Low Binding Research Articles

Subtle Structural Changes across the Boundary between A2AR/A2BR Dual Antagonism and A2BR Antagonism: A Novel Class of 2-Aminopyrimidine-Based Derivatives.

Aberrantly elevated adenosine in the tumor microenvironment exerts its immunosuppressive functions through adenosine receptors A2AR and A2BR. Antagonism of A2AR and A2BR has the potential to suppress tumor growth. Herein, we report a systemic assessment of the effects of an indole modification at position 4, 5, 6, or 7 on both A2AR/A2BR activity and selectivity of novel 2-aminopyrimidine compounds. Substituting indole at the 4-/5-position produced potent A2AR/A2BR dual antagonism, whereas the 6-position of indole substitution gave highly selective A2BR antagonism. Molecular dynamics simulation showed that the 5-cyano compound 7ai had a lower binding free energy than the 6-cyano compound 7aj due to water-bridged hydrogen bond interactions with E169 or F168 in A2AR. Of note, dual A2AR/A2BR antagonism by compound 7ai can profoundly promote the activation and cytotoxic function of T cells. This work provided a strategy for obtaining novel dual A2AR/A2BR or A2BR antagonists by fine-tuning structural modification.

Coating of ThO2 (111) surface with two–dimensional sheets for potential corrosion protection

ThO2 is an important nuclear fuel that could be used in molten salt reactors, and its corrosion behaviors and anticorrosion mechanisms should be in–depth understood. More emerging two–dimensional (2D) sheets show potentially great corrosion resistance in metal corrosion due to their barrier properties and poor conductivity. In this work, first-principle calculations were performed to assess the potential ability of a series of 2D sheets for the corrosion protection of nuclear material ThO2. The strong binding interaction is found for two MXenes (Mo2C and Ti3C2 sheets) with ThO2 (111) surface revealed by their fairly low binding energy. The high binding strength of Mo2C and Ti3C2 sheets with ThO2 (111) surface originates from the remarkable charge redistribution around the interfaces. The coatings of the semiconducting 2D sheets on the ThO2 surface weaken the interaction with H2O. The one–side passivated MXenes can be efficiently anchored on the ThO2 surface through metal side, and the passivated side shows low adsorption affinity to H2O molecule. Our current work provides the basic understanding of the interaction between 2D nanosheets and ThO2 surfaces.

Identification of Potent Acetylcholinesterase Inhibitors as New Candidates for Alzheimer Disease via Virtual Screening, Molecular Docking, Dynamic Simulation, and Molecular Mechanics-Poisson-Boltzmann Surface Area Calculations.

Huperzine A (HUP) plays a crucial role in Alzheimer's therapy by enhancing cognitive function through increased cholinergic activity as a reversible acetylcholinesterase (AChE) inhibitor. Despite some limitations being seen in AChE inhibitors, ongoing research remains dedicated to finding innovative and more effective treatments for Alzheimer's disease. To achieve the goal of the discovery of potential HUP analogues with improved physicochemical properties, less toxic properties, and high biological activity, many in silico methods were applied. Based on the acetylcholinesterase-ligand complex, an e-pharmacophore model was developed. Subsequently, a virtual screening involving a collection of 1762 natural compounds, sourced from the PubChem database, was performed. This screening yielded 131 compounds that exhibited compatibility with the established pharmacophoric hypothesis. These selected ligands were then subjected to molecular docking within the active site of the 4EY5 receptor. As a result, we identified four compounds that displayed remarkable docking scores and exhibited low free binding energy to the target. These top four compounds, CID_162895946, CID_44461278, CID_44285285, and CID_81108419, were submitted to ADMET prediction and molecular dynamic simulations, yielding encouraging findings in terms of their pharmacokinetic characteristics and stability. Finally, the molecular dynamic simulation, cross-dynamic correlation matrix, free energy landscape, and MM-PBSA calculations demonstrated that two ligands from the selected ligands formed very resilient complexes with the enzyme acetylcholinesterase, with significant binding affinity. Therefore, these two compounds are recommended for further experimental research as possible (AChE) inhibitors.

Modulating Inorganic Dimensionality of Ultrastable Lead Halide Coordination Polymers for Photocatalytic CO2 Reduction to Ethanol.

