Implementation and Application of Large-Scale Drug Virtual Screening

The molecular docking-based virtual screening technique evaluates the binding abilities between multiple ligand compounds and receptors to screen for the active compounds. In the context of the global spread of the COVID-19 pandemic, large-scale and rapid drug virtual screening is crucial for identifying potential drug molecules from massive datasets of ligand structures. The powerful computing power of supercomputer provides hardware guarantee for drug virtual screening, but the super large-scale drug virtual screening still faces many challenges that affects the effective execution of the calculation. Based on the analysis of the challenges, this paper proposes a centralized task distribution scheme with a central database, and designs a multi-level task distribution framework. The challenges are effectively solved through multi-level intelligent scheduling, multi-level compression processing of massive small molecule files, dynamic load balancing and high error tolerance management technology. An easy-touse"tree”multi-level task distribution system is implemented. A fast, efficient and stable drug virtual screening task distribution, calculation and result analysis function is realized, and the computing efficiency is nearly linear. Then, heterogeneous computing technology is used to complete the drug virtual screening of more than 2 billion compounds, for two different active sites for COVID-19, on the domestic super computing system, which provides a powerful computing guarantee for the super large-scale rapid virtual screening of explosive malignant infectious diseases. © 2023, Journal of Computer Engineering and Applications Beijing Co., Ltd.;Science Press. All rights reserved.

Study on potential common action and mechanism of Reduning Injection against SARS, MERS and COVID-19 based on network pharmacology and molecular docking technology.

Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.

Discover the Medication Potential of Algerian Medicinal Plants Against Sars-Cov-2 Main Protease (Mpro): Molecular Docking, Molecular Dynamic Simulation, and ADMET Analysis

At the end of 2019, the world faced a big challenge and crisis caused by the SARS-CoV-2 virus. It spreads rapidly and is contagious;no treatment has officially been found. Algeria has used medicinal plants native to the country to defend against this pandemic. The objective of this paper is based on a molecular docking study of the active compounds of five Algerian medicinal plants with their target Sars-2Cov-2 virus protease to assess their potential antiviral activity against COVID-19. Innovative software and computerized databases were introduced into the in-silico domain, mainly the Auto-Dock software version 1.5.6. Similar results were obtained for all ligands, with a better chemical affinity of − 5.600 kcal/mol for the protease target 6LU7 and − 5.700 kcal/mol for the protease target 6WTT, with an average of − 4.227 kcal/mol and − 4.221 kcal/mol, respectively. The protease targets 6LU7 and 6WTT. In the ADME-Tox study, the active compounds of Algerian medicinal plants also demonstrated an excellent pharmacokinetic and toxic profile. Best scores were noted for cedrol, camphor, and eucalyptol. A molecular dynamics simulation showed the stability of camphor-6LU7 and cedrol-6LU7 complexes, favoring the biological potential of white artemisia and cypress plants. Graphical : [Figure not available: see fulltext.] © 2023, This is a U.S. Government work and not under copyright protection in the US;foreign copyright protection may apply.

Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro.

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHOD(S): The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULT(S): Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 mug/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 mug/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 mumol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 mumol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro. CONCLUSION(S): Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.

Inhibition of Spike Protein of SARS-CoV2 from (Merremia mammosa (Lour) Hall. F.) Bioactive Compounds: Molecular Docking and ADMET Study

