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Objective. Most respiratory infections have similar symptoms, so it is clinically difficult to determine their etiology. This study aimed to show the importance of molecular diagnostics in identifying the etiological agent of respiratory infections, especially during the coronavirus disease 2019 (COVID-19) pandemic. Methods. A total of 849 samples from patients hospitalized at the University Clinical Center Kragujevac (from January 1 to August 1, 2022) were examined using automated multiplex-polymerase chain reaction (PCR) tests. The BioFire-FilmArray-Respiratory Panel 2.1 test was used for 742 nasopharyngeal swabs [identification of 19 viruses (including SARS-CoV-2) and four bacteria], while the BioFire-FilmArray-Pneumonia Panel was used [identification of 18 bacteria and nine viruses] (BioMerieux, Marcy l'Etoile, France) for 107 tracheal aspirates. The tests were performed according to the manufacturer's instructions, and the results were available within an hour. Results. In 582 (78.4%) samples, the BioFire-FilmArray-Respiratory Panel 2.1 plus test identified at least one pathogen. The rhinovirus (20.6%), SARS-CoV-2 (17.7%), influenza A (17.5%), respiratory syncytial virus (12.4%), and parainfluenza 3 (10.1%) were the most common. Other viruses were found less frequently, and Bordetella parapertussis was detected in one sample. In 85 (79.4%) samples, the BioFire-FilmArray-Pneumonia Panel test identified at least one bacterium or virus. The most prevalent bacteria were Staphylococcus aureus (42.4%), Haemophilus influenzae (41.2%), Streptococcus pneumoniae (36.5%), Moraxella catarrhalis (22.3%), and Legionella pneumophila (2.4%). Among viruses, rhinovirus (36.5%), adenovirus (23.5%), influenza A (11.8%), and the genus Coronavirus (4.7%), were detected. Conclusion. Multiplex-PCR tests improved the implementation of therapeutic and epidemiological measures, preventing the spread of the COVID-19 infection and Legionnaires' disease.Copyright © 2022, Serbian Medical Society. All rights reserved.
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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.
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Objectives: The aim of this study was to assess Jordanian physicians' awareness about venous thromboembolism (VTE) risk among COVID-19 patients and its treatment protocol. Method(s): This was a cross-sectional-based survey that was conducted in Jordan in 2020. During the study period, a convenience sample of physicians working in various Jordanian hospitals were invited to participate in this study. Physicians' knowledge was evaluated and physicians gained one point for each correct answer. Then, a knowledge score out of 23 was calculated for each. Key Findings: In this study, 102 physicians were recruited. Results from this study showed that most of the physicians realize that all COVID-19 patients need VTE risk assessment (n = 69, 67.6%). Regarding VTE prophylaxis, the majority of physicians (n = 91, 89.2%) agreed that low molecular weight heparin (LMWH) is the best prophylactic option for mild-moderate COVID-19 patients with high VTE risk. Regarding severe/critically ill COVID-19 patients, 75.5% of physicians (n = 77) recognized that LMWH is the correct prophylactic option in this case, while 80.4% of them (n = 82) knew that mechanical prevention is the preferred prophylactic option for severe/critically ill COVID-19 patients with high bleeding risk. Moreover, 77.5% of physicians (n = 79) knew that LMWH is the treatment of choice for COVID-19 patients diagnosed with VTE. Finally, linear regression analysis showed that consultants had an overall higher knowledge score about VTE prevention and treatment in COVID-19 patients compared with residents (P = 0.009). Conclusion(s): All physicians knew about VTE risk factors for COVID-19 patients. However, consultants showed better awareness of VTE prophylaxis and treatment compared with residents. We recommend educational workshops be conducted to enhance physicians' knowledge and awareness about VTE thromboprophylaxis and management in COVID-19 patients.Copyright © 2022 The Author(s). Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved.
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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.
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Severe pneumonia is a condition with a high risk of death and mandatory hospitalization in the intensive care unit. The incidence of severe pneumonia has increased dramatically during the pandemic of new coronavirus infection. Timely diagnosis and early initiation of adequate treatment of severe pneumonia are crucial for improving survival of critically ill patients. The aim of this review was to analyze published scientific research on molecular markers that allow to objectively assess the severity of pneumonia and to determine treatment tactics based on the predicted outcome upon admission to the hospital. A systematic search was conducted in the electronic databases PubMed, Medline, Web of Science for the period 2019 - 2022. Conclusion. The review focuses on the prognostic role of a number of markers of immune response, vascular transformation, as well as angiotensin II and angiotensin converting enzyme-2. Further prospective studies of potential predictors of severe pneumonia will enable using marker molecules in a comprehensive clinical and laboratory diagnosis for early prediction of the hospitalized patient's condition and expected outcome.Copyright © Volchkova E.V. et al., 2023.
