Turkish journal of biology = Turk biyoloji dergisi最新文献

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The current state of validated small molecules inhibiting SARS-CoV-2 nonstructural proteins. 经验证的抑制SARS-CoV-2非结构蛋白小分子的现状。
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2106-42
Fatih Kocabaş, Merve Uslu
{"title":"The current state of validated small molecules inhibiting SARS-CoV-2 nonstructural proteins.","authors":"Fatih Kocabaş,&nbsp;Merve Uslu","doi":"10.3906/biy-2106-42","DOIUrl":"10.3906/biy-2106-42","url":null,"abstract":"<p><p>The current COVID-19 outbreak has had a profound influence on public health and daily life. Despite all restrictions and vaccination programs, COVID-19 still can lead to fatality due to a lack of COVID-19-specific treatments. A number of studies have demonstrated the feasibility to develop therapeutics by targeting underlying components of the viral proteome. Here we reviewed recently developed and validated small molecule inhibitors of SARS-CoV-2's nonstructural proteins. We described the validation level of identified compounds specific for SARS-CoV-2 in the presence of in vitro and in vivo supporting data. The mechanisms of pharmacological activity, as well as approaches for developing improved SARS-CoV-2 NSP inhibitors have been emphasized.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"469-483"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39643398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Determination of the interaction between the receptor binding domain of 2019-nCoV spike protein, TMPRSS2, cathepsin B and cathepsin L, and glycosidic and aglycon forms of some flavonols. 确定 2019-nCoV 穗状病毒蛋白、TMPRSS2、酪蛋白酶 B 和酪蛋白酶 L 的受体结合域与某些黄酮醇的糖苷和苷元形式之间的相互作用。
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2104-51
Erman Salih Istifli, Arzuhan Şihoğlu Tepe, Paulo A Netz, Cengiz Sarikürkcü, İbrahim Halil Kiliç, Bektaş Tepe
{"title":"Determination of the interaction between the receptor binding domain of 2019-nCoV spike protein, TMPRSS2, cathepsin B and cathepsin L, and glycosidic and aglycon forms of some flavonols.","authors":"Erman Salih Istifli, Arzuhan Şihoğlu Tepe, Paulo A Netz, Cengiz Sarikürkcü, İbrahim Halil Kiliç, Bektaş Tepe","doi":"10.3906/biy-2104-51","DOIUrl":"10.3906/biy-2104-51","url":null,"abstract":"<p><p>The novel coronavirus (COVID-19, SARS-CoV-2) is a rapidly spreading disease with a high mortality. In this research, the interactions between specific flavonols and the 2019-nCoV receptor binding domain (RBD), transmembrane protease, serine 2 (TMPRSS2), and cathepsins (CatB and CatL) were analyzed. According to the relative binding capacity index (RBCI) calculated based on the free energy of binding and calculated inhibition constants, it was determined that robinin (ROB) and gossypetin (GOS) were the most effective flavonols on all targets. While the binding free energy of ROB with the spike glycoprotein RBD, TMPRSS2, CatB, and CatL were -5.02, -7.57, -10.10, and -6.11 kcal/mol, the values for GOS were -4.67, -5.24, -8.31, and -6.76, respectively. Furthermore, both compounds maintained their stability for at least 170 ns on respective targets in molecular dynamics simulations. The molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations also corroborated these data. Considering Lipinski's rule of five, ROB and GOS exhibited 3 (MW>500, N or O>10, NH or OH>5), and 1 (NH or OH>5) violations, respectively. Neither ROB nor GOS showed AMES toxicity or hepatotoxicity. The LD50 of these compounds in rats were 2.482 and 2.527 mol/kg, respectively. Therefore, we conclude that these compounds could be considered as alternative therapeutic agents in the treatment of COVID-19. However, the possible inhibitory effects of these compounds on cytochromes (CYPs) should be verified by in vitro or in vivo tests and their adverse effects on cellular energy metabolism should be minimized by performing molecular modifications if necessary.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"484-502"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of weekend curfews on epidemics: a Monte Carlo simulation. 周末宵禁对流行病的影响:蒙特卡罗模拟。
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2105-69
Hakan Kaygusuz, A Nihat Berker
{"title":"The effect of weekend curfews on epidemics: a Monte Carlo simulation.","authors":"Hakan Kaygusuz, A Nihat Berker","doi":"10.3906/biy-2105-69","DOIUrl":"10.3906/biy-2105-69","url":null,"abstract":"<p><p>The ongoing COVID-19 pandemic is being responded with various methods, applying vaccines, experimental treatment options, total lockdowns or partial curfews. Weekend curfews are among the methods for reducing the number of infected persons, and this method is practically applied in some countries such as Turkey. In this study, the effect of weekend curfews on reducing the spread of a contagious disease, such as COVID-19, is modeled using a Monte Carlo algorithm with a hybrid lattice model. In the simulation setup, a fictional country with three towns and 26,610 citizens were used as a model. Results indicate that applying a weekend curfew reduces the ratio of ill cases from 0.23 to 0.15. The results also show that applying personal precautions such as social distancing is important for reducing the number of cases and deaths. If the probability of disease spread can be reduced to 0.1, in that case, the death ratio can be minimized down to 0.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"436-441"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39643395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An update comprehensive review on the status of COVID-19: vaccines, drugs, variants and neurological symptoms. 关于COVID-19现状的最新综合综述:疫苗、药物、变体和神经系统症状。
