Rigidity and Flexibility of Pyrazole, s-Triazole, and v-Triazole Derivative of Chloroquine as Potential Therapeutic against COVID-19

Based on the core unit of chloroquine, new types of N-heterocyclic compounds that are fused together have been made. The compounds were put into two groups. In series A, the five-member hetero-rings were directly connected to the core unit, while in series B, the CH2 group was used to make the five-member ring more flexible (series B). Using the Gaussian 09 programme, the DFT method with hybrid correlation functional (B3LYP) and 6-311 (d, p) basis sets were used to figure out how to optimize and measure the quantum chemical properties of molecules. The molecular overeating environment (MOE) programme is used to study molecular docking. The binding of flexible compounds shows that AC8, AC10, AC3, and AC5 have the strongest binding affinities compared to the other candidates, while the rigid molecules ARC10 and ARC6 have the lowest binding affinities. In general, the results of the binding affinity showed that the drugs and receptors being studied might have anti-Covid-19 properties. Likewise, the flexible compounds AC8, AC10, AC3, and AC5 had the lowest Ki values of those made and could be used as a treatment. Our virtual physicochemical evaluation of all compounds in series A and B showed that all of them met the limits for molecular weight, lipophilicity (MLogP 4.15, the octanol-water partition coefficient), and water solubility. In addition to MR, the number of H-bond acceptors and the PSA were both within the acceptable range. It seems that the number of rotatable bonds is the only physicochemical property that separates the compounds in series B. The scores of compounds AC3, AC4, AC7, AC8, AC11, and AC12 are outside the acceptable range when compared to the results of chloroquine as the parent compound. © 2023 by SPC (Sami Publishing Company).

Mucormycosis: Modern diagnostics and treatment, existing problems and new trends in antifungal therapy.

Over the last decade, the introduction of new antifungal drugs and diagnostic procedures has improved the prognosis of hematological patients with invasive fungal disease (IFD), primarily invasive aspergillosis. Despite effective antifungal prophylaxis against the most common IFD caused by Aspergillus spp., rates of IFD due to rare pathogens being resistant to most antifungal drugs, including mucormycosis have been increased. The main group of patients having a high risk of mucormycosis is deeply immunocompromised patients who received chemotherapy for acute leukemia, patients undergoing allogeneic bone marrow transplantation, or treated with corticosteroids for graft-versushost disease. Currently, the urgency of this complication is significantly higher due to COVID-19 pandemic and extensive use of corticosteroids for the treatment of COVID-19. Despite the fact that the criteria for the diagnosis of IFD EORTC/MSG 2008 and 2020 have been developed and implemented into practice in most countries, mucormycosis still remains a difficult-to-diagnose IFD, where the factor of rapid diagnosis is a main factor of treatment success. Medications available for the treatment of IFD include polyenes, triazoles, and echinocandins. For a long time, the drug of choice for the treatment of mucormycosis was liposomal amphotericin B. However, a new effective drug has been approved for the treatment of both mucormycosis and IFD, caused by multiple pathogens - isavuconazole. This review presents new data on the epidemiology of mucormycosis, diagnosis approaches and current international treatment guidelines.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Synthesis, antimycobacterial screening, molecular docking, ADMET prediction and pharmacological evaluation on novel pyran-4-one bearing hydrazone, triazole and isoxazole moieties: Potential inhibitors of SARS CoV-2.

The respiratory infection tuberculosis is caused by the bacteria Mycobacterium tuberculosis and its unrelenting spread caused millions of deaths around the world. Hence, it is needed to explore potential and less toxic anti-tubercular drugs. In the present work, we report the synthesis and antitubercular activity of four different (hydrazones 7-12, O-ethynyl oximes 19-24, triazoles 25-30, and isoxazoles 31-36) hybrids. Among these hybrids 9, 10, 33, and 34, displayed high antitubercular activity at 3.12 g/mL with >90% of inhibitions. The hybrids also showed good docking energies between -6.8 and -7.8 kcal/mol. Further, most active molecules were assayed for their DNA gyrase reduction ability towards M. tuberculosis and E.coli DNA gyrase by the DNA supercoiling and ATPase gyrase assay methods. All four hybrids showed good IC50 values comparable to that of the reference drug. In addition, the targets were also predicted as a potential binder for papain-like protease (SARS CoV-2 PLpro) by molecular docking and a good interaction result was observed. Besides, all targets were predicted for their absorption, distribution, metabolism, and excretion - toxicity (ADMET) profile and found a significant amount of ADMET and bioavailability.

