X77 for COVID-19

X77 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 12,000+ potential treatments. c19early.org analyzes 220+ treatments. We have not reviewed X77 in detail.
Barış et al., Effective Fragrance Molecules and Essential Oils: A Potential Relief for COVID-19, Natural Product Communications, doi:10.1177/1934578X261487547
Objectives Essential oils and their chemical constituents are recognized for their antimicrobial properties against many infections. In this study, some molecules of essential oils are identified as potentially effective on the MPro of SARS-CoV-2 and as a BRD2 inhibitors. These essential oils were combined in an optimum formulation as (Anti-COV19-VERS4). This study evaluates the role of Anti-COV19-VERS4, in preventing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) contagiousness and its secondary effects on infected tissues by in-vivo experiments. Methods Anti-COV19-VERS4 is formulated based on molecular docking studies. Following cytotoxic and antiviral dose determination, SARS-CoV-2 infected transgenic mice were treated with Anti-COV19-VERS4 spray. RT-qPCR was used to detect viral load and histopathologic analysis was performed. The experiment was terminated on the days of 5 and 6 when SARS-CoV-2 infection peaked. RT-qPCR was used to detect viral load and histopathologic analysis was performed. Two-way ANOVA and Student’s t -tests were used for statistical analysis. Results Cytotoxicity and neutralization assays revealed that the most effective dilution of Anti-COV19-VERS4 showing cytopathic effect (CPE) was 1/2600 and the 24-hour CC50 dose was 0.0154 mg/L. During in-vivo trials, 3 out of 14 mice in the control group died due to infection. The virus load of the Anti-COV19-VERS4 spray group on day 6 decreased compared to the control group. Moreover, lung injury scores for the Anti-COV19-VERS4 spray group were significantly lower than the control group on the 6 th day (p<0.05). This study demonstrates that Anti-COV19-VERS4 may be useful for preventing the contagiousness of SARS-CoV-2 and relieving lung injury. Conclusion Anti-COV19-VERS4 may be helpful as a cost-effective and efficacious adjunctive therapy for SARS-CoV-2.
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.
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.
Atatreh et al., Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds, Journal of Enzyme Inhibition and Medicinal Chemistry, doi:10.1080/14756366.2025.2460045
Yang et al., Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (Mpro), ACS Omega, doi:10.1021/acsomega.4c03023
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.