GC-14 for COVID-19

 GC-14 has been reported as potentially beneficial for COVID-19 in the following studies.
COVID-19 involves the interplay of 350+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 10,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed GC-14 in detail.
Fassi et al., Support Vector Machine Identification of Small Molecule Binders to an Understudied Allosteric Site of SARS‐CoV‐2 Mpro for Next‐Generation PROTAC‐Based Therapeutics, Archiv der Pharmazie, doi:10.1002/ardp.70169
ABSTRACT The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has underscored the urgent need for novel antiviral strategies. One of the primary targets of interest is the SARS‐CoV‐2 main protease (Mpro), which plays a crucial role in viral replication. Building on our prior work involving machine learning (ML)‐based virtual screening for potential Mpro inhibitors, we sought to experimentally validate top‐ranked candidates. Microscale thermophoresis (MST) was used to assess the binding affinity, leading to the identification of three promising hits from a library of 180 compounds. Notably, one compound demonstrated high‐affinity binding to SARS‐CoV‐2 Mpro ( K d = 2.8 ± 0.9 µM). However, enzymatic assays revealed that none of the hit compounds inhibited the activity of the protease, suggesting a non‐competitive binding. Docking and molecular dynamics (MD) simulations allowed to identify an accessory site in which the compounds exhibited stable interactions. These findings suggest that the identified compounds may serve as a starting point for the rational design of degradation‐inducing strategies, such as proteolysis‐targeting chimeras (PROTACs), targeting SARS‐CoV‐2 Mpro, and highlight the value of integrating ML‐driven discovery with biophysical and computational validation in antiviral drug development.
Delgado et al., SARS-CoV-2 Mpro inhibitor identification using a cellular gain-of-signal assay for high-throughput screening, SLAS Discovery, doi:10.1016/j.slasd.2024.100181
Yang et al., Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (Mpro), ACS Omega, doi:10.1021/acsomega.4c03023
Citarella et al., Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives, Biomolecules, doi:10.3390/biom13091339
The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.
Carabineiro et al., CuFe2O4 Magnetic Nanoparticles as Heterogeneous Catalysts for Synthesis of Dihydropyrimidinones as Inhibitors of SARS-CoV-2 Surface Proteins—Insights from Molecular Docking Studies, Processes, doi:10.3390/pr11082294
In this study, we present the highly efficient and rapid synthesis of substituted dihydropyrimidinone derivatives through an ultrasound-accelerated approach. We utilize copper ferrite (CuFe2O4) magnetic nanoparticles as heterogeneous catalysts, employing the well-known Biginelli reaction, under solvent-free conditions. The impact of the solvent, catalyst amount, and catalyst type on the reaction performance is thoroughly investigated. Our method offers several notable advantages, including facile catalyst separation, catalyst reusability for up to three cycles with the minimal loss of activity, a straightforward procedure, mild reaction conditions, and impressive yields, ranging from 79% to 95%, within short reaction times of 20 to 40 min. Furthermore, in the context of fighting COVID-19, we explore the potential of substituted dihydropyrimidinone derivatives as inhibitors of three crucial SARS-CoV-2 proteins. These proteins, glycoproteins, and proteases play pivotal roles in the entry, replication, and spread of the virus. Peptides and antiviral drugs targeting these proteins hold great promise in the development of effective treatments. Through theoretical molecular docking studies, we compare the binding properties of the synthesized dihydropyrimidinone derivatives with the widely used hydroxychloroquine molecule as a reference. Our findings reveal that some of the tested molecules exhibit superior binding characteristics compared to hydroxychloroquine, while others demonstrate comparable results. These results highlight the potential of our synthesized derivatives as effective inhibitors in the fight against SARS-CoV-2.