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Introduction: One in five pregnant women in the UKis obese. Obesity is associated with increased risk of both maternal and foetal adverse outcomes. RCOG guidelines [1] recommend that all women with a booking BMI over 40 kg/m2 should be reviewed antenatally by a senior obstetric anaesthetist to guide risk assessment, medical optimisation and shared decision-making. The 2021 MBRRACE report [2] recommends that all women should be reweighed in the third trimester for accurate VTE risk scoring and prophylactic LMWH dosing. In our institution, reconfiguration of hospital areas as part of the COVID-19 response led to loss of designated clinic space for our obstetric anaesthetic clinic. As a result, our practice since has been to initially offer a telephone consultation followed by a face-to-face review if needed. Finding space for the latter has often been a significant logistical challenge. Our project sought to assess whether our practice continued to meet national standards in the wake of these changes. Method(s): Following audit approval, we retrospectively reviewed all women with a BMI >40 kg/m2 undergoing caesarean section (CS) over a six-month period (1/4/22 to 31/9/22). Result(s): 20 women met inclusion criteria (Category 1-3 CS - 12 women;Category 4 CS - 8 women). 100% of patients had booking height, weight and BMI recorded. 20% (4/20) of patients were reweighed in the 3rd trimester. Only 55% (11/20) of patients had been referred to and reviewed in the antenatal obstetric anaesthetic clinic (Figure). Of the 11 patients referred, 6 were referred later than 30 weeks. Of the 9 patients not referred, 8 had a BMI between 40 and 45 kg/m2. By contrast, 87% (6/7) of patients with BMI over 45 kg/m2 were referred and seen. Discussion(s): Our audit showed that we are not meeting national standards. Possible reasons identified were lack of awareness of the RCOG standards and referral criteria (especially for women with a BMI of 40 to 45 kg/m2) and logistical issues in undertaking face-to-face reviews without designated clinic space. Presentation of our results at the joint anaesthetic, obstetric and midwifery governance meeting has helped identify space in the antenatal clinic for face-to-face reviews, to start from March 2023 and to raise awareness of the national standards to ensure referral of all women with a BMI over 40 kg/m2. A reaudit is planned in 6 months. [Figure presented]Copyright © 2023 Elsevier Ltd
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Summary Introduction: The SARS-CoV-2 coronavirus, that causes the COVID-19 disease, has become a global public health problem that requires the implementation of rapid and sensitive diagnostic tests. Aim(s): To evaluate and compare the sensitivity of LAMP assay to a standard method and use RT-LAMP for the diagnosis of SARS-CoV-2 in clinical samples from Colombian patients. Method(s): A descriptive and cross-sectional study was conducted. A total of 25 nasopharyngeal swab samples including negative and positive samples for SARS-CoV-2 were analyzed, through the RT-LAMP method compared to the RT-qPCR assay. Result(s): LAMP method detected ~18 copies of the N gene, in 30 min, evidenced a detection limit similar to the standard method, in a shorter time and a concordance in RT-LAMP of 100% with the results. Conclusion(s): RT-LAMP is a sensitive, specific, and rapid method that can be used as a diagnostic aid of COVID-19 disease.Copyright © 2021. All Rights Reserved.