Lead halide hybrids have shown great potentials in CO2 photoreduction, but challenging to afford C2+ reduced products, especially using H2O as the reductant. This is largely due to the trade-off problem between instability of the benchmark 3D structures and low carrier mobility of quasi-2D analogues. Herein, the lead halide dimensionality of robust coordination polymers (CP) was modulated by organic ligands differing in a single-atom change (NH vs. CH2), in which the NH groups coordinate with interlamellar [PbI2] clusters to achieve the important 2D→3D transition. This first CP based on 3D cationic lead iodide sublattice possesses both high aqueous stability and a low exciton binding energy of 25 meV that is on the level of ambient thermal energy, achieving artificial photosynthesis of C2H5OH. Photophysical studies combined with theoretical calculations suggest the bridging [PbI2] clusters in the 3D structure not only results in enhanced carrier transport, but also promotes the intrinsic charge polarization to facilitate the C-C coupling. With trace loading of Rh cocatalyst, the apparent quantum efficiency of the 3D CP reaches 1.4 % at 400 nm with a high C2H5OH selectivity of 89.4 % (product basis), which presents one of the best photocatalysts for C2 products to date.

Modulating Inorganic Dimensionality of Ultrastable Lead Halide Coordination Polymers for Photocatalytic CO2 Reduction to Ethanol

AbstractLead halide hybrids have shown great potentials in CO2 photoreduction, but challenging to afford C2+ reduced products, especially using H2O as the reductant. This is largely due to the trade‐off problem between instability of the benchmark 3D structures and low carrier mobility of quasi‐2D analogues. Herein, the lead halide dimensionality of robust coordination polymers (CP) was modulated by organic ligands differing in a single‐atom change (NH vs. CH2), in which the NH groups coordinate with interlamellar [PbI2] clusters to achieve the important 2D→3D transition. This first CP based on 3D cationic lead iodide sublattice possesses both high aqueous stability and a low exciton binding energy of 25 meV that is on the level of ambient thermal energy, achieving artificial photosynthesis of C2H5OH. Photophysical studies combined with theoretical calculations suggest the bridging [PbI2] clusters in the 3D structure not only results in enhanced carrier transport, but also promotes the intrinsic charge polarization to facilitate the C−C coupling. With trace loading of Rh cocatalyst, the apparent quantum efficiency of the 3D CP reaches 1.4 % at 400 nm with a high C2H5OH selectivity of 89.4 % (product basis), which presents one of the best photocatalysts for C2 products to date.

The influence of selenophene π-linker on photovoltaic properties of pyrrole-4,6(5-H)-dione-based chromophores: A quantum chemical study

A series of 4-H-selenopheno[3,4-c]pyrrole-4,6(5-H)-dione based chromophores (DMSD1-DMSD7) was designed via the introduction of selenophene units (n = 2–7) in the π–spacer of reference compound (DMSR) owing to growing demand of non-fullerene based organic solar cells. The influence of selenophene π–spacer on photovoltaic properties of entitled molecules was explored by utilizing CAM-B3LYP/6-311G (d,p) functional. All the designed compounds were found with lesser values of energy gaps (4.342–3.904 eV) as compared to DMSR (4.764 eV). Similarly, their absorption values were found in the visible region (523.560–533.403 nm) in dichloromethane solvent. Moreover, the entitled chromophores exhibited lower binding energies (1.895–1.566 eV) with higher open circuit voltage values which supported their excellent charge transference properties. The unique properties like least value of bandgap (3.904 eV) with greater charge transfer phenomena were examined for DMSD7 due to the presence of most elongated chain of selenophene-based π–spacer. The density of state and transition density matrix maps illustration further confirmed the efficient charge transfer in DMSD7. Overall, these findings disclosed that by utilizing selenophene π–spacer, photovoltaic properties of organic materials can be efficiently improved.

Efficient ethanol production from masson pine sawdust by various organosolv pretreatment and modified pre-hydrolysis simultaneous saccharification and fermentation

