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Riboprine for COVID-19

Riboprine has been reported as potentially beneficial for COVID-19 in the following studies. We have not reviewed riboprine in detail.
COVID-19 involves the interplay of over 200 viral and host proteins and factors providing many therapeutic targets. Scientists have proposed over 10,000 potential treatments. c19early.org analyzes 170+ treatments.
Alici, H., Structure-Based Design and In-Silico Evaluation of Computationally Proposed Curcumin Derivatives as Potential Inhibitors of the Coronaviral PLpro Enzymes, Pharmaceuticals, doi:10.3390/ph18060798
Background/Objectives: Highly pathogenic coronaviruses (CoVs), including SARS-CoV, MERS-CoV, and SARS-CoV-2, continue to pose a significant threat to global public health. Therefore, this situation highlights the urgent need for effective broad-spectrum antiviral agents. Curcumin, a naturally occurring polyphenol known for its antiviral and anti-inflammatory properties, faces limitations such as poor bioavailability and rapid metabolic degradation, restricting its practical therapeutic application. Methods: To address these limitations, this study introduces a novel design strategy aimed at 42 new curcumin derivatives with improved pharmacokinetic profiles, specifically targeting the conserved coronavirus enzyme papain-like protease (PLpro). A comprehensive in silico evaluation was performed, including ADMET (Absorption, Distribution, Metabolism, Elimination, and Toxicity) analysis, molecular docking, molecular dynamics (MD) simulations, and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) calculations. Results: Extensive pharmacokinetic and toxicological assessments (ADMET analyses) identified 19 derivatives exhibiting optimal drug-like characteristics according to Lipinski’s Rule of Five (Ro5). Molecular docking analyses demonstrated that these novel derivatives possess significantly enhanced binding affinities to PLpro enzymes from SARS-CoV, MERS-CoV, and SARS-CoV-2 compared to standard antiviral agents and natural curcumin. Further validation through MD simulations and MM/PBSA calculations confirmed the structural stability and robust interactions of the most promising derivatives within the SARS-CoV PLpro active site. Conclusions: The results of this study provide essential structural and functional insights, reinforcing the potential of these newly developed curcumin derivatives as potent, broad-spectrum antiviral agents effective against current and future coronavirus threats.
Yevsieieva et al., Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2, RSC Advances, doi:10.1039/d3ra06479d
The review outlines coronavirus SARS-CoV-2 morphology, life cycle, and essential proteins, focusing on a design strategy for dual-acting inhibitors for PLpro and Mpro proteases.
Rabie et al., Evaluation of a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: A repurposing research study, Medicinal Chemistry Research, doi:10.1007/s00044-022-02970-3
AbstractMysterious evolution of a new strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the Omicron variant, led to a new challenge in the persistent coronavirus disease 2019 (COVID-19) battle. Objecting the conserved SARS-CoV-2 enzymes RNA-dependent RNA polymerase (RdRp) and 3′-to-5′ exoribonuclease (ExoN) together using one ligand is a successful new tactic to stop SARS-CoV-2 multiplication and COVID-19 progression. The current comprehensive study investigated most nucleoside analogs (NAs) libraries, searching for the most ideal drug candidates expectedly able to act through this double tactic. Gradual computational filtration afforded six different promising NAs, riboprine/forodesine/tecadenoson/nelarabine/vidarabine/maribavir. Further biological assessment proved that riboprine and forodesine are able to powerfully inhibit the replication of the new virulent strains of SARS-CoV-2 with extremely minute in vitro anti-RdRp and anti-SARS-CoV-2 EC50 values of about 0.21 and 0.45 μM for riboprine and about 0.23 and 0.70 μM for forodesine, respectively, surpassing both remdesivir and the new anti-COVID-19 drug molnupiravir. These biochemical findings were supported by the prior in silico data. Additionally, the ideal pharmacophoric features of riboprine and forodesine molecules render them typical dual-action inhibitors of SARS-CoV-2 replication and proofreading. These findings suggest that riboprine and forodesine could serve as prospective lead compounds against COVID-19.
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
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