Post-Coronavirus Disease Mucormycosis: Predisposing Factors and Possible Treatment: A Narrative Review

Mucormycosis, commonly known as black fungus, is a life-threatening fungal infection be-longing to the order Mucorales. It affects individuals with an impaired immune response or immune disorders such as diabetes mellitus, induced immunosuppression, hematological cancers, acquired immune deficiency syndrome, or who have undergone organ transplantation. The symptoms of black fungus in-clude difficulty in breathing, blurred vision, coughing out blood, chest pain, and blackening over the area of the nose. Tissue necrosis is the main symptom of this infection. Its prevalence is increasing day by day and has been observed in vulnerable patients, including patients suffering from COVID-19 (corona-virus) and those who have been recovered. It has been observed that black fungus cases are increasing in recovered COVID patients, and various cases of white and yellow fungus are also reported. The treatment approach includes the use of antifungal agents, triazoles, surgery, combination therapy, etc. This review describes the clinical manifestation, predisposing factors, and treatment strategies of mucormycosis.Copyright © 2022 Bentham Science Publishers.

Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential.

COVID-19 infection is now considered one of the leading causes of human death. As an attempt towards the discovery of novel medications for the COVID-19 pandemic, nineteen novel compounds containing 1,2,3-triazole side chains linked to phenylpyrazolone scaffold and terminal lipophilic aryl parts with prominent substituent functionalities were designed and synthesized via a click reaction based on our previous work. The novel compounds were assessed using an in vitro effect on the growth of SARS-CoV-2 virus-infested Vero cells with different compound concentrations: 1 and 10 µM. The data revealed that most of these derivatives showed potent cellular anti-COVID-19 activity and inhibited viral replication by more than 50% with no or weak cytotoxic effect on harboring cells. In addition, in vitro assay employing the SARS-CoV-2-Main protease inhibition assay was done to test the inhibitors' ability to block the common primary protease of the SARS-CoV-2 virus as a mode of action. The obtained results show that the one non-linker analog 6h and two amide-based linkers 6i and 6q were the most active compounds with IC50 values of 5.08, 3.16, and 7.55 µM, respectively, against the viral protease in comparison to data of the selective antiviral agent GC-376. Molecular modeling studies were done for compound placement within the binding pocket of protease which reveal conserved residues hydrogen bonding and non-hydrogen interactions of 6i analog fragments: triazole scaffold, aryl part, and linker. Moreover, the stability of compounds and their interactions with the target pocket were also studied and analyzed by molecular dynamic simulations. The physicochemical and toxicity profiles were predicted, and the results show that compounds behave as an antiviral activity with low or no cellular or organ toxicity. All research results point to the potential usage of new chemotype potent derivatives as promising leads to be explored in vivo that might open the door to rational drug development of SARS-CoV-2 Main protease potent medicines.

Pyrazole, imidazole and triazole: In silico, docking and ADMET studies against SARS-CoV-2.

The Coronavirus pandemic, Covid-19 and SARS-Cov-2 put multidisciplinary research by chemists, biologists, pharmacists and theorists necessary and primordial task to find new active biomolecules which will be beneficial for all humanity. The azoles drugs are electronic rich, they should be used with caution, and an understanding of their pharmacokinetic profile, safety, absorption, distribution, excretion, metabolism, toxicity, and drug-drug interaction profiles is important to provide effective and cure therapy. In these objectives and goals, twenty aromatic nitrogen heterocycle compounds were chosen for in silico, docking and AMET studies against SARS-CoV-2. In this paper with respect to the protein S of SARS-CoV-2 properties, the GAUSSIAN 09w program used in the semi-empirical method at the AM1 level with the optimization of the geometry of the structures. Then Toxicity and physicochemical properties were evaluated by AMET. Molecular docking investigations conducted; the binding affinities as well as interactions of the sieve compounds with the SRAS-CoV-2 protein Spike using PyRx software. In general, the preliminary results are fructuous and needs further in vitro testes.

Synthesis and molecular docking and of new 1,2,3-triazole carbohydrates with COVID-19 proteins.

