Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

<p>Nowadays, many people were dying due to infectious coronavirus diseases (COVID-19). It belongs to the betacoronavirus family and also known as SARS-CoV-2. However, COVID-19 is a new form that has some basic difference in the genome which makes it more lethal and infectious. In transmitted in human in late December 2019 and it infected about 20 million till date. Its genome is composed of positive-sense single-stranded RNA, which encodes for the poly-protein. This poly-protein further cleaved into various components of the virus to make the numerous copy of the virus. There are many more similarities in their genome among the SARS-CoV-2, SARS-CoV, MERS-CoV. However, protease proteins are responsible for the cleavage and hence, COVID-19 main protease is a prime therapeutic target. To date, no medicine/ vaccine can fully cure their infection. To inhibit the activity of protease of COVID-19, molecular docking and ADMET studies of 116 noscapine derivatives were performed and the result was compared with 14 reputed antiviral drugs including chloroquine and hydroxychloroquine. The molecular docking result indicates a better binding in comparison of 14 reputed drugs. Further, the top six noscapines was taken into consideration for the pose analysis and ADMET studies. Finally, the top six noscapine was refined by ADMET properties to get the most potent one.</p>

Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

<p>Nowadays, many people were dying due to infectious coronavirus diseases (COVID-19). It belongs to the betacoronavirus family and also known as SARS-CoV-2. However, COVID-19 is a new form that has some basic difference in the genome which makes it more lethal and infectious. In transmitted in human in late December 2019 and it infected about 20 million till date. Its genome is composed of positive-sense single-stranded RNA, which encodes for the poly-protein. This poly-protein further cleaved into various components of the virus to make the numerous copy of the virus. There are many more similarities in their genome among the SARS-CoV-2, SARS-CoV, MERS-CoV. However, protease proteins are responsible for the cleavage and hence, COVID-19 main protease is a prime therapeutic target. To date, no medicine/ vaccine can fully cure their infection. To inhibit the activity of protease of COVID-19, molecular docking and ADMET studies of 116 noscapine derivatives were performed and the result was compared with 14 reputed antiviral drugs including chloroquine and hydroxychloroquine. The molecular docking result indicates a better binding in comparison of 14 reputed drugs. Further, the top six noscapines was taken into consideration for the pose analysis and ADMET studies. Finally, the top six noscapine was refined by ADMET properties to get the most potent one.</p>

Docking, Synthesis and Antimalarial Evaluation of Hybrid Phenyl Thiazole 1,3,5-Triazine Derivatives

Background: Presentlytheeffectiveness of antifolate antimalarial drugs is decreasing due to the emergence of resistant Plasmodium strains. The aim of the present study was to determine the antimalarial effect of hybrid p-bromo phenyl thiazole-triazine derivatives against 3D7 strain of Plasmodium falciparum. Methods: Seventy-fivehybrid derivativeswere designed based on the lead molecule and docking was done against the active site of Pf-DHFR-TS (PDB i.d. 1J3i) with validated ligand fit protocol by using Discovery Studio 2.5. Based on the highest binding energy and the best docked pose, fifteen compounds were selected for the synthesis. Synthesized compounds were characterized by different spectroscopy methods and in-vitro antimalarial evaluation was done against the 3D7 strain of Plasmodium falciparum. Results: Fifteen compounds were synthesized by conventional and microwave assisted method and were characterized byFT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy. In-vitro antimalarial screening results showed that compounds ADG303, ADG 306 and ADG 302 have the highest activity against 3D7 strain of P. falciparum. Furthermore, docking result of these compounds having binding energies of -154.91, -165.981, -137.826 respectively showed similarity with reference compound WR99210 (-152.023) and also bound to Asp54 and Phe 58 amino acid at the active site of the receptor. Conclusion: The synthesized compound ADG303 exhibited an encouraging result which could be a new lead for antimalarial drug discovery.

Structural Deviation and Identification of Novel Inhibitor of SARS-CoV-2 Spike Protein Through Molecular Docking: An In Silico Study

Purpose: Pandemic Novel Coronavirus (SARS-CoV-2) has emerger centered from wuhan, China. Structurally homologous spike protein of SARS-CoV-2 receptor is taxonomically homologous with SARS-Cov and SARS associated bat coronavirus. Still now scientists are trying to find out proper vaccine and treatments for this disease. Methods: Systematically we modeled and compared the structure of SARS-CoV-2 spike protein along with Bat Cov, Bat SARS Cov and SARS Cov Urbani. S1 and S2 unit of the coronavirus (SARS-CoV-2) are attached with ACE2 and furin, here we docked 5 Ca+ chelating drugs with these two proteins. Results: Structural comparison with all these spike proteins revealed that less significant but not negligible difference exists among them. Inserted stable nucleotide sequences and corresponding surface exposed peptidal region may be considered as epitope. Docking result with Toxicokinetics and half life of Penicillamine can effectly inhibit the attachment site of spike protein of coronavirus (SARS-CoV-2). Conclusions: Docking summery and the pharmacokinetics with toxicokinetics index recommend that Penicillamine can able to inhibit the infection of SARS-CoV-2.