Pretreatment is a key step in lignocellulosic biorefinery. In this study, the combination of organosolv pretreatment and lignin repolymerization inhibitor was put forward to fractionate the lignocellulosic biomass, providing readily hydrolyzed substrate. Results showed that, acidic 1,4-butanediol pretreatment extensively removed lignin from softwood, reducing the physical blockage effect of lignin. Besides, lignin repolymerization inhibitors were employed to modify lignin, giving rise to lower unproductive binding effect of lignin. As a result, maximum 79.9 ± 0.3 % of original lignin in raw biomass could be removed, and 97.9 ± 0.5 % of glucan in pretreated solid could be converted into fermentable sugars after acidic butanediol pretreatment assisted by sodium 2-naphthol-7-sulphonate and enzymatic hydrolysis at 2 % glucan loading. Furthermore, a modified pre-hysrolysis simultaneous saccharification and fermentation process at 10 % glucan loading produced 45.6 ± 1.7 g/L ethanol, with ethanol yield of 18.7 ± 0.4 g/100 g raw biomass. Finally, the mass balance revealed that the lignocellulosic biorefinery based on acidic butanediol pretreatment assisted by sodium 2-naphthol-7-sulphonate could achieve full utilization of lignocellulosic components to co-produce ethanol, lignin materials and hemicellulose-derived mono-saccharides.

Unveiling the Broad Substrate Specificity of Deoxynivalenol Oxidation Enzyme DepA and Its Role in Detoxifying Trichothecene Mycotoxins.

DepA, a pyrroloquinoline quinone (PQQ)-dependent enzyme isolated from Devosia mutans 17-2-E-8, exhibits versatility in oxidizing deoxynivalenol (DON) and its derivatives. This study explored DepA's substrate specificity and enzyme kinetics, focusing on DON and 15-acetyl-DON. Besides efficiently oxidizing DON, DepA also transforms 15-acetyl-DON into 15-acetyl-3-keto-DON, as identified via LC-MS/MS and NMR analysis. The kinetic parameters, including the maximum reaction rate, turnover number, and catalytic efficiency, were thoroughly evaluated. DepA-PQQ complex docking was deployed to rationalize the substrate specificity of DepA. This study further delves into the reduced toxicity of the transformation products, as demonstrated via enzyme homology modeling and in silico docking analysis with yeast 80S ribosomes, indicating a potential decrease in toxicity due to lower binding affinity. Utilizing the response surface methodology and central composite rotational design, mathematical models were developed to elucidate the relationship between the enzyme and cofactor concentrations, guiding the future development of detoxification systems for liquid feeds and grain processing. This comprehensive analysis underscores DepA's potential for use in mycotoxin detoxification, offering insights for future applications.

Endogenous EWSR1 Exists in Two Visual Modalities That Reflect Its Associations with Nucleic Acids and Concentration at Sites of Active Transcription.

EWSR1 is a member of the FET family of nucleic acid binding proteins that includes FUS and TAF15. Here, we report the systematic analysis of endogenous EWSR1's cellular organization in human cells. We demonstrate that EWSR1, which contains low complexity and nucleic acid binding domains, is present in cells in faster and slower-recovering fractions, indicative of a protein undergoing both rapid exchange and longer-term interactions. The employment of complementary high-resolution imaging approaches shows EWSR1 exists in two visual modalities, a distributed state which is present throughout the nucleoplasm, and a concentrated state consistent with the formation of foci. Both EWSR1 visual modalities localize with nascent RNA. EWSR1 foci concentrate in regions of euchromatin, adjacent to protein markers of transcriptional activation, and significantly colocalize with phosphorylated RNA polymerase II. Our results contribute to bridging the gap between our understanding of the biophysical and biochemical properties of FET proteins, including EWSR1, their functions as transcriptional regulators, and the participation of these proteins in tumorigenesis and neurodegenerative disease.

Bromine Atoms Decorated Pyene-based Covalent Organic Frameworks for Accelerated Photocatalytic H2 Production.

Designing materials with low exciton binding energy is an efficient way of improving the hydrogen production performance of COFs（Covalent Organic Frameworks. Here, it is demonstrated that the strategy of decorating bromine atoms on Pyene-based COFs can achieve elevated photocatalytic H2 evolution rates (HER = 13.61mmol g-1h-1). Low-temperature fluorescence and time-resolved fluorescence spectroscopy (TRPL) indicate that the introduction of bromine atoms can significantly suppress charge recombination. DFT (Density Functional Theory) calculation clarified that the C atoms adjacent to Br are the active sites with a reduced energy barrier in the process of formatting H intermediate species (H*). The modification strategy of Br atoms in COF furnishes a new medium for exploiting exquisite photocatalysts.