Spike protein is a receptor protein that has e role in the entry step of SARS-CoV2. This protein will bind to the ACE2 receptor in the human body and activate TMPRSS2. Inhibition of this protein will prevent the binding of the virus to host cells to spread the infection. This study aims to identify the activity of bioactive compounds of Merremia mammosa (Lour) tuber obtained from LC-MS/MS QTOF analysis of a previous study against the Spike protein of SARS-CoV2 using molecular docking and ADMET analysis. Molecular docking was conducted using SARS-CoV2 spike protein (PDB id. 6M0J) using Maestro Schrodinger software. Results showed that from 206 compounds there are 8 compounds of Merremia mammosa (Lour) that have lower predictive binding energies than standard drugs arbidol, hydroxychloroquine, and chloroquine. Result(s): 206 compounds of Merremia mammosa (Lour) tuber were successfully docked, there were 8 compounds that have docking scores more negative than standard drugs. It indicates that 8 compounds are more active than the positive controls. ADMET study revealed all of those potential ligands had the possibility to be developed as drugs. Conclusion(s): Molecular docking simulations were successfully utilized to identify the potential compounds from Merremia mammosa (Lour) tuber with the activity as an inhibitor for spike protein of SARS-CoV2. Further in vitro assay and purification are needed for future research.Copyright © 2021 Muslim OT et al.

A comprehensive review on technological advances in alternate drug discovery process:Drug repurposing

The traditional de novo drug discovery is time consuming, costly and in some instances the drugs will fail to treat the disease which result in a huge loss to the organization. Drug repurposing is an alternative drug discovery process to overcome the limitations of the De novo drug discovery process. Ithelps for the identification of drugs to the rare diseases as well as in the pandemic situationwithin short span of time in a cost-effective way. The underlying principle of drug repurposing is that most of the drugs identified on a primary purpose have shown to treat other diseases also. One such example is Tocilizumab is primarily used for rheumatoid arthritis and it is repurposed to treat cancer and COVID-19. At present, nearly30% of the FDA approved drugs to treat various diseases are repurposed drugs. The drug repurposing is either drug-centric or disease centric and can be studied by using both experimental and in silico studies. The in silico repurpose drug discovery process is more efficient as it screens thousands of compounds from the diverse libraries within few days by various computational methods like Virtual screening, Docking, MD simulations,Machine Learning, Artificial Intelligence, Genome Wide Association Studies (GWAS), etc. with certain limitations.These limitationscan be addressed by effective integration of advanced technologies to identify a novel multi-purpose drug.Copyright © 2023, Association of Biotechnology and Pharmacy. All rights reserved.

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).

In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors

Background: The emergence of Coronavirus disease (COVID-19) has been declared a pandemic and made a medical emergency worldwide. Various attempts have been made, including optimizing effective treatments against the disease or developing a vaccine. Since the SARS-CoV-2 protease crystal structure has been discovered, searching for its inhibitors by in silico technique becomes possible. Objective(s): This study aims to virtually screen the potential of phytoconstituents from the Begonia genus as 3Cl pro-SARS-CoV- 2 inhibitors, based on its crucial role in viral replication, hence making these proteases "promising" for the anti-SARS-CoV-2 target. Method(s): In silico screening was carried out by molecular docking on the web-based program DockThor and validated by a retrospective method. Predictive binding affinity (Dock Score) was used for scoring the compounds. Further molecular dynamics on Desmond was performed to assess the complex stability. Result(s): Virtual screening protocol was valid with the area under curve value 0.913. Molecular docking revealed only beta-sitosterol-3-O-beta-D-glucopyranoside with a lower docking score of -9.712 kcal/mol than positive control of indinavir. The molecular dynamic study showed that the compound was stable for the first 30 ns simulations time with Root Mean Square Deviation <3 A, despite minor fluctuations observed at the end of simulation times. Root Mean Square Fluctuation of catalytic sites HIS41 and CYS145 was 0.756 A and 0.773 A, respectively. Conclusion(s): This result suggests that beta-sitosterol-3-O-beta-Dglucopyranoside might be a prospective metabolite compound that can be developed as anti-SARS-CoV-2.Copyright © 2023, Page Press Publications. All rights reserved.

Current status and hotspot of Lonicera Japonica Flos research based on bibliometrics.