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The aim of this study was to evaluate the impact of the most frequent Asn501 polar uncharged amino acid mutations upon important structural properties of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Surface Glycoprotein RBD–hACE2 (human angiotensin-converting enzyme 2) heterodimer. Mutations N501Y, N501T and N501S were considered and their impact upon complex solubility, secondary motifs formation and intermolecular hydrogen bonding interface was analyzed. Results and findings are reported based on 50 ns run in Gromacs molecular dynamics simulation software. Special attention is paid on the biomechanical shifts in the receptor-binding domain (RBD) [499-505]: ProThrAsn(Tyr)GlyValGlyTyr, having substituted Asparagine to Tyrosine at position 501. The main findings indicate that the N501S mutation increases SARS-CoV-2 S-protein RBD–hACE2 solubility over N501T, N501 (wild type): (Formula presented.), (Formula presented.). The N501Y mutation shifts (Formula presented.) -helix S-protein RBD [366-370]: SerValLeuTyrAsn into π-helix for t > 38.5 ns. An S-protein RBD [503-505]: ValGlyTyr shift from (Formula presented.) -helix into a turn is observed due to the N501Y mutation in t > 33 ns. An empirical proof for the presence of a Y501-binding pocket, based on RBD [499-505]: PTYGVGY (Formula presented.) 's RMSF peak formation is presented. There is enhanced electrostatic interaction between Tyr505 (RBD) phenolic -OH group and Glu37 (hACE2) side chain oxygen atoms due to the N501Y mutation. The N501Y mutation shifts the (Formula presented.) hydrogen bond into permanent polar contact;(Formula presented.);(Formula presented.). © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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Over the past century, synthetic polymers have had a transformative impact on human life, replacing nature-derived materials in many areas. Yet, despite their many advantages, the structure and function of synthetic polymers still appear rudimentary compared to biological matter: cells use dynamic self-assembly to construct complex materials and operate sophisticated macromolecular devices. The field of DNA nanotechnology has demonstrated that synthetic DNA molecules can be programmed to undergo predictable self-assembly, offering unparalleled control over the formation and dynamic properties of artificial nanostructures. Intriguingly, the principles of DNA nanotechnology can be applied to the engineering of soft programmable materials, bringing the abilities of synthetic polymers closer to their biological counterparts. In this perspective, we discuss the unique features of DNA-functionalized polymer materials. We describe design principles that allow researchers to build complex supramolecular architectures with predictable and dynamically adjustable material properties. Finally, we highlight two key application areas where this biologically inspired material class offers particularly promising opportunities: (1) as dynamic matrices for 3D cell and organoid culture and (2) as smart materials for nucleic acid sequencing and pathogen detection.
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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.
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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.
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Canine parvovirus (CPV), canine coronavirus (CCoV) and canine rotavirus (CRV) are the three main causative viruses of diarrhea in dogs with similar clinical symptoms;thereby it is necessary to establish a high effective molecular detection method for differentiating the above pathogens. By optimizing the primer concentration and annealing temperature, a triple PCR method was established for simultaneous detection of CPV, CCoV and CRV, and then the specificity, sensitivity and repeatability of the method were tested. The results showed that the target fragments of CPV VP2 gene (253 bp), CCoV ORF-1b gene (379 bp) and CRV VP6 gene (852 bp) could be accurately amplified by the triple PCR method with high specificity, the detection limits of CPV, CCOV and CRV were 6.44x10-1 pg/L, 8.72x10-1 pg/L and 8.35x10-1 pg/L respectively with high sensitivity, and the method had good stability. Using this triple PCR method, 135 canine diarrhea fecal samples collected in Chengdu region from 2019 to 2020 were detected, and compared with those of single PCR method. The detection rates of CPV, CCoV and CRV were 16.30%, 20.74% and 4.44%, respectively, and the total infection rate was 51.11% (65/135) with 20.00% (13/65) co-infection rate. The detection results were consistent with three single PCR methods. In conclusion, CPV/CCoV/CRV triple PCR method successfully established in this paper can be applied as an effective molecular method to detection of related pathogens and to the epidemiological investigation.
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During the COVID-19 pandemic, point-of-care genetic testing (POCT) devices were used for on-time and on-site detection of the virus, which helped to prevent and control the spread of the pandemic. Smartphones, which are widely used electronic devices with many functions, have the potential to be used as a molecular diagnostic platform for universal healthcare monitoring. Several integrated diagnostics platforms for the real-time and end-point detection of COVID-19 were developed using the functions of smartphones, such as the operating system, power, sound, camera, data storage, and display. These platforms use the 5V output power of smartphones, which can be amplified to power a micro-capillary electrophoresis system or a thin-film heater, and the CMOS camera of smartphones can capture the color change during a colorimetric loop-mediated isothermal amplification test and detect fluorescence signals. Smartphones can also be used with self-written web-based apps to enable automatic and remote pathogen analysis on POCT platforms. Our lab developed a handheld micro-capillary electrophoresis device for end-point detection of SARS-CoV-2, as well as an integrated smartphone-based genetic analyzer for the qualitative and quantitative colorimetric detection of foodborne pathogens with the help of a custom mobile app. © 2023 SPIE.
