Jun12162 for COVID-19

Jun12162 may be beneficial for COVID-19 according to the studies below. COVID-19 involves the interplay of 500+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 11,000+ potential treatments. c19early.org analyzes 220+ treatments. We have not reviewed Jun12162 in detail.
Nodola et al., Recent Advances in the Design of Inhibitors Targeting the Viral Entry and Replication of the SARS-CoV-2 Virus, Driven by In Silico Approaches, Molecules, doi:10.3390/molecules31162877
The SARS-CoV-2 pandemic has significantly impacted global health, politics, medicine, finance, and society. Since 2020, various mutations have been reported, leading to drug resistance in current treatments against different SARS-CoV-2 strains and a drastic increase in cases of long-COVID. This situation underscores the urgent need to develop targeted and effective drugs to combat the spread of SARS-CoV-2 strains and their mutants, manage long-COVID symptoms and prepare for future pandemics. Currently, the treatment of SARS-CoV-2 focuses on targeting the virus’s entry and replication mechanisms to disrupt its life cycle. This review examines approved drugs, clinical candidates, and inhibitors under development, along with their bioassay data, while highlighting associated challenges. It illustrates how inhibitors bind to active sites, providing insights and emphasizing the importance of in silico studies, such as molecular docking, molecular dynamics simulation, FEP+, WaterMap, and quantitative structure–activity relationship (QSAR) analyses, and their correlation with experimental studies in expediting the drug discovery process. The review aims to provide researchers with insights into the gaps that need to be addressed concerning mutations affecting viral entry and to prepare for future pandemics.
Tan et al., Design of SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model, bioRxiv, doi:10.1101/2023.12.01.569653
AbstractThe emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PLpro) is a promising but challenging drug target. In this study, we designed and synthesized 85 noncovalent PLproinhibitors that bind to the newly discovered Val70Ubsite and the known BL2 groove pocket. Potent compounds inhibited PLprowith inhibitory constant Kivalues from 13.2 to 88.2 nM. The co-crystal structures of PLprowith eight leads revealed their interaction modes. Thein vivoleadJun12682inhibited SARS-CoV-2 and its variants, including nirmatrelvir-resistant strains with EC50from 0.44 to 2.02 µM. Oral treatment withJun12682significantly improved survival and reduced lung viral loads and lesions in a SARS-CoV-2 infection mouse model, suggesting PLproinhibitors are promising oral SARS-CoV-2 antiviral candidates.One-Sentence SummaryStructure-guided design of SARS-CoV-2 PLproinhibitors within vivoantiviral efficacy in a mouse model.