In order to comprehensively understand the research hotspots and development trends of Lonicera Japonica Flos in the past 20 years, and to provide intuitive data reference and objective opinions and suggestions for subsequent related research in this field, this study collected 8 871 Chinese literature and 311 English literature related to Lonicera Japonica Flos research in the core collection databases of Wanfang Data), CNKI and Web of Science (WOS) from 2002 to 2021, and conducted bibliometric and visual analysis using vosviewer. The results showed that the research on the active components of Lonicera Japonica Flos based on phenolic acid components, the research on the mechanism of novel coronavirus pneumonia based on data mining and molecular docking technology, and the pharmacological research on the anti-inflammatory and antiviral properties of Lonicera Japonica Flos are the three hot research directions in the may become the future research direction. In this paper, we analyze the research on Lonicera Japonica Flos from five aspects: active ingredients, research methods, formulation and preparation, pharmacological effects and clinical applications, aiming to reveal the research hotspots, frontiers and development trends in this field and provide predictions and references for future research.Copyright © Drug Evaluation Research 2022.

A phenoxy-bridged trinuclear Ni(ii) complex: synthesis, structural elucidation and molecular docking with viral proteins

A novel phenoxy-bridged trinuclear nickel(ii) complex [Ni3(mu-L)2(bipy)3](1) (where H3L= (E)-2-hydroxy-N-(2-hydroxy-3,5-diiodophenyl)-3,5-diiodobenzohydrazonic acid, bipy = 2,2'-bipyridyl) has been designed and synthesized as a potential antivirus drug candidate. The trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) was fully characterized via single crystal X-ray crystallography. The unique structure of the trinuclear nickel(ii) complex crystallized in a trigonal crystal system with P3221 space group and revealed distorted octahedral coordination geometry around each Ni(ii) ion. The X-ray diffraction analysis established the existence of a new kind of trinuclear metal system containing nickel(ii)-nickel(ii) interactions with an overall octahedral-like geometry about the nickel(ii) atoms. The non-bonded Ni-Ni distance seems to be 3.067 and 4.455 A from the nearest nickel atoms. The detailed structural analysis and non-covalent supramolecular interactions are also investigated by single crystal structure analysis and computational approaches. Hirshfeld surfaces (HSs) and 2D fingerprint plots (FPs) have been explored in the crystal structure to investigate the intermolecular interactions. The preliminary analysis of redox and magnetic characterization was conducted using cyclic voltammetry measurements and a vibrating sample magnetometer (VSM), respectively. This unique structure shows good inhibition performance for SARS-CoV-2, Omicron and HIV viruses. For insight into the potential application of the Ni(ii) coordination complex as an effective antivirus drug, we have examined the molecular docking of the trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) with the receptor binding domain (RBD) from SARS-CoV-2 (PDB ID: 7MZF), Omicron BA.3 variant spike (PDB ID: 7XIZ), and HIV protease (PDB ID: 7WCQ) viruses. This structure shows good inhibition performance for SARS-CoV-2, Omicron S protein and HIV protease viruses;the binding energies (DELTAG) and the respective Ki/Kd (inhibition/dissociation constants) correlation values are -8.9 (2.373 muM or 2373 nM), -8.1 (1.218 muM or 1218 nM) and -7.9 (0.874 muM or 874 nM), respectively. The results could be used for rational drug design against SARS-CoV-2 Omicron variant and HIV protease viruses.Copyright © 2023 The Royal Society of Chemistry.

In silico Screening of the Potential Anti-SARS-CoV-2 Activities of Peptides from Vipera ammodytes ammodytes Venom by Molecular Docking