Investigating the potential of lead-free Cs2AgBiI6 and Cs2AgBiBr6 double perovskites for photovoltaic applications

In the immediate past, there lies a pivotal relevance in lead-free A2B+B3+X6 halide double perovskites (HDPs), which have gained prominence as environmentally sustainable photovoltaic materials due to their favorable features such as small carrier effective masses, suitable bandgaps and low exciton binding energies. In this work, the photovoltaic performance of the environmentally friendly Cs2AgBiI6 and Cs2AgBiBr6 are assessed through the utilization of 1D Solar Cell Capacitance Simulator (SCAPS-1D) software. Various physical parameters such as defect density, electron affinity, and doping concentration are systematically investigated along with effect of thickness, operating temperature, and metal back work function, in the pursuit of optimal device performance in terms of power conversion efficiency (PCE). The simulation findings suggest that the optimal band structure of PSCs aids in the separation and transport of carriers. The device efficiency of both PSCs exhibited an improvement as the shunt resistance was increased, whereas it experienced a decline as the series resistance and operating temperature were increased. The determined PCE (%) from optimized Cs2AgBiI6 and Cs2AgBiBr6 perovskite solar cells (PSCs) are 24.11 and 18.71%, respectively. Theoretical implications of these results will be of great significance in the design and advancement of stable and efficient HDPs.

In silico Molecular Docking Approach to Identify Potential Antihypertensive Compounds from Ajuga integrifolia Buch.-Ham. Ex D. Don (Armagusa).

Ajuga integrifolia (Armagusa) is used as a decoction to treat high blood pressure and diabetes, widely in Ethiopia. Specific compounds for anti-hypertension activity were not identified so far. This study aims to provide a scientific basis for the therapeutic use of A. integrifolia as an antihypertension agent. In silico studies were used to evaluate the antihypertensive components of A. integrifolia. Flavonoids identified using HPLC analysis and iridoid glycosides isolated from A. integrifolia in this study and those isolated from synonyms (A. remota and A. bractosa) were considered in the molecular docking study. Interactions were studied by using Autodock vina (1.2) on PyRx 0.8 and visualizing in 2D and 3D using ligPlot+ and Discovery studio software. Activities like vasoprotection and druglikeness properties were predicted using online servers. Flavonoids such as quercetin, myricetin, and rutin were identified and quantified by HPLC analysis from different extracts of A. integrifolia. Reptoside and 8-O-acetylharpgide isolated from the aerial part of A. integrifolia. The binding energies of all 17 candidates considered in this study range from -10.2 kcal/mol to -7.5 kcal/mol and are lower than enalapril (reference drug: -5.9 kcal/mol). The binding energies, in most case, constitute hydrogen bonding. Biological activity predicted using PASS test also showed that the flavonoids have more probability of activity than the iridoid glycosides. Druglikeness properties of the candidate molecules showed that most follow the Lipinski rule of five with few violations. Lower binding energies involving hydrogen bonding and predicted activities concerning hypertension confirm the traditional use of the aerial part of the medicinal plant concerned. Flavonoids: rutin, myricetin, quercetin, and kaempferol take the leading role in the antihypertensive activity of the aerial part of A. integrifolia. The iridoid glycosides studied are almost similar in their effect on their antihypertensive activity and still better than the reference drug.

The Role of Bromelain and Papain Proteolytic Potential Binding to Crystalline P23T Γd Protein in Congenital Cataracts

Background: Congenital cataracts can cause permanent vision loss. The etiology of congenital cataracts varies widely. The exact etiology can’t be identified, but usually there an autosomal dominant inheritance. Objective: To assess the proteolytic potential of Bromelain and Papain enzymes against Crystalline P23T γD. Methods: This study is a pre-experimental study with a computer-based one shot case study approach. Papain enzyme data using 9PAP code and bromelain enzyme data using 1BI6 were obtained from the National Center of Biotechnology Information database (NCBI: www.ncbi.nlm.nih.gov/). Assessment of the proteolytic potential of Bromelain and Papain enzymes against Crystalline P23T D data using 2KFB code cluspro www.cluspro.bu.edu/home.php and data analysis. Results: The binding affinity of bromelain is -735.1 KCal/Mol and papain is -730.4 KCal/Mol. Conclusion: The bromelain enzyme has a lower binding affinity value than the papain enzyme, so it has the ability to form stable bond to the crystalline P23T D protein better than papain enzyme.

