LitCovid-sentences  

PMC:7600245 / 7708-14062 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T56 0-4 Sentence denotes 2.1.
T57 5-34 Sentence denotes Remdesivir (Veklury, GS-5734)
T58 35-137 Sentence denotes Remdesivir is an adenosine monophosphate derivative and nucleotide-based antiviral prodrug (Figure 2).
T59 138-216 Sentence denotes Remdesivir received, in May 2020, an emergency use authorization from the U.S.
T60 217-354 Sentence denotes FDA for the treatment of laboratory-confirmed or suspected COVID-19 illness in children and adults hospitalized with severe disease [25].
T61 355-482 Sentence denotes The parenterally administered drug is being developed by Gilead Sciences, U.S., and has broad-spectrum antiviral activity [26].
T62 483-558 Sentence denotes It was first studied in 2016 as a potential treatment for Ebola virus [27].
T63 559-727 Sentence denotes In addition to its activity against SARS-CoV-2, remdesivir has a potential to treat a variety of infections caused by RNA viruses, including SARS-CoV and MERS-CoV [28].
T64 728-865 Sentence denotes The drug is metabolized to the pharmacologically active nucleoside triphosphate metabolite after being distributed into cells (Figure 2).
T65 866-1038 Sentence denotes The triphosphate metabolite acts as a competitive inhibitor of RdRp and thus eventually causes chain elongation termination, which decreases the viral RNA replication [29].
T66 1039-1135 Sentence denotes The termination is delayed and happens after the addition of more nucleotides (between 3 and 5).
T67 1136-1244 Sentence denotes Therefore, remdesivir is described as a direct antiviral agent acting as a delayed chain terminator [30,31].
T68 1245-1322 Sentence denotes Importantly, remdesivir avoids proofreading by viral exoribonuclease [28,32].
T69 1323-1438 Sentence denotes Currently, remdesivir is being evaluated as a treatment for COVID-19 patients in about 15 studies across the globe.
T70 1439-1620 Sentence denotes The drug is being tested alone or in combination with merimepodib (NCT04410354; n = 40), tocilizumab (NCT04409262; REMDACTA; n = 450), or baricitinib (NCT04401579; ACTT2; n = 1034).
T71 1621-1732 Sentence denotes In particular, merimepodib is another antiviral agent that is inhibitor of inosine monophosphate dehydrogenase.
T72 1733-1797 Sentence denotes The enzyme is required for the synthesis of guanine nucleotides.
T73 1798-1913 Sentence denotes Merimepodib consequently inhibits the synthesis of DNA and RNA, leading to antiviral and immunosuppressive effects.
T74 1914-2018 Sentence denotes Thus, remdesivir and merimepodib is a dual-acting antiviral combination with immunosuppressive activity.
T75 2019-2166 Sentence denotes Remdesivir itself demonstrated in vitro activity against Vero E6 cells infected with SARS-CoV-2 with an EC50 value of 0.77 µM (CC50 > 100 µM) [33].
T76 2167-2364 Sentence denotes Remdesivir also exhibited in vitro activity against SARS-CoV and MERS-CoV in multiple in vitro systems, including primary human airway epithelial cell cultures with sub-micromolar IC50 values [28].
T77 2365-2567 Sentence denotes Remdesivir was also effective against pre-pandemic bat-CoVs, bat-CoVs, and contemporary circulating human coronaviruses in primary human lung cells suggesting a broad-spectrum anti-coronavirus activity.
T78 2568-2796 Sentence denotes In a mouse model of SARS-CoV, the prophylactic and early therapeutic use of remdesivir significantly decreased the lung viral load and improved the respiratory functions as well as the overall clinical signs of the disease [28].
T79 2797-2936 Sentence denotes Furthermore, remdesivir with interferon (INF)-b demonstrated better antiviral activity compared to lopinavir/ritonavir with INF-b in vitro.
