Lovastatin for COVID-19
Lovastatin has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells, PLOS Pathogens, doi:10.1371/journal.ppat.1009840 ,
COVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, therapeutics that can help manage the disease are still required until immunity has been achieved globally. The identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARS-CoV-2-ΔOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were particularly effective in supporting SARS-CoV-2 replication, which is in-line with reported proteinuria and liver damage in patients with COVID-19. Using the nano-luciferase as a measure of virus replication we identified 35 drugs that reduced replication in Vero cells and human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3 to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected cells. In conclusion, our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID.
In Silico Identification and Analysis of Potentially Bioactive Antiviral Phytochemicals against SARS-CoV-2: A Molecular Docking and Dynamics Simulation Approach, BioMed Research International, doi:10.1155/2023/5469258 ,
SARS-CoV-2, a deadly coronavirus sparked COVID-19 pandemic around the globe. With an increased mutation rate, this infectious agent is highly transmissible inducing an escalated rate of infections and death everywhere. Hence, the discovery of a viable antiviral therapy option is urgent. Computational approaches have offered a revolutionary framework to identify novel antimicrobial treatment regimens and allow a quicker, cost-effective, and productive conversion into the health center by evaluating preliminary and safety investigations. The primary purpose of this research was to find plausible plant-derived antiviral small molecules to halt the viral entrance into individuals by clogging the adherence of Spike protein with human ACE2 receptor and to suppress their genome replication by obstructing the activity of Nsp3 (Nonstructural protein 3) and 3CLpro (main protease). An in-house library of 1163 phytochemicals were selected from the NPASS and PubChem databases for downstream analysis. Preliminary analysis with SwissADME and pkCSM revealed 149 finest small molecules from the large dataset. Virtual screening using the molecular docking scoring and the MM-GBSA data analysis revealed that three candidate ligands CHEMBL503 (Lovastatin), CHEMBL490355 (Sulfuretin), and CHEMBL4216332 (Grayanoside A) successfully formed docked complex within the active site of human ACE2 receptor, Nsp3, and 3CLpro, respectively. Dual method molecular dynamics (MD) simulation and post-MD MM-GBSA further confirmed efficient binding and stable interaction between the ligands and target proteins. Furthermore, biological activity spectra and molecular target analysis revealed that all three preselected phytochemicals were biologically active and safe for human use. Throughout the adopted methodology, all three therapeutic candidates significantly outperformed the control drugs (Molnupiravir and Paxlovid). Finally, our research implies that these SARS-CoV-2 protein antagonists might be viable therapeutic options. At the same time, enough wet lab evaluations would be needed to ensure the therapeutic potency of the recommended drug candidates for SARS-CoV-2.
Molecular-evaluated and explainable drug repurposing for COVID-19 using ensemble knowledge graph embedding, Scientific Reports, doi:10.1038/s41598-023-30095-z ,
AbstractThe search for an effective drug is still urgent for COVID-19 as no drug with proven clinical efficacy is available. Finding the new purpose of an approved or investigational drug, known as drug repurposing, has become increasingly popular in recent years. We propose here a new drug repurposing approach for COVID-19, based on knowledge graph (KG) embeddings. Our approach learns “ensemble embeddings” of entities and relations in a COVID-19 centric KG, in order to get a better latent representation of the graph elements. Ensemble KG-embeddings are subsequently used in a deep neural network trained for discovering potential drugs for COVID-19. Compared to related works, we retrieve more in-trial drugs among our top-ranked predictions, thus giving greater confidence in our prediction for out-of-trial drugs. For the first time to our knowledge, molecular docking is then used to evaluate the predictions obtained from drug repurposing using KG embedding. We show that Fosinopril is a potential ligand for the SARS-CoV-2 nsp13 target. We also provide explanations of our predictions thanks to rules extracted from the KG and instanciated by KG-derived explanatory paths. Molecular evaluation and explanatory paths bring reliability to our results and constitute new complementary and reusable methods for assessing KG-based drug repurposing.
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