Identifying TMPRSS2 Inhibitors by Drug Repurposing Screenings of Known fXIa Inhibitors: A Computational Study

Background: SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Hence the inhibition of TMPRSS2 may block or decrease the severity of SARSCoV- 2, making TMPRSS2 an attractive target for COVID-19. fXIa has a similar binding pocket as TMPRSS2, implying the possibility of fXIa inhibitors being TMPRSS2 inhibitors. Methods: In order to find potential TMPRSS2 inhibitors, molecular docking of known fXIa inhibitors was performed. Molecular dynamics simulations and MM/GBSA were conducted on representative compounds with characteristic binding modes. R-group enumeration was used to generate compounds with better binding interactions. Results: Three scaffolds can make hydrogen bonds with Gly439 and Ser441, and form the chloride– Tyr474 interactions at S1 pocket as well. Further structure optimization of one scaffold found that two compounds have better docking scores and lower binding free energies. Conclusion: Compounds R1a and R1b can be taken as potentially reversible inhibitors of TMPRSS2. Our results could provide insight into both the discovery and lead optimization of TMPRSS2 inhibitors.

Phytochemistry and Biological Assessment of Thuja articulata Trunk Barks: HPLC-PDA-ESI-MS Analysis, Bioevaluation, and Molecular Docking

Background: Thuja articulata is a Mediterranean forest species from the Cupressaceae family, it has been used in popular medicine to treat several diseases. Various studies have been carried out in vitro using diverse T. articulata extracts to understand its traditional use. Methods: In this study, the ethyl acetate extract of T. articulata trunk barks was chemically identified using HPLC-PDA-ESI-MS, then examined in vitro for its antioxidant and α-amylase inhibitory effects. A molecular docking study was also performed to reinforce the noted bioactivities. Results: HPLC-PDA-ESI-MS analysis led to the identification of 22 polyphenolic compounds in the ethyl acetate extract of T. articulata trunk barks. This extract revealed interesting in vitro antioxidant properties and a significant α-amylase inhibitory action (IC50 = 16.08 ± 1.27 μg/mL). In silico analysis was found to agree with the in vitro studies in which major constituents of the ethyl acetate extract revealed low binding energy and a correct mode of interaction in the active pocket of the enzyme (PDB: 7TAA). The anti-a-amylase potential could be due either to a synergistic or individual action of certain constituents present in this extract. Conclusion: This study illustrates that the ethyl acetate extract of T. articulata trunk barks has potent sources of antioxidants and α-amylase inhibitors to be explored.

Low Viscosity Ionic Liquids as Novel Dopants in Poly (Methyl Methacrylate) Polymer Electrolyte: Detailed Photoelectrochemical Studies

Background: A propitious electrolyte for supercapacitors, solid polymer electrolytes (SPEs) has been used because of their flexibility and highly conducting good electrode-electrolyte interface. Poly (methyl methacrylate) (PMMA)-based SPEs have acknowledged extensive interest due to their integrity in synthesis, good mechanical stability, low binding energy, low mass density with ionic salts, and magnificent charge carrier mobility. Interesting ionic liquids show their novelty towards conductivity enhancement and suppressing crystallinity i.e. acts as a plasticizer as well as an ionic source. Due to these advantageous properties, ionic liquids (ILs) seem to be a good player in developing highly efficient electrochemical devices. Method: To overcome the low ionic conductivity (σ) and poor mechanical stability. ILs assume to be novel candidates. This review is toward defining the role of ILs as plasticizers, not as a solvent. Result: Due to the widespread applicability of these ILs, we focus our review on taking a common example of polyether i.e. PMMA using the solution cast method. Electrical and electrochemical are also discussed in detail. Conclusion: On the the basis of electrical and photoelectrochemical performance reported in this article, we can assure the scientific community that ILs can act as a potential candidate like a plasticizer for highly efficient electrochemical devices.

Radiosynthesis and In Vitro Evaluation of [11C]tozadenant as Adenosine A2A Receptor Radioligand.