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The non-orthogonal local submatrix method applied to electronic structure–based molecular dynamics simulations is shown to exceed 1.1 EFLOP/s in FP16/FP32-mixed floating-point arithmetic when using 4400 NVIDIA A100 GPUs of the Perlmutter system. This is enabled by a modification of the original method that pushes the sustained fraction of the peak performance to about 80%. Example calculations are performed for SARS-CoV-2 spike proteins with up to 83 million atoms. [ FROM AUTHOR] Copyright of International Journal of High Performance Computing Applications is the property of Sage Publications, Ltd. 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.)
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This work sheds light on the effect of boswellic acid compounds (Alpha boswellic acid, Beta boswellic acid, 11-keto beta boswellic acid and 3-Acetyl-11-keto beta boswellic acid) upon inhibiting SARS-CoV-2 M-pro and O-M-pro (Main protease). A good docking score (-8.4 kcal/mol) is found in the case of 3-Acetyl-11-keto beta boswellic acid as compared to the reference and three other boswellic acid compounds. ADMET results suggest that all these compounds are nontoxic and their pharmacokinetic properties are satisfactory. Moreover, a stability analysis with M-pro/O-M-pro through RMSD, RMSF, hydrogen bonds and Rg parameters in MD simulations is made and we found better values than the reference case. Pre and post-MD structures of Ligands-M-pro show a similar binding site whereas a drift can be noted for L-O-M-pro. 3-Acetyl-11-keto beta boswellic acid shows an average of five hydrogen bonds and it remains stable within the binding pocket of M-pro during the simulation period in comparison to other boswellic acids compounds. Various metastable conformations are observed for all compounds in FEL (free energy landscape), however, Acyclovir-M-pro, Alpha boswellic acid-M-pro and Beta boswellic acid-O-M-pro display only one global minimum. The results suggest that these compounds can be used as potential lead molecules for breakthroughs in drug discovery.
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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.
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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.
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In the last 20 years, the world has been threatened with coronavirus (CoV) pandemic threats from severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 and finally COVID-19 due to SARS-CoV-2 in 2019. These viruses posed serious global pandemic threats, with estimated case fatality rates of 15% for SARS-CoV, 34% for MERS-CoV, and 1-3% for SARS-CoV-2. With the current pandemic still far from over there is an urgent need to find new drug treatments for COVID-19. We can assume that this will not be the last coronavirus to threaten humanity, so we need better tools to identify drugs active against past but also future coronavirus threats. In this Chapter we describe in silico computer modeling and screening approaches that can rapidly identify drugs from existing drug libraries that could be repurposed to treat COVID-19 infections. We also describe how this computational screening pipeline can be expanded in the future to identify drugs with broad spectrum activity against a wide diversity of coronaviruses. A significant concern is that the protection against CoVs provided by single drugs protection may be short-lived because viruses rapidly mutate to develop drug resistance. We know from other viruses such as HIV that drugs hitting multiple targets within the virus provide better protection against the development of resistance. This Chapter describes the current state of development of in silico CoV drug repurposing, the challenges and pitfalls of these approaches, and our predictions of how these methods could be used to develop drugs for future pandemics before they occur. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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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).
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Chemical graph theory is currently expanding the use of topological indices to numerically encode chemical structure. The prediction of the characteristics provided by the chemical structure of the molecule is a key feature of these topological indices. The concepts from graph theory are presented in a brief discussion of one of its many applications to chemistry, namely, the use of topological indices in quantitative structure-activity relationship (QSAR) studies and quantitative structure-property relationship (QSPR) studies. This study uses the M-polynomial approach, a newly discovered technique, to determine the topological indices of the medication fenofibrate. With the use of degree-based topological indices, we additionally construct a few novel degree based topological descriptors of fenofibrate structure using M-polynomial. When using M-polynomials in place of degree-based indices, the computation of the topological indices can be completed relatively quickly. The topological indices are also plotted. Using M-polynomial, we compute novel formulas for the modified first Zagreb index, modified second Zagreb index, first and second hyper Zagreb indices, SK index, SK1 index, SK2 index, modified Albertson index, redefined first Zagreb index, and degree-based topological indices.