The coronavirus disease 2019 (COVID-19) is induced by the SARS-CoV-2 virus, which caused the global pandemic, infecting approximately 608.328.548 confirmed cases and bringing about 6.501.469 deaths worldwide, as WHO stated in September 2022. The disease is more deadly due to the lack of specific drug molecules or a treatment plan. Therefore, the development of potent pharmacological compounds is urgently required to combat COVID-19. Due to their biological actions, snake venoms constitute a source of potentially beneficial medicinal compounds. Vipera ammodytes ammodytes (VA) is a viper species whose venom has been shown to have anti-proliferative, antimetastatic, anti-cancer, and anti-microbial activities. This in silico study was conducted to evaluate the efficacy of selected VA venom proteins (Adamalysin II, Ammodytoxin A, Ammodytin L, L-amino acid oxidase) against molecular targets;Main protease (3CLpro) and Angiotensin-Converting Enzyme 2 (ACE2) by molecular docking study. Molecular docking investigations were performed by using AutoDock Vina software. All compounds displayed negative binding energy values to 3CLpro and ACE2, suggesting that their interactions with the active sites were favourable. L-amino acid oxidase had the highest binding affinity with both 3CLpro and ACE2. This study revealed for the first time that VA venom proteins are functional inhibitors of 3CLpro and ACE2 activities, and the components of VA venom can be considered potential SARS-CoV-2 inhibitors. However, more studies are needed to validate these compounds in vitro and in vivo. [ FROM AUTHOR] Copyright of Journal of the Institute of Science & Technology / Fen Bilimleri Estitüsü Dergisi is the property of Igdir University, Institute of Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Design, Spectroscopic, and Crystal Structural Characterization of New Pyrazolone-Based Schiff Bases: Molecular Docking Investigations against SARS-Covid-19 Main Proteases (PDB Ids: 6LU7 and 7TLL)

New pyrazolone-based Schiff bases were synthesized and characterized by various spectroscopic and analytical techniques such as 1H-NMR, FTIR, and UV − Vis spectroscopy and elemental analysis. Crystal structures of two of the Schiff-base (SB) compounds were obtained by single-crystal X-ray crystallography (SCXRC). The target Schiff bases were synthesized from the condensation of 4-acetyl-3-methyl-1-phenyl-5-pyrazolone with 1,2-diaminobenzene (SB1), 4-methyl-1,2-diaminobenzene (SB2), and 4,5-dimethy-1,2-diaminobenzene (SB3). Molecular docking modeling was used to study the interactions of these molecules with SARS-CoV-2 virus main proteases (PDB ids: 6LU7 and 7TLL). The estimated free binding energies (EFBE) for all the three SBs were better than the standard drugs favipiravir and dexamethasone. Besides, the order of EFBE was −7.68 (SB3)> −7.36 (SB1)> −7.06 kcal.mol−1(SB2) for 6LU7 and −10.42 (SB3)> −10.05 (SB1)> −9.69 kcal.mol−1(SB2) for 7TLL. SB3 showed the best interactions with both proteases that is discussed based on structure–function relationship.

Inhibition of SARS-CoV2 Replication Regulated by NSP3 through Ayurveda Phytoconstituents of Indian Traditional Medicine

With Covid-19, a significant proportion of the population who are already vaccinated have tested positive. Therefore, there is a need for better medicines that act against the virus rigorously without causing any side effects. We aim to achieve the same through molecular docking and further simulations for bioactive phytochemicals of ayurvedic medicinal plants. The target for this study has been considered the NSP3 protein of the viral RNA that actively takes part in both replication and immune evasion pathways of the virus. Ligand libraries consisting of bioactive phytochemicals of aswasgandha and analogues of curcumin and piperine are curated. The libraries, along with the NSP3 protein moiety are docked onto two active sites. With the best-scored complexes further taken up for molecular dynamics simulation, the study resulted in favourable outcomes for three such ligands (compound ID 5469426, 69501714, ZINC000003874317). © 2023 Bharati Vidyapeeth, New Delhi.

Research Article Molecular Docking and Drug Likeness Prediction of New Potent Sars Cov-2 Main Protease Inhibitors

The novel corona virus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. The Main protease (Mpro) plays critical role in the SARS-CoV-2 life cycle through virus replication and transcription process making it as an attractive drug target. Herein, molecular docking study followed by drug-Likeness prediction, were performed in order to identify new potent Mpro inhibitors. Indeed, molecular docking of 1880 compounds into the Mpro active site reveals compounds S1 and S2 as promising inhibitors of this enzyme with binding energy of -39,22 KJ/mol, -36.27 KJ/mol respectively. These two compounds were also predicted to have satisfying drug likeness properties, indicating that they might be promising lead compounds for further anti-SARS CoV-2 drug research.Copyright © KESS All rights reserved.