T80 2937-3153 Sentence denotes Compared to lopinavir/ritonavir/INF-b, the prophylactic and therapeutic use of remdesivir also more effectively diminished the pulmonary viral loads and improved the pulmonary function in mice model of MERS-CoV [34].
T81 3154-3298 Sentence denotes The efficacy of the prophylactic and therapeutic use of remdesivir was also demonstrated in the rhesus macaque model of MERS-CoV infection [35].
T82 3299-3456 Sentence denotes Very recently, remdesivir was also shown to inhibit SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM).
T83 3457-3654 Sentence denotes In mice infected with a chimeric SARS-CoV encoding RdRp, therapeutic administration of remdesivir diminished lung viral load and improved pulmonary function compared with vehicle-treated mice [36].
T84 3655-4008 Sentence denotes As far as clinical trials in humans, a randomized, placebo-controlled, double-blind trial in hospitalized adults (n = 236) with severe COVID-19 in China initially revealed that the median time to improvement was not substantially different in the remdesivir group (200 mg on the first day, and then 100 mg/day for 9 days) from that of the placebo group.
T85 4009-4068 Sentence denotes The mortality rate was also similar in the two groups [37].
T86 4069-4132 Sentence denotes Yet, the trial was criticized for being insufficiently powered.
T87 4133-4411 Sentence denotes Later, a phase 3 randomized, open-label trial in adults (n = 397) hospitalized with severe COVID-19 sponsored by Gilead revealed that the time to clinical improvement for 50% of patients was 10 days in the 5-day treatment group relative to 11 days in the 10-day treatment group.
T88 4412-4504 Sentence denotes The dose regimen used was 200 mg on day 1, followed by 100 mg/day for total of 5 or 10 days.
T89 4505-4636 Sentence denotes At day 14, about 64.5% of the patients in the 5-day group and 53.8% of the patients in the 10-day group achieved clinical recovery.
T90 4637-4795 Sentence denotes Patients treated with remdesivir within 10 days of symptoms onset achieved better outcomes relative to those treated after more than 10 days of symptoms [38].
T91 4796-4897 Sentence denotes Similar results were obtained in hospitalized adults (n = 1600) with moderate COVID-19 (NCT04292730).
T92 4898-5040 Sentence denotes In an uncontrolled study of hospitalized COVID-19 patients (n = 61), most patients needed less oxygen support after receiving remdesivir [39].
T93 5041-5132 Sentence denotes Importantly, a phase 3 adaptive, randomized, placebo-controlled study sponsored by the U.S.
T94 5133-5498 Sentence denotes National Institute of Allergy and Infectious Diseases (NIAID) in hospitalized adults (n = 1063) indicated that: (a) the patients in the remdesivir group had shorter median time to recovery (11 days) than the patients in the placebo group (15 days) and (b) remdesivir may decrease the mortality rate from 11.6% in the placebo group to 8% in the treatment group [40].
T95 5499-5561 Sentence denotes As of now, the COVID-19 Treatment Guidelines Panel of the U.S.
T96 5562-5788 Sentence denotes National Institute of Health recommends remdesivir for the treatment of COVID-19 in hospitalized patients with severe disease (requiring supplemental oxygen or on mechanical ventilation or extracorporeal membrane oxygenation).
T97 5789-5953 Sentence denotes The Panel also indicates that there are no sufficient data to recommend either for or against the use of remdesivir in patients with mild or moderate COVID-19 [41].
T98 5954-5971 Sentence denotes Of note, the U.S.
T99 5972-6176 Sentence denotes FDA warns against the concomitant use of remdesivir and chloroquine or hydroxychloroquine owing to in vitro evidence which suggests that chloroquine blocks the intracellular activation of remdesivir [42].
T100 6177-6354 Sentence denotes Moreover, data from the manufacturer’s compassionate use program suggested no safety concerns were identified for remdesivir in pediatric, pregnant, or postpartum patients [43].