Tozadenant (4-hydroxy-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A2A receptor (A2AR) antagonist and a promising lead structure for the development of A2AR-selective positron emission tomography (PET) probes. Although several 18F-labelled tozadenant derivatives showed favorable in vitro properties, recent in vivo PET studies observed poor brain penetration and lower specific binding than anticipated from the in vitro data. While these findings might be attributable to the structural modification associated with 18F-labelling, they could also reflect inherent properties of the parent compound. However, PET studies with radioisotopologues of tozadenant to evaluate its cerebral pharmacokinetics and brain distribution are still lacking. In the present work, we applied N-Boc-O-desmethyltozadenant as a suitable precursor for the preparation of [O-methyl-11C]tozadenant ([11C]tozadenant) by O-methylation with [11C]methyl iodide followed by acidic deprotection. This approach afforded [11C]tozadenant in radiochemical yields of 18 ± 2%, with molar activities of 50-60 GBq/µmol (1300-1600 mCi/µmol) and radiochemical purities of 95 ± 3%. In addition, in vitro autoradiography in pig and rat brain slices demonstrated the expected striatal accumulation pattern and confirmed the A2AR specificity of the radioligand, making it a promising tool for in vivo PET studies on the cerebral pharmacokinetics and brain distribution of tozadenant.

Physiological Functions of the Cello-Oligosaccharides Binding CebE in the Pathogenic Streptomyces sp. AMCC400023.

Potato common scab, an economically important disease worldwide, is caused by pathogenic Streptomyces strains mainly through the effects of thaxtomin. The cello-oligosaccharides binding protein CebE is proposed as a gateway to the pathogenic development of Streptomyces scabiei. In this study, two functional CebE encoding genes, GEO5601 and GEO7671, were identified in pathogenic Streptomyces sp. AMCC400023. With a higher binding affinity towards signal molecules, the deletion of GEO5601 severely impaired thaxtomin-producing capacity and reduced the strain's pathogenicity. Transcriptional analysis confirmed that CebE5601 is also responsible for the import and provision of carbon sources for cell growth. With lower binding affinity, the pathogenicity island (PAI)-localized CebE7671 may assume a new function of mediating the biological process of sporulation, given the significantly impaired formation of ΔGEO7671 spores. The mechanisms of action of CebE proteins unraveled in Streptomyces sp. AMCC400023 will help pave the way for more effective prevention of the potato common scab disease.

Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer

NF-κB pathway is involved in inflammation; however, recent data shows its role also in cancer development and progression, including metastasis. To understand the role of NF-κB interactome dynamics in cancer, we study the complexity of breast cancer interactome in luminal A breast cancer model and its rearrangement associated with NF-κB modulation. Liquid chromatography-mass spectrometry measurement of 160 size-exclusion chromatography fractions identifies 5460 protein groups. Seven thousand five hundred sixty eight interactions among these proteins have been reconstructed by PrInCE algorithm, of which 2564 have been validated in independent datasets. NF-κB modulation leads to rearrangement of protein complexes involved in NF-κB signaling and immune response, cell cycle regulation, and DNA replication. Central NF-κB transcription regulator RELA co-elutes with interactors of NF-κB activator PRMT5, and these complexes are confirmed by AlphaPulldown prediction. A complementary immunoprecipitation experiment recapitulates RELA interactions with other NF-κB factors, associating NF-κB inhibition with lower binding of NF-κB activators to RELA. This study describes a network of pro-tumorigenic protein interactions and their rearrangement upon NF-κB inhibition with potential therapeutic implications in tumors with high NF-κB activity.

PHYSICOCHEMICAL AND PHARMACOKINETIC ANALYSIS AND DOCKING OF DRUG REPOSITIONING AGAINST SARS-COV-2: AN IN SILICO STUDY

Studies on the development of effective and cost-effective oral drugs are the new priority of the pharmaceutical industry for the prevention and treatment of COVID-19. This work was based on the computational analysis of physicochemical parameters, pharmacokinetic and toxicological measurements, molecular docking and in silico measurement of the antiviral activity of 12 repositionable drugs. The Molinspiration platform (physical-chemical parameters), pkCSM® (absorption, distribution, metabolism and excretion), OSIRIS Property Explorer® (toxicological measurements), Seam® (Docking with the RdRp protein) and AVCpred server® (antiviral activity) were used. Considering the 12 selected repositionable drugs, molecular anchoring data with the RdRp protein, only the drug tilorone had lower binding energy than the control used in this study (Molnupiravir). Ledipasvir, daclatasvir and piperaquine showed the best percentage of antiviral inhibition considering the control pattern. ADMETox data showed that piperaquine has a high toxicological potential for mutagenesis, tumorigenesis and irritant effects. The findings of this study indicate that ledipasvir and daclatasvir showed greatest potential for inhibition RdRp and action against COVID-19.