Omicron: Emergence, detection, and response

COVID-19 pandemic emerged in December 2019, and it is still a global threat with quite a few variants. The B.1.1.529, Omicron, identified in South Africa in 2021, was one of the most notorious variants due to its high infection and mutability capacity. The Omicron variant had mutations in the S region of the key RBD which boosted the transmission ability of the virus. Resistance to antibodies and vaccines has been the key features of this variant. The rise of antibody-evading variants has reached alarming proportions and discovery of small molecule inhibitors has been thought to be a solution to this problem. Presently scientific attention has been substantially directed towards computational drug design performing molecular simulations to generate effective chemical agents to tackle the Omicron variant. © 2023 Nova Science Publishers, Inc. All rights reserved.

Phytochemicals of Hibiscus sabdariffa with Therapeutic Potential against SARS-CoV-2: A Molecular Docking Study

In this study, the possible interactions of 17 phytochemicals that were reported as the most abundant biomolecules of Hibiscus sabdariffa, including many organic acids as well as catechin and quercetin derivatives, with 3CLpro and PLpro proteases of SARS-CoV-2 have been investigated via molecular docking. Caffeoylshikimic acid/3CLpro showed the lowest binding energy (-7.72 kcal/mol) with seven H-bonds. The second-lowest binding energy was computed in the chlorogenic acid/3CLpro complex (-7.18 kcal/mol), which was found to form 6 H-bonds. Also, low binding energies of cianidanol (-7.10 kcal/mol), cryptochlorogenic acid (-6.67 kcal/mol), and kaempferol (-6.82 kcal/mol) were calculated to 3CLpro with several H-bond interactions. Nelfinavir (-10.16 kcal/mol) and remdesivir (-6.40 kcal/mol), which have been used against COVID-19, were obtained to have low binding energies to 3CLpro with 3 H-bond formations each. On the other hand, the nicotiflorin/PLpro complex, which had the lowest binding energy (-7.40 kcal/mol), was found to have only 1 H-bond interaction. The secondlowest binding energy was reported in chlorogenic acid/PLpro (-7.20 kcal/mol), which was found to possess four H-bonds. On the other hand, epigallocatechin gallate/PLpro, which was shown to have a -5.95 kcal/mol binding energy, was found to form 8 H-bond interactions. Furthermore, the quercetin pentosylhexoside/PLpro complex was monitored to have low binding energy (-6.54 kcal/mol) with 9 H-bonds, which stands as the highest number of H-bonds in all complexes. Therefore, several molecules of Hibiscus sabdariffa were found to have strong binding affinity to the main proteases of SARS-CoV-2. This study suggests many compounds, including caffeoylshikimic acid and nicotiflorin, to inhibit 3CLpro and PLpro activities. As a result, numerous chemicals derived from Hibiscus sabdariffa have the potential to be employed therapeutically against SARS-CoV-2 infection. [ FROM AUTHOR] Copyright of Journal of the Institute of Science & Technology / Fen Bilimleri Estitüsü Dergisi is the property of Igdir University, Institute of Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

In silico assessment of diterpenes as potential inhibitors of SARS-COV-2 main protease

Aim: We aimed to investigate the potential inhibitory effects of diterpenes on SARS-CoV-2 main protease (Mpro). Materials & methods: We performed a virtual screening of diterpenoids against Mpro using molecular docking, molecular dynamics simulation and absorption, distribution, metabolism and excretion) analysis. Results: Some tested compounds followed Lipinski's rule and showed drug-like properties. Some diterpenoids possessed remarkable binding affinities with SARS-CoV-2 Mpro and drug-like pharmacokinetic properties. Three derivatives exhibited structural deviations lower than 1 angstrom. Conclusion: The findings of the study suggest that some of the diterpenes could be candidates as potential inhibitors for Mpro of SARS-CoV-2.