AIMS: With this aim, we have established this paper to recommend a novel way for the preparation of carbohydrates encompassing a 1,2,3-triazole motif that were prepared using an efficient click chemistry synthesis. BACKGROUND: The SARS-CoV-2 coronavirus epidemic continues to spread at a fast rate worldwide. The main protease (Mpro) is a gorgeous target for anti-COVID-19 agents. Triazoles are frequently found in many bioactive products such as coronavirus inhibitors. OBJECTIVE: Click reactions are facilitated via the activation of copper nanoparticles, different substrates have been tested using this adopted procedure given in all cases, in high yields and purity. Other interesting comparative docking analyzes will be the focus of this article. Calculations of quantitative structure-activity relationships will be studied. METHOD: Copper nanoparticles were produced by the reaction of cupric acetate monohydrate with oleylamine and oleic acid. To a solution 5-(azidomethyl)-2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran 2 (200 mg, 0.72 mmol, 1 eq.) in toluene (15 mL) was added (1.5 eq.) of N-(prop-2-yn-1-yl)benzamide derivatives 1a-d, copper nanoparticles (0.57 mg, 0.036 mmol, 0.05 eq.). RESULT: A novel series of 1,2,3-triazole carbohydrate skeletons were modeled and efficiently synthesized. Based on the observations of virtual screening established using molecular docking performed to identify novel compounds that can be able to bind with the protein structures of COVID-19 (PDB ID: 6LU7 and 6W41), we believed that the 1,2,3-triazole carbohydrate derivatives could aid in COVID-19 drug discovery. CONCLUSION: The formations of targeted triazoles were confirmed by different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and CHN analysis). The docking scores of the newly synthesized triazole are maybe attributed to the presence of hydrogen bonds together with many interactions between the ligands and the active amino acid residue of the receptor. The comparison of the interactions of remdesivir drug and triazole in the largest pocket of 6W41 and 6LU7 is also presented.

A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins.

Synthesis, characterization and theoretical studies of a novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1), which was fabricated from 4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazole-3-thiol and 4-(chloromethyl)-6,7-dimethyl-2H-chromen-2-one, are reported. The resulting compound was characterized by microanalysis, IR, 1H, and 13C APT NMR spectroscopy. The DFT calculations examined the structure and electronic properties of 1 in gas phase. Its reactivity descriptors and molecular electrostatic potential revealed the reactivity and the reactive centers of 1. ADMET properties of 1 were evaluated using the respective online tools. It was established that 1 exhibit positive gastrointestinal absorption properties and negative human blood-brain barrier penetration. The Toxicity Model Report revealed that 1 belongs to toxicity class 4. Molecular docking was additionally applied to study the interaction of 1 with some SARS-CoV-2 proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with Papain-like protease (PLpro). The interaction of 1 with the applied proteins was also studied using molecular dynamics simulations. Graphical abstract: A novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1) is reported. The structure and electronic properties of 1 were examined by the DFT calculations. ADMET properties of 1 were also evaluated. Molecular docking and molecular dynamics simulations were applied to study interactions of 1 with a series of the SARS-CoV-2 proteins. Supplementary Information: The online version contains supplementary material available at 10.1007/s12039-022-02127-0.

Advancements and Future Perspectives of 1, 2, 3 Triazole Scaffold as Promising Antiviral Agent in Drug Discovery

Severe viral infections like Covid-19 are emerging now a day and are the common causes of human illness and death. Presently, we have a limited availability of antiviral chemotherapeutic agents to prevent and treat these infections, so it is the need of an hour to develop potential antiviral drugs against various harmful and fatal viral infections. A large quantity of research has been performed on 1, 2, 3 triazole and their derivatives, which has proved the promising antiviral activity of this heterocyclic nucleus. Among nitrogen-containing heterocyclic compounds, 1, 2, 3-triazoles are privileged structure motifs and received great attention in academics and industry. Even though absent in nature, 1, 2, 3-triazoles have found broad applications in drug discovery, organic synthesis, polymer chemistry, supramolecular chemistry, bioconjugation, chemical biology, fluorescent imaging, and materials science. 1, 2, 3 triazole nucleus is one of the most important and well-known heterocycle which is a common and integral skeleton of a variety of medicinal compounds like antidepressant, antihistaminic, antioxidant, antitubercular, anti-Parkinson, antineoplastic, antihypertensive, antimalarial, local anaesthetic, antianxiety, antiobesity and immunomodulatory agents, etc. 1, 2, 3 triazole emerged as a pharmacologically significant scaffolds due to its broad and potent activity against severe infections. This review primarily lays emphasis on the recent advancements in the synthesis and biological evaluation of 1, 2, 3 triazole derivatives as antiviral agents which may facilitate the development of more potent and effective antiviral agents. Copyright © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Microwave-assisted synthesis of (6-((1-(4-aminophenyl)-1H-1,2,3-triazol-4-yl)methoxy)substituted benzofuran-2-yl)(phenyl)methanones, evaluation of in vitro anticancer, antimicrobial activities and molecular docking on COVID-19

