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Gliquidone for COVID-19

Gliquidone has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Onyango, O., In Silico Models for Anti-COVID-19 Drug Discovery: A Systematic Review, Advances in Pharmacological and Pharmaceutical Sciences, doi:10.1155/2023/4562974
The coronavirus disease 2019 (COVID-19) is a severe worldwide pandemic. Due to the emergence of various SARS-CoV-2 variants and the presence of only one Food and Drug Administration (FDA) approved anti-COVID-19 drug (remdesivir), the disease remains a mindboggling global public health problem. Developing anti-COVID-19 drug candidates that are effective against SARS-CoV-2 and its various variants is a pressing need that should be satisfied. This systematic review assesses the existing literature that used in silico models during the discovery procedure of anti-COVID-19 drugs. Cochrane Library, Science Direct, Google Scholar, and PubMed were used to conduct a literature search to find the relevant articles utilizing the search terms “In silico model,” “COVID-19,” “Anti-COVID-19 drug,” “Drug discovery,” “Computational drug designing,” and “Computer-aided drug design.” Studies published in English between 2019 and December 2022 were included in the systematic review. From the 1120 articles retrieved from the databases and reference lists, only 33 were included in the review after the removal of duplicates, screening, and eligibility assessment. Most of the articles are studies that use SARS-CoV-2 proteins as drug targets. Both ligand-based and structure-based methods were utilized to obtain lead anti-COVID-19 drug candidates. Sixteen articles also assessed absorption, distribution, metabolism, excretion, toxicity (ADMET), and drug-likeness properties. Confirmation of the inhibitory ability of the candidate leads by in vivo or in vitro assays was reported in only five articles. Virtual screening, molecular docking (MD), and molecular dynamics simulation (MDS) emerged as the most commonly utilized in silico models for anti-COVID-19 drug discovery.
Shen et al., The antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients, Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2023.1141274
IntroductionWith the emergence of SARS-CoV-2 mutant strains, especially the epidemic of Omicron, it continues to evolve to strengthen immune evasion. Omicron BQ. 1 and XBB pose a serious threat to the current COVID-19 vaccine (including bivalent mRNA vaccine for mutant strains) and COVID-19-positive survivors, and all current therapeutic monoclonal antibodies are ineffective against them. Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalization and death after the initial vaccine booster. However, small-molecule drugs for conserved targets remain effective and urgently needed.MethodsThe non-structural protein of SARS-CoV-2 non-structural protein 1(Nsp1) can bind to the host 40S ribosomal subunit and activate the nuclease to hydrolyze the host RNA, while the viral RNA is unaffected, thus hijacking the host system. First, the present study analyzed mutations in the Nsp1 protein and then constructed a maximum-likelihood phylogenetic tree. A virtual drug screening method based on the Nsp1 structure (Protein Data Bank ID: 7K5I) was constructed, 7495 compounds from three databases were collected for molecular docking and virtual screening, and the binding free energy was calculated by the MM/GBSA method.ResultsOur study shows that Nsp1 is relatively conserved and can be used as a comparatively fixed drug target and that therapies against Nsp1 will target all of these variants. Golvatinib, Gliquidone, and Dihydroergotamine were superior to other compounds in the crystal structure of binding conformation and free energy. All effectively interfered with Nsp1 binding to 40S protein, confirming the potential inhibitory effect of these three compounds on SARS-CoV-2.DiscussionIn particular, Golwatinib provides a candidate for treatment and prophylaxis in elderly patients with Omicjon, suggesting further evaluation of the anti-SARS-CoV-2 activity of these compounds in cell culture. Further studies are needed to determine the utility of this finding through prospective clinical trials and identify other meaningful drug combinations.
Rudramurthy et al., In-Vitro Screening of Repurposed Drug Library against Severe Acute Respiratory Syndrome Coronavirus-2, Medical Research Archives, doi:10.18103/mra.v11i2.3595
The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demands rapid identification of new antiviral molecules from the existing drugs. Drug repurposing is a significant alternative for pandemics and emerging diseases because of the availability of preclinical data, documented safety in clinic and possibility of immediate production and scalable capacity and supply. Several drugs such as ivermectin and hydroxy chloroquine have been repurposed as anti-SARS-CoV-2 agents, but the effect of these compounds in treating the COVID-19 patients remains sub-optimal. In the present study repurposed drug libraries consisting of 560 compounds from two different sources have been screened against SARS-CoV-2 isolate USA-WA1/2020 in Vero-E6 cell line and 24 compounds were found active. The SARS-CoV-2 virus propagated in Vero E6 cell line and used in screening the drug libraries was sequenced by Next Generation Sequencing to identify any mutations that may have accumulated in the virus genome. The whole genome sequencing data of SARS-CoV-2 showed 9 and 6 single nucleotide polymorphisms in spike protein with reference to Wuhan-Hu-1(NC045512.2) and USA/WA-CDC-WA1/2020 (MN985325.1) isolates respectively. The present study identified 24 compounds active against SARS-CoV-2 isolate USA-WA1/2020 out of 560 repurposed drugs from two libraries. The IC-50 values of the identified hits range from 0.4 µM to 16 µM. Further studies on the repurposed drugs identified in the present screen may be helpful in the rapid development of antiviral drugs against SARS-CoV-2.
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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