Boceprevir for COVID-19
Boceprevir has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2, ACS Medicinal Chemistry Letters, doi:10.1021/acsmedchemlett.0c00521 ,
Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2021579118 ,
Significance COVID-19 is a global pandemic currently lacking an effective cure. We used a cell-based infection assay to screen more than 3,000 agents used in humans and animals and identified 15 with antiinfective activity, ranging from 0.1 nM to 50 μM. We then used in vitro enzymatic assays combined with computer modeling to confirm the activity of those against the viral protease and RNA polymerase. In addition, several herbal medicines were found active in the cell-based infection assay. To further evaluate the efficacy of these promising compounds in animal models, we developed a challenge assay with hamsters and found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens , and Mentha haplocalyx were effective against SARS-CoV-2 infection.
A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease, PLOS ONE, doi:10.1371/journal.pone.0245962 ,
Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of ~6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found ~50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 ≤ 50 μM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir. This work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than boceprevir and suitable for rapid repurposing.
Kinetic Characterization and Inhibitor Screening for the Proteases Leading to Identification of Drugs against SARS-CoV-2, Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.02577-20 ,
Coronavirus (CoV) disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed many lives worldwide and is still spreading since December 2019. The 3C-like protease (3CL pro ) and papain-like protease (PL pro ) are essential for maturation of viral polyproteins in SARS-CoV-2 life cycle and thus regarded as key drug targets for the disease.
A Tale of Two Proteases: MPro and TMPRSS2 as Targets for COVID-19 Therapies, Pharmaceuticals, doi:10.3390/ph16060834 ,
Considering the importance of the 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in the coronavirus disease 2019 (COVID-19) pandemic, an overview of two proteases that play an important role in the infection by SARS-CoV-2, the main protease of SARS-CoV-2 (MPro) and the host transmembrane protease serine 2 (TMPRSS2), is presented in this review. After summarising the viral replication cycle to identify the relevance of these proteases, the therapeutic agents already approved are presented. Then, this review discusses some of the most recently reported inhibitors first for the viral MPro and next for the host TMPRSS2 explaining the mechanism of action of each protease. Afterward, some computational approaches to design novel MPro and TMPRSS2 inhibitors are presented, also describing the corresponding crystallographic structures reported so far. Finally, a brief discussion on a few reports found some dual-action inhibitors for both proteases is given. This review provides an overview of two proteases of different origins (viral and human host) that have become important targets for the development of antiviral agents to treat COVID-19.
The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022, European Journal of Medicinal Chemistry, doi:10.1016/j.ejmech.2023.115491 ,
Repurposing Drugs for the Treatment of COVID-19 and Its Cardiovascular Manifestations, Circulation Research, doi:10.1161/circresaha.122.321879 ,
COVID-19 is an infectious disease caused by SARS-CoV-2 leading to the ongoing global pandemic. Infected patients developed a range of respiratory symptoms, including respiratory failure, as well as other extrapulmonary complications. Multiple comorbidities, including hypertension, diabetes, cardiovascular diseases, and chronic kidney diseases, are associated with the severity and increased mortality of COVID-19. SARS-CoV-2 infection also causes a range of cardiovascular complications, including myocarditis, myocardial injury, heart failure, arrhythmias, acute coronary syndrome, and venous thromboembolism. Although a variety of methods have been developed and many clinical trials have been launched for drug repositioning for COVID-19, treatments that consider cardiovascular manifestations and cardiovascular disease comorbidities specifically are limited. In this review, we summarize recent advances in drug repositioning for COVID-19, including experimental drug repositioning, high-throughput drug screening, omics data-based, and network medicine-based computational drug repositioning, with particular attention on those drug treatments that consider cardiovascular manifestations of COVID-19. We discuss prospective opportunities and potential methods for repurposing drugs to treat cardiovascular complications of COVID-19.
Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2, MedComm, doi:10.1002/mco2.254 ,
COVID-19 therapeutics: Small-molecule drug development targeting SARS-CoV-2 main protease, Drug Discovery Today, doi:10.1016/j.drudis.2023.103579 ,
Polyphenols as alternative treatments of COVID-19, Computational and Structural Biotechnology Journal, doi:10.1016/j.csbj.2021.09.022 ,
Enhanced compound-protein binding affinity prediction by representing protein multimodal information via a coevolutionary strategy, Briefings in Bioinformatics, doi:10.1093/bib/bbac628 ,
Abstract Due to the lack of a method to efficiently represent the multimodal information of a protein, including its structure and sequence information, predicting compound-protein binding affinity (CPA) still suffers from low accuracy when applying machine-learning methods. To overcome this limitation, in a novel end-to-end architecture (named FeatNN), we develop a coevolutionary strategy to jointly represent the structure and sequence features of proteins and ultimately optimize the mathematical models for predicting CPA. Furthermore, from the perspective of data-driven approach, we proposed a rational method that can utilize both high- and low-quality databases to optimize the accuracy and generalization ability of FeatNN in CPA prediction tasks. Notably, we visually interpret the feature interaction process between sequence and structure in the rationally designed architecture. As a result, FeatNN considerably outperforms the state-of-the-art (SOTA) baseline in virtual drug evaluation tasks, indicating the feasibility of this approach for practical use. FeatNN provides an outstanding method for higher CPA prediction accuracy and better generalization ability by efficiently representing multimodal information of proteins via a coevolutionary strategy.
Repurposing of drugs for combined treatment of COVID-19 cytokine storm using machine learning, Medicine in Drug Discovery, doi:10.1016/j.medidd.2022.100148 ,
Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2, Computational and Structural Biotechnology Journal, doi:10.1016/j.csbj.2020.08.016 ,
Artificial intelligence approach fighting COVID-19 with repurposing drugs, Biomedical Journal, doi:10.1016/j.bj.2020.05.001 ,
Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents, Communications Biology, doi:10.1038/s42003-020-01577-x ,
AbstractEmerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.
Potential inhibitors of SARS-CoV-2: recent advances, Journal of Drug Targeting, doi:10.1080/1061186X.2020.1853736 ,
Virtual Screening of Substances Used in the Treatment of SARS-CoV-2 Infection and Analysis of Compounds With Known Action on Structurally Similar Proteins From Other Viruses, Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113432 ,
Insights from a computational analysis of the SARS‐CoV‐2 Omicron variant: Host–pathogen interaction, pathogenicity, and possible drug therapeutics, Immunity, Inflammation and Disease, doi:10.1002/iid3.639 ,
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