A series of 4-Aminophenyl-1H 1,2,3-traizole based benzofuran analogs were synthesized with high yields straightforwardly via microwave irradiation methods than conventional methods. The structures of synthesized compounds were confirmed based on IR, 1H, 13C NMR, and HR mass spectral analysis. All the synthesized compounds were subjected to evaluation of their in vitro anticancer activity with MCF-7, PC-3, and HeLa cell lines by MTT assay, and compounds 7m, 7j, 7e, 7g, 7b, 7h, and 7c have shown good results compared to standard Doxorubicin. Further, in vitro antimicrobial activity of synthesized compounds examined by Agar Disc Diffusion method by taking gram-positive, gram-negative bacterial, and fungal strains and turned out with encouraging results compared to standard Ciprofloxacin and Fluconazole respectively. Furthermore, molecular docking studies were carried out to find out H-bonding interactions, hydrophobic interaction with docking scores of synthesized compounds. We have carried out molecular docking on COVID-19 study with COVID-19 main protease enzyme and got outstanding binding interactions. © 2022

In Silico Interactions of Some of the Triazole Derivatives with the Main Protease of Coronavirus

This work was done to assess in silico interactions of some of the 1,2,4-triazole derivatives with the main protease (MPro) of coronavirus to approach insights into enzymatic activity inhibition. Fifteen models of triazole derivatives (T2-T16) were investigated in this work to examine such benefits of structural modifications of T1 for approaching better ligand structures. The density functional theory (DFT) calculations indicated that the derivative ligand models were in their new characteristic specifications compared with the original T1 ligand and other T ligands. One important point was that the derivatives ligands were in higher levels of activity in comparison with the original T1 affirming the benefits of employing such structural modifications. Next, the results of molecular docking simulations indicated the potential of derivative ligands for participating in efficient interactions with the MPro target of coronavirus. As a result, the ligand models were stabilized. Their interactions with the MPro of coronavirus revealed that the investigated triazole derivatives could be considered possible inhibitors of MPro of coronavirus. © 2022 by the authors.

In vitro, in silico and Pharmaco-toxicological Efficiencies of some Triazole Derivatives on Inhibition of Digestive Enzyme Alpha-amylase

Obesity is one of the main health problems associated with a range of diseases. Genetic disposition is related to the risk for obesity but external conditions such lifestyle also increase the incidence. Current COVID-19 pandemic conditions around the globe have been reported to increase the cases of Type-2 diabetes mellitus (T2DM) due to prolonged sedentary life. Among the various treatment modalities, applications of alpha-amylase inhibitors are commonly used worldwide. Commercially available anti-diabetic drugs are potent inhibitors of alpha-amylase that reduce postprandial hyperglycemia. In this study, alpha-amylase inhibition efficiencies of some 1,2,4-triazole derivatives were evaluated. Furthermore, it has been attempted to determine the possible inhibition mechanism of the strongest inhibitor compound among the 8 candidate molecules for alpha-amylase. Compound VII showed the strongest inhibition on alpha-amylase activity with low IC50 value (150 mu M). An inhibitory kinetic analysis on alpha-amylase activity by Compound VII was found to be reversible and uncompetitive. Furthermore, molecular docking studies with this molecule showed that it could bind to the catalytic site of the enzyme by performing weak interactions with Ser56, Tyr59, Tyr62, Asp176, Asp274 and Leu142 residues. Cytotoxic potential of Compound VII on amylase overexpressing AR42J pancreatic cancer cells was also performed using trypan blue staining and the compound at the highest dose 10 mu M was found to be cytotoxic, but effective for alpha amylase inhibition at non-cytotoxic doses. The results showed in vitro effect of Compound VII on alpha-amylase inhibition in cells. Here, we suggest an alternative and non-cytotoxic alpha-amylase inhibitor for T2DM.

1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants.

SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and Omicron spike proteins, in comparison to the reference drugs. In particular, compound 9 has the highest scoring affinity against the SARS-CoV-2 and Omicron spike proteins in vitro with its IC50 reaching 75.98 nM against the Omicron spike protein and 74.51 nM against the SARS-CoV-2 spike protein. The possible interaction between the synthesized triazoles and the viral spike proteins was by the prevention of the viral entry into the host cells, which led to a reduction in viral reproduction and infection. A cytopathic inhibition assay in the human airway epithelial cell line (Vero E6) infected with SARS-CoV-2 revealed the effectiveness and safety of the synthesized compound (compound 9) (EC50 and CC50 reached 80.4 and 1028.28 µg/mL, respectively, with a selectivity index of 12.78). Moreover, the antiinflammatory effect of the tested compound may pave the way to reduce the reported SARS-CoV-2-induced hyperinflammation.

Theoretical Description for Anti-COVID-19 Drug Molnupiravir Electrochemical Determination over the Poly-((1,2,4-triazole)-co-(squaraine dye)) Composite with Cobalt (III) Oxyhydroxide

The possibility of electrochemical determination of molnupiravir has been theoretically evaluated for the first time. The molnupiravir electrochemical oxidation over the poly((1,2,4-triazole)-co-(squaraine dye)) composite with cobalt (III) oxyhydroxide has been theoretically evaluated. The correspondent mathematical model analysis has shown that the composite is an efficient electrode modifier for molnupiravir electrochemical determination. As for the oscillatory behavior is more probable than for the simplest case, and its probability will be higher in alkaline media than in neutral.

Triazoles and Their Derivatives: Chemistry, Synthesis, and Therapeutic Applications.

Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered triazoles: 1,2,3-triazole and 1,2,4-triazole. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities. These are also important in organocatalysis, agrochemicals, and materials science. Thus, they have a broad range of therapeutic applications with ever-widening future scope across scientific disciplines. However, adverse events such as hepatotoxicity and hormonal problems lead to a careful revision of the azole family to obtain higher efficacy with minimum side effects. This review focuses on the structural features, synthesis, and notable therapeutic applications of triazoles and related compounds.

Probing the Action of Screened Anticancer Triazole–Tetrazole Derivatives Against COVID-19 Using Molecular Docking and DFT Investigations

Drugs are continuously being evaluated for novel therapeutic uses. The purpose of this work was to screen anticancer triazole/tetrazole derivatives for effectiveness against the SARS-CoV-2 main protease (Mpro). First, the chemical structures’ activity was derived from conceptual quantum chemical calculations. According to molecular docking analysis, the compounds scored good interactions against SAR-COV-2's Mpro, with binding energies extending from −8.21 to −8.97 kcal/mol. The docked complexes included various bindings with His41 and Cys145, both catalytic residues responsible for cleavage of the SARS-CoV-2 Mpro. Among the 4 studied compounds, TD3 exhibited the highest affinity by achieving the most stable binding energy and lowest value for the inhibition constant. Most striking was that TD3 not only formed strong bonds with the catalytic residues His41 and Cys145, but also captured the residues of the catalytic loop (Cys44 to Pro52), which flank the catalytic dyads in Mpro's active site. As a result, the studied triazole/tetrazole derivatives, notably TD3, must be reviewed as potent drugs that could be repurposed for SARS-CoV-2 treatment.

Synthesis, crystal structure elucidation, DFT analysis, drug-likeness and ADMET evaluation and molecular docking studies of triazole derivatives: Binary inhibition of spike protein and ACE2 receptor protein of COVID-19.

The recent incidence of terrible acute respiratory syndrome coronavirus 2 (SARS CoV-2) has presently experienced some noteworthy mutations since its discovery in 2019 in Wuhan, China. The present research work focuses on the synthesis of three triazole derivatives (BMTPP, BMTTP, and BMTIP) and their inhibition activities against SARS-Cov-2 spike and ACE2 receptor proteins. The crystal structure for BMTTP was determined by the SCXRD method and optimized geometrical parameters for the three triazole derivatives were obtained by DFT calculations. HOMO-LUMO, Global reactive descriptors [GRD], and Molecular electrostatic potential (MEP) investigations exposed that all three compounds have biological properties. The drug-likeness ability of the synthesized compounds was examined using Molinspiration and a pre-ADMET online Server. Further, to explore the binding nature of three synthesized compounds with SARS-Cov-2 spike proteins/ACE2 receptor molecular docking studies were executed. The outcomes we obtained from molecular docking simulation studies suggest that the synthesized triazole derivatives may be well utilized as curing medicines against COVID-19. Ultimately, animal tests and precise clinical tests are required to prove the potent nature of these compounds against COVID-19. Finally, the present outcomes must be proved to utilize in-vitro and in-vivo antiviral methods.

