, Katherine N.; Cone, Katherine; Eckes, Risa; Hensley, Lisa E.; Herpin, Betsey; Higgs, Elizabeth; Ledgerwood, Julie E.; Pierson, Jerome F.; Smolskis, Mary; Sow, Yaya; Tierney, John; Sivapalasingam, Sumathi; Holman, Wayne; Gettinger, Nikki; Vallée, David; Nordwall, Jacqueline

doi:10.1056/nejmoa1910993

Cited by 1,261 publications

(1,103 citation statements)

References 12 publications

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“…At present, some drugs are effective in eliminating SARS-CoV-2 and improving symptoms. The most promising antiviral drug for SARS-CoV-2 is remdesivir that is currently under clinical development for the treatment of Ebola virus infection [11]. However, the efficacy and safety of remdesivir for SARS-CoV-2 pneumonia patients need to be assessed by further clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)

Hou

Huang

et al. 2020

Pharmacological Research

520

415

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Zifeng Yang). AbstractPurpose: Lianhuaqingwen (LH) as traditional Chinese medicine (TCM) formula has been used to treat influenza and exerted broad-spectrum antiviral effects on a series of influenza viruses and immune regulatory effects [1]. The goal of this study is to demonstrate the antiviral activity of LH against the novel SARS-CoV-2 virus and its potential effect in regulating host immune response. Methods: The antiviral activity of LH against SARS-CoV-2 was assessed in Vero E6 cells using CPE and plaque reduction assay. The effect of LH on virion morphology was visualized under transmission electron microscope. Pro-inflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. Results: LH significantly inhibited SARS-CoV-2 replication in Vero E6 cells and markedly reduced pro-inflammatory cytokines (TNF-α, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Furthermore, LH treatment resulted in abnormal particle morphology of virion in cells. J o u r n a l P r e -p r o o fConclusions: LH significantly inhibits the SARS-COV-2 replication, affects virus morphology and exerts anti-inflammatory activity in vitro. These findings indicate that LH protects against the virus attack, making its use a novel strategy for controlling the COVID-19 disease.

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Section: Introductionmentioning

confidence: 99%

Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)

Hou

Huang

et al. 2020

Pharmacological Research

520

415

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“…Broad spectrum antivirals or compounds with demonstrated activity against SARS-CoV or MERS-CoV are now considered for the treatment of infection caused by the novel coronavirus SARS-CoV-2. The nucleotide analog RDV has been tested in a randomized, controlled trial for Ebola virus disease (18). Although two other investigational therapies were more efficacious than RDV, an antiviral effect has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus

Gordon

Tchesnokov

Feng

et al. 2020

Journal of Biological Chemistry

721

736

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Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps).Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. Hence, https://www.jbc.org/cgi/

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“…Anecdotal cases have demonstrated the ability of lopinavir-ritonavir to J o u r n a l P r e -p r o o f Journal Pre-proof significantly reduce viral load and improve disease outcome [77]. In addition, remdesivir, an adenosine analogue currently under development for the management of Ebola virus infecti on [78], has been recently recognized as a promising antiviral therapy against a wide spectrum of RNA viruses [79] and showed good preliminary in vitro results in the control of SARS-CoV-2 infection [80]. Consequently, lopinavir-ritonavir and remdesevir are currently the only anti-viral drugs included in the more severe case management protocols of COVID-19 [10].…”

Section: The Management Of Covid-19: a Room For Anti-rheumatic Drugs?mentioning

confidence: 99%

COVID-19 infection and rheumatoid arthritis: Faraway, so close!

Favalli

Ingegnoli

Lucia

et al. 2020

Autoimmunity Reviews

407

438

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A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

Cited by 1,261 publications

References 12 publications

Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)

Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)

The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus

COVID-19 infection and rheumatoid arthritis: Faraway, so close!

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