A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years.

Structure-based virtual screening (SBVS), also known as molecular docking, has been increasingly applied to discover small-molecule ligands based on the protein structures in the early stage of drug discovery. In this review, we comprehensively surveyed the prospective applications of molecular docking judged by solid experimental validations in the literature over the past fifteen years. Herein, we systematically analyzed the novelty of the targets and the docking hits, practical protocols of docking screening, and the following experimental validations. Among the 419 case studies we reviewed, most virtual screenings were carried out on widely studied targets, and only 22% were on less-explored new targets. Regarding docking software, GLIDE is the most popular one used in molecular docking, while the DOCK 3 series showed a strong capacity for large-scale virtual screening. Besides, the majority of identified hits are promising in structural novelty and one-quarter of the hits showed better potency than 1 µM, indicating that the primary advantage of SBVS is to discover new chemotypes rather than highly potent compounds. Furthermore, in most studies, only in vitro bioassays were carried out to validate the docking hits, which might limit the further characterization and development of the identified active compounds. Finally, several successful stories of SBVS with extensive experimental validations have been highlighted, which provide unique insights into future SBVS drug discovery campaigns.

In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury.

COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by network pharmacology and bioinformatics methods. The combination of the protein-protein interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment -target gene network revealed eight key target genes (VEGFA, ICAM1, IL6, CXCL8, IL1B, CCL2, IL10 and RELA). Molecular docking showed that all these eight gene-encoded proteins could be effectively bound to three major active compounds (quercetin, luteolin and kaempferol), thus becoming potential therapeutic targets. Molecular dynamics simulation also supports the binding stability of RELA-encoded protein with quercetin and luteolin. Together, our data suggest that IL6, VEGFA, and RELA could be the potential drug targets by inhibiting the NF-κB signaling pathway. Our in silico studies shed new insights into P. vulgaris and its ingredients, e.g., quercetin, as potential botanical drugs against COVID-19 AKI, and warrant further studies on efficacy and mechanisms.

The anti-SARS-CoV-2 activity of novel 9, 10-dihydrophenanthrene derivatives: an insight into molecular docking, ADMET analysis, and molecular dynamics simulation.

Originating in Wuhan, the COVID-19 pandemic wave has had a profound impact on the global healthcare system. In this study, we used a 2D QSAR technique, ADMET analysis, molecular docking, and dynamic simulations to sort and evaluate the performance of thirty-nine bioactive analogues of 9,10-dihydrophenanthrene. The primary goal of the study is to use computational approaches to create a greater variety of structural references for the creation of more potent SARS-CoV-2 3Clpro inhibitors. This strategy is to speed up the process of finding active chemicals. Molecular descriptors were calculated using 'PaDEL' and 'ChemDes' software, and then redundant and non-significant descriptors were eliminated by a module in 'QSARINS ver. 2.2.2'. Subsequently, two statistically robust QSAR models were developed by applying multiple linear regression (MLR) methods. The correlation coefficients obtained by the two models are 0.89 and 0.82, respectively. These models were then subjected to internal and external validation tests, Y-randomization, and applicability domain analysis. The best model developed is applied to designate new molecules with good inhibitory activity values against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). We also examined various pharmacokinetic properties using ADMET analysis. Then, through molecular docking simulations, we used the crystal structure of the main protease of SARS-CoV-2 (3CLpro/Mpro) in a complex with the covalent inhibitor "Narlaprevir" (PDB ID: 7JYC). We also supported our molecular docking predictions with an extended molecular dynamics simulation of a docked ligand-protein complex. We hope that the results obtained in this study can be used as good anti-SARS-CoV-2 inhibitors.