Synthesis, spectroscopic characterization of novel phthalimides derivatives bearing a 1,2,3-triazole unit and examination as potential SARS-CoV-2 inhibitors via in silico studies.

In the present study, novel phthalimide derivatives 8(a-f) and 9(a-f) bearing a 1,2,3-triazole subunit were synthesized via CuAAC reactions and characterized by 1H, 13C NMR, HR-MS, and FT-IR analyses. To support the fight against SARS-CoV-2, in silico molecular docking studies were carried out to examine their interactions with the proteins of SARS-CoV-2 (Mpro and PLpro) and the protein-protein interactions (PPI) between the ACE2-spike (S1) in comparison with various inhibitors reported to be active by in vitro experiments. The ligand-protein stabilities of compounds 8a-Mpro, 8b-PLpro, and 9a-'ACE2-S1' showing the best binding energy and predicted inhibition constant values (Ki) were examined by molecular dynamics simulation studies. Finally, in silico ADMET properties of the target compounds were investigated using the Swiss ADME and ProTox-II web tools. According to in silico results, all phthalimide analogs may block the PPI between S1 and ACE2. The compounds may also inhibit the progression of the Mpro, and PLpro proteins of SARS-CoV-2. Additionally, it has been estimated that the compounds are suitable for oral administration and exhibit low levels of toxicity.

New experimental low-cost nanoscience technology for formulation of silver nanoparticles-activated carbon composite as a promising antiviral, biocide, and efficient catalyst

A simple low-cost one-pot photodeposition synthesis with no hazardous reactants or products is used to make silver nanoparticles-activated carbon composite (SNPs@AC). The SNPs are homogenously and photodeposited and absorbed into the activated carbon matrix. Both SNPs and SNPs@AC composite have particle sizes around 10 nm and 100 nm, respectively. The SNPs@AC composite showed good antiviral activity to VERO (ATCC ccl-81) cells. Zeta potential of SNPs@AC composite is −25 mV, showing that this colloidal system is electrically stable and resistant to coagulation. For many Gram-positive and Gram-negative bacteria, the SNPs@AC composite demonstrated strong antibacterial efficacy. The SNPs@AC composite has 75.72 percent anti-inflammatory effect at concentration 500 µg/mL. This composite has a maximum non-toxic concentration (MNTC) of 78.125 g/mL, which corresponds to antiviral activity of up to 96.7 percent against hepatitis A. virus (HAV). It is suggested as a candidate for pharmaceutical formulations, such as integration into the manufacture of N95 masks for COVID-19 infection protection. Concentration 160 μg/mL SNPs@AC composite has antioxidant activity 42.74% percent. The SNPs@AC composite exhibited selective catalytic activity for the organosynthesis hydrazination reaction of 4-chloro-3, 5-di-nitro-benzo-triflouride, giving 1-hydroxy-4-nitro-6-trifluoro-methyl benzotriazole, a common antiviral drug for severe acute respiratory syndrome (SARS). SNPs@composite's well-defined pores provide suitable active sites for binding reactants: 4-Cl-3, 5-di-NO2-benzotriflouride, and hydrazine, which react to create 1-hydroxy-4-nitro-6-trifluoromethyl benzotriazole, which diffuses into solution away from the catalyst surface, leaving the catalyst surface unaffected.

Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations.

BACKGROUND: The SARS-CoV-2 main protease (Mpro) is an attractive target in the COVID-19 drug development process. It catalyzes the polyprotein's translation from viral RNA and specifies a particular cleavage site. Due to the absence of identical cleavage specificity in human cell proteases, targeting Mpro with chemical compounds can obstruct the replication of the virus. METHODS: To explore the potential binding mechanisms of 1,2,3-triazole scaffolds in comparison to co-crystallized inhibitors 11a and 11b towards Mpro, we herein utilized molecular dynamics and enhanced sampling simulation studies. RESULTS AND CONCLUSION: All the 1,2,3-triazole scaffolds interacted with catalytic residues (Cys145 and His41) and binding pocket residues of Mpro involving Met165, Glu166, Ser144, Gln189, His163, and Met49. Furthermore, the adequate binding free energy and potential mean force of the topmost compound 3h was comparable to the experimental inhibitors 11a and 11b of Mpro. Overall, the current analysis could be beneficial in developing the SARS-CoV-2 Mpro potential inhibitors.