One-Pot Three Component Synthesis of 2-(1H-Benzo[d]thiazole-2-yl)- N-Arylbenzamides in Glycerol Medium

In this work, a series of 2-(1H-benzo[d]thiazole-2-yl)-N-arylbenzamides is synthesized by using diethyl phthalate, anilines and 2-amino-benzenethiol by one-pot three component synthesis in glycerol medium. Phosphoric acid is used as an effective reagent for this one-pot three component reaction. This reaction got completed in a short time, easy workup and gave an excellent yield in glycerol medium. The N-arylbenzamides was found to have significant cytotoxic potentials against various cancer cells viz., A549 (lung cancer), HeLa (cervical cancer) and MCF-7 (breast cancer) using MTT assay. The molecular docking study is also employed to understand the binding mechanism of N-arylbenzamides against the antibacterial target. The docking result shows the binding energy of compound 4a is -8.6 kcal/mol. The binding affinity is a major concern and it shows that Asn and Thr residues have an interaction with compound 4a.

Molecular Docking Studies of Phytocompounds from Aloe vera (L.) Burm.f. having Anticancer Property, against an Antiapoptotic Bcl-2 Protein

ABSTRACT: B-cell lymphocyte-2 (Bcl-2) is an antiapoptotic protein, which is an important member of Bcl-2 family. The current study involves molecular docking of six antineoplastic phytocompounds from Aloe vera (L.) Burm.f. against the protein Bcl-2. Docetaxel, a known inhibitor of Bcl-2 was used as a control in this study. All the studied phytocompounds bound within the same binding pocket as that of Docetaxel and thus can be considered as potential inhibitors of Bcl-2 protein. Among the six phytocompounds studied, AVG4 showed the best docking result, with a minimum pharmacological energy, -198.9 kcal/mol, followed by AVG6 and AVG3 as the second and third best phytocompound while AVL3 has the maximum pharmacological energy -103.8 kcal/mol. AVL3 is involved in cation-pi interactions with the Tyr9 residue of the Bcl-2 protein which is not considered while calculating pharmacological energy scoring function. Calculation of energy due to cation-pi interactions may result in the increase in total binding energy of AVL3, which may significantly increase the pharmacological energy, EPharma by approximately -8 kcal/mol, resulting in another potential anticancer phytocompound.

IN SILICO STUDY OF APIGENIN AND APIGETRIN AS INHIBITOR OF 3-HYDROXY-3-METHYL-GLUTAYL-COENZYME A REDUCTASE

Objective: The objectives of this research were to investigate in silico interaction between apigenin and apigetrin with 3-hydroxy-3-methyl-glutayl-coenzyme A (HMG Co-A) reductase, to find the most favorable binding site as well as to predict the binding mode.Materials and Methods: Docking calculation was performed by branded Sony Vaio PC Linux Ubuntu 14.04 LTS. The binding process based on the best docking result with HMG Co-A reductase was presented in two-dimensional diagram. Statin, atorvastatin, and R-mevalonate were used as standard.Results: Binding affinity and inhibition constant of R-mevalonate were Ei=−4.2 kcal/mol, Ki=836.78 μM; apigenin Ei=−7.0 kcal/mol, Ki=7.43 μM; apigetrin Ei=−5.9 kcal/mol, Ki=47.53 μM; simvastatin Ei=−8.2 kcal/mol; Ki=0.98 μM; atorvastatin Ei=−8.4 kcal/mol; Ki=0.7 μM. Apigenin had better binding interaction than apigetrin.Conclusion: Apigenin could be developed as anticholesterol.

Solvent Free Synthesis and Safener Activity of Sulfonylurea Benzothiazolines

A series of novel sulfonylurea benzothiazoline were designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All the compounds were characterized by IR, 1H-NMR, 13C-NMR, HRMS. The biological activity tests indicated the compounds could protect maize against the injury caused by chlorsulfuron to some extent. The molecular docking result showed that the new compound competed with chlorosulfuron to bind with the herbicide target enzyme active site to attain detoxification.

Jatrorrhizine hydrochloride potentiates the neuraminidase inhibitory effect of oseltamivir towards H7N9 influenza

By analyzing the docking result of the binding position, hydrogen bond interactions, pi–pi interaction, etc., it is likely that jatrorrhizine hydrochloride potentiates the neuraminidase inhibitory effect of oseltamivir towards H7N9 influenza.

Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking

Metuximab is the generic name of Licartin, a new drug for radioimmunotherapy of hepatocellular carcinoma. Although it is known to be a mouse monoclonal antibody against CD147, the complete epitope mediating the binding of metuximab to CD147 remains unknown. We panned the Ph.D.-12 phage display peptide library against metuximab and got six mimotopes. The following bioinformatics analysis based on mimotopes suggested that metuximab recognizes a conformational epitope composed of more than 20 residues. The residues of its epitope may include T28, V30, K36, L38, K57, F74, D77, S78, D79, D80, Q81, G83, S86, N98, Q100, L101, H102, G103, P104, V131, P132, and K191. The homology modeling of metuximab and the docking of CD147 to metuximab were also performed. Based on the top one docking model, the epitope was predicted to contain 28 residues: AGTVFTTV (23–30), I37, D45, E84, V88, EPMGTANIQLH (92–102), VPP (131–133), Q164, and K191. Almost half of the residues predicted on the basis of mimotope analysis also appear in the docking result, indicating that both results are reliable. As the predicted epitopes of metuximab largely overlap with interfaces of CD147-CD147 interactions, a structural mechanism of metuximab is proposed as blocking the formation of CD147 dimer.