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2106-23
Ebru Özkan Oktay, Salih Tuncay, Tuğba Kaman, Ömer Faruk Karasakal, Öznur Özge Özcan, Tuğçe Soylamiş, Mesut Karahan, Muhsin Konuk
{"title":"An update comprehensive review on the status of COVID-19: vaccines, drugs, variants and neurological symptoms.","authors":"Ebru Özkan Oktay,&nbsp;Salih Tuncay,&nbsp;Tuğba Kaman,&nbsp;Ömer Faruk Karasakal,&nbsp;Öznur Özge Özcan,&nbsp;Tuğçe Soylamiş,&nbsp;Mesut Karahan,&nbsp;Muhsin Konuk","doi":"10.3906/biy-2106-23","DOIUrl":"10.3906/biy-2106-23","url":null,"abstract":"<p><p>Various recently reported mutant variants, candidate and urgently approved current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many current situations with severe neurological damage and symptoms as well as respiratory tract disorders have begun to be reported. In particular, drug, vaccine, and neutralizing monoclonal antibodies (mAbs) have been developed and are currently being evaluated in clinical trials. Here, we review lessons learned from the use of novel mutant variants of the COVID-19 virus, immunization, new drug solutions, and antibody therapies for infections. Next, we focus on the B 1.1.7, B 1.351, P.1, and B.1.617 lineages or variants of concern that have been reported worldwide, the new manifestations of neurological manifestations, the current therapeutic drug targets for its treatment, vaccine candidates and their efficacy, implantation of convalescent plasma, and neutralization of mAbs. We review specific clinical questions, including many emerging neurological effects and respiratory tract injuries, as well as new potential biomarkers, new studies in addition to known therapeutics, and chronic diseases of vaccines that have received immediate approval. To answer these questions, further understanding of the burden kinetics of COVID-19 and its correlation with neurological clinical outcomes, endogenous antibody responses to vaccines, pharmacokinetics of neutralizing mAbs, and action against emerging viral mutant variants is needed.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"342-357"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39642929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Targeting CoV-2 spike RBD and ACE-2 interaction with flavonoids of Anatolian propolis by in silico and in vitro studies in terms of possible COVID-19 therapeutics. 针对CoV-2刺突RBD和ACE-2与安纳托利亚蜂胶类黄酮相互作用的新冠肺炎治疗方法的硅和体外研究
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2104-5
Halil İbrahim Güler, Fulya Ay Şal, Zehra Can, Yakup Kara, Oktay Yildiz, Ali Osman Beldüz, Sabriye Çanakçi, Sevgi Kolayli
{"title":"Targeting CoV-2 spike RBD and ACE-2 interaction with flavonoids of Anatolian propolis by in silico and in vitro studies in terms of possible COVID-19 therapeutics.","authors":"Halil İbrahim Güler,&nbsp;Fulya Ay Şal,&nbsp;Zehra Can,&nbsp;Yakup Kara,&nbsp;Oktay Yildiz,&nbsp;Ali Osman Beldüz,&nbsp;Sabriye Çanakçi,&nbsp;Sevgi Kolayli","doi":"10.3906/biy-2104-5","DOIUrl":"10.3906/biy-2104-5","url":null,"abstract":"<p><p>Propolis is a multi-functional bee product rich in polyphenols. In this study, the inhibitory effect of Anatolian propolis against SARS-coronavirus-2 (SARS-CoV-2) was investigated in vitro and in silico. Raw and commercial propolis samples were used, and both samples were found to be rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin, and caffeic acid phenethyl ester (CAPE) at HPLC-UV analysis. Ethanolic propolis extracts (EPE) were used in the ELISA screening test against the spike S1 protein (SARS-CoV-2): ACE-2 interaction for in vitro study. The binding energy values of these polyphenols to the SARS-CoV-2 spike and ACE-2 protein were calculated separately with a molecular docking study using the AutoDock 4.2.6 program. In addition, the pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. The binding energy value of pinocembrin was highest in both receptors, followed by chrysin, CAPE, and hesperetin. Based on the in silico modeling and ADME (absorption, distribution, metabolism, and excretion) behaviors of the eight polyphenols, the compounds exhibited the potential ability to act effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against the Covid-19 virus. However, further studies are now needed.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"530-548"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 22
CoronaVac (Sinovac) COVID-19 vaccine-induced molecular changes in healthy human serum by infrared spectroscopy coupled with chemometrics. 新冠肺炎疫苗诱导健康人血清分子变化的红外光谱联合化学计量学研究
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2105-65
Ayca Dogan, Rafig Gurbanov, Mete Severcan, Feride Severcan
{"title":"CoronaVac (Sinovac) COVID-19 vaccine-induced molecular changes in healthy human serum by infrared spectroscopy coupled with chemometrics.","authors":"Ayca Dogan,&nbsp;Rafig Gurbanov,&nbsp;Mete Severcan,&nbsp;Feride Severcan","doi":"10.3906/biy-2105-65","DOIUrl":"https://doi.org/10.3906/biy-2105-65","url":null,"abstract":"<p><p>From the beginning of the COVID-19 coronavirus pandemic in December of 2019, the disease has infected millions of people worldwide and caused hundreds of thousands of deaths. Since then, several vaccines have been developed. One of those vaccines is inactivated CoronaