Vismodegib for COVID-19

Papain-like protease (PLpro) is a crucial enzyme for SARS-CoV-2 replication and immune evasion. Inhibiting PLpro could be a promising strategy to fight against COVID-19. This study aimed to identify potent inhibitors of PLpro among FDA-approved drugs using an in silico approach. The study also aimed to examine and confirm the binding of the selected compounds to the active pocket of PLpro using a multi-phased in silico approach, involving the screening of 3009 FDA-approved drugs to pinpoint the most similar compounds to, TTT, the co-crystallized ligand TTT of PLpro. The selected compounds were subjected to further analysis, including molecular docking, molecular dynamics simulations, MM-GPSA (molecular mechanics generalized Born surface area), and PLIP (Protein-Ligand Interaction Profiler) studies, to examine and confirm their binding to the active pocket of PLpro. Seven candidates (Vismodegib, Celecoxib, Ketoprofen, Indomethacin, Naphazoline, Valdecoxib, and Eslicarbazepine) showed promising in silico activities against the PLpro. The computational analysis confirmed the binding of Celecoxib to the active pocket of PLpro, suggesting its potential in the fight against COVID-19. This study identified seven FDA-approved drugs as potential inhibitors of PLpro, providing a feasible approach for drug repurposing against COVID-19. The results obtained from the in silico approach hold promise, but further in vitro and in vivo studies are warranted to validate the potential of these compounds.

AbstractTo identify potential therapeutic stop-gaps for SARS-CoV-2, we evaluated a library of 1,670 approved and reference compounds in an unbiased, cellular image-based screen for their ability to suppress the broad impacts of the SARS-CoV-2 virus on phenomic profiles of human renal cortical epithelial cells using deep learning. In our assay, remdesivir is the only antiviral tested with strong efficacy, neither chloroquine nor hydroxychloroquine have any beneficial effect in this human cell model, and a small number of compounds not currently being pursued clinically for SARS-CoV-2 have efficacy. We observed weak but beneficial class effects of β-blockers, mTOR/PI3K inhibitors and Vitamin D analogues and a mild amplification of the viral phenotype with β-agonists.

Context: The whole universe is facing a coronavirus catastrophe, and prompt treatment for the health crisis is primarily significant. The primary way to improve health conditions in this battle is to boost our immunity and alter our diet patterns. A common bulb veggie used to flavor cuisine is garlic. Compounds in the plant that are physiologically active are present, contributing to its pharmacological characteristics. Among several food items with nutritional value and immunity improvement, garlic stood predominant and more resourceful natural antibiotic with a broad spectrum of antiviral potency against diverse viruses. However, earlier reports have depicted its efficacy in the treatment of a variety of viral illnesses. Nonetheless, there is no information on its antiviral activities and underlying molecular mechanisms. Objectives: The bioactive compounds in garlic include organosulfur (allicin and alliin) and flavonoid (quercetin) compounds. These compounds have shown immunomodulatory effects and inhibited attachment of coronavirus to the angiotensin-converting enzyme 2 (ACE2) receptor and the Mpro of SARS-CoV-2. Further, we have discussed the contradictory impacts of garlic used as a preventive measure against the novel coronavirus. Method: The GC/MS analysis revealed 18 active chemicals, including 17 organosulfur compounds in garlic. Using the molecular docking technique, we report for the first time the inhibitory effect of the under-consideration compounds on the host receptor ACE2 protein in the human body, providing a crucial foundation for understanding individual compound coronavirus resistance on the main protease protein of SARS-CoV-2. Allyl disulfide and allyl trisulfide, which make up the majority of the compounds in garlic, exhibit the most potent activity. Results: Conventional medicine has proven its efficiency from ancient times. Currently, our article's prime spotlight was on the activity of Allium sativum on the relegation of viral load and further highlighted artificial intelligence technology to study the attachment of the allicin compound to the SARS-CoV-2 receptor to reveal its efficacy. Conclusions: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.