Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19

Barratt‐Due, Andreas; Olsen, Inge Christoffer; Nezvalová-Henriksen, Kateřina; Kåsine, Trine; Lund-Johansen, Fridtjof; Hoel, Hedda; Holten, Aleksander Rygh; Tveita, Anders Aune; Mathiessen, Alexander; Haugli, Mette; Eiken, Ragnhild; Kildal, Anders Benjamin; Berg, Åse; Johannessen, Asgeir; Heggelund, Lars; Dahl, Tuva B.; Skåra, Karoline H; Mielnik, Paweł; Le, Lan Ai Kieu; Thoresen, Lars; Ernst, Gernot; Hoff, Dag Arne Lihaug; Skudal, Hilde; Kittang, Bård Reiakvam; Olsen, Roy Bjørkholt; Tholin, Birgitte; Ystrøm, Carl Magnus; Skei, Nina Vibeche; Tran, Trung; Dudman, Susanne; Andersen, Jan Terje; Hannula, Raisa; Dalgård, Olav; Finbråten, Ane‐Kristine; Tonby, Kristian; Blomberg, Björn; Aballi, Saad; Fladeby, Cathrine; Steffensen, Anne Katrine; Müller, Fredrik; Dyrhol‐Riise, Anne Ma; Trøseid, Marius; Aukrust, Pål

doi:10.7326/m21-0653

Cited by 92 publications

(127 citation statements)

References 18 publications

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“…Although their administration clinically improved the recovery rate of patients, they were ineffective in reducing the mortality rate. Moreover, favipiravir was contraindicated due to the teratogenic and embryotoxic effects on animals [28][29][30]. Thus, the development of more effective therapeutic agents is crucial.…”

Section: Discussionmentioning

confidence: 99%

Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor

Kim

Chung

Noh

et al. 2021

IJMS

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The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. Geraniin also demonstrated a high affinity to both proteins despite a relatively lower equilibrium dissociation constant (KD) for the spike protein (0.63 μM) than hACE2 receptor (1.12 μM), according to biolayer interferometry-based analysis. In silico analysis indicated geraniin’s interaction with the residues functionally important in the binding between the two proteins. Thus, geraniin is a promising therapeutic agent for COVID-19 by blocking SARS-CoV-2’s entry into human cells.

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Section: Discussionmentioning

confidence: 99%

Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor

Kim

Chung

Noh

et al. 2021

IJMS

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“…NOR-Solidarity is a multicentre, open label, adaptive randomised clinical trial evaluating the effect of antiviral drugs on hospitalized COVID-19 patients admitted to 23 Norwegian hospitals(12). In addition, NOR-Solidarity included collections of blood biobank and outpatient visits at a three-month follow-up after hospital admission.…”

Section: Methodsmentioning

confidence: 99%

“…Participants were included from March 28 th until October 5 th 2020, and all participants >18 years admitted to the hospital with PCR-confirmed SARS-2-CoV-2 infection were eligible for inclusion. Exclusion criteria are described in the original study protocol and included severe comorbidity (life expectancy < 3 months), high levels of liver transaminases (AST/ALT > 5 times upper limit of normal), corrected QT interval time as assessed by ECG more than 470 ms, pregnancy, breast feeding, acute comorbidity occurrence in a 7-day period before inclusion, known intolerance to study drugs, concomitant medications interfering with the study drugs or participation in a confounding trial(12). All participants gave informed consent prior to inclusion, either by themselves or a legally authorised representative.…”

Section: Methodsmentioning

confidence: 99%

“…All study treatments were stopped at hospital discharge. Since the interventions had no effect on clinical outcome, viral clearance or systemic inflammation(12), data from the different intervention arms were in this sub-study pooled for analyses to examine whether gut microbiota composition after three months and markers of gut barrier dysfunction during hospitalization and after three months had any effect on:(i) acute respiratory failure defined as pO 2 /fiO 2 -(P/F-ratio) <26.6 kPa (<200 mmHg) during hospitalization, (ii) persistent respiratory dysfunction defined as diffusing capacity of the lungs for carbon monoxide (DL CO ) below the lower limit of normal (LLN) at the three-month follow-up. To ensure lack of influence of different treatment, data were also adjusted for treatment group.…”

Section: Methodsmentioning

confidence: 99%

“…The NOR-Solidarity trial is an independent add-on study to the WHO Solidarity trial(11), recently reporting no effects of hydroxychloroquine (HCQ) or remdesivir compared to standard of care (SoC) on clinical outcome, viral clearance or systemic inflammation in hospitalized COVID-19 patients(12). In the present sub-study, we investigated whether gut microbiota collected three months after hospital admission, as well markers of gut barrier dysfunction measured during and after hospitalization, were related to persistent pulmonary dysfunction after COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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Gut microbiota alterations in patients with persistent respiratory dysfunction three months after severe COVID-19

Vestad

Ueland

Lerum

et al. 2021

Preprint

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Objective: Although COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and could be related to long-term respiratory dysfunction is unknown. Design: From the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DLCO), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with persistent respiratory dysfunction, defined as DLCO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella, the latter potentially being linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2-(P/F-ratio)<26.6 kPa. LBP levels remained elevated during and after hospitalization, and was associated with low-grade inflammation and persistent respiratory dysfunction after three months. Conclusion: Persistent respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

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Remdesivir for the treatment of COVID-19

Ansems

Grundeis

Dahms

et al. 2021

Cochrane Database of Systematic Reviews

105

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Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19

Abstract: In an add-on study of the WHO Solidarity trial, Norwegian investigators examined the effect of remdesivir and hydroxychloroquine on the degree of clinical respiratory failure, on SARS-CoV-2 viral load in the oropharynx, and on levels of inflammatory variables in plasma or serum.

Cited by 92 publications

References 18 publications

Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor

Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor

Gut microbiota alterations in patients with persistent respiratory dysfunction three months after severe COVID-19

Remdesivir for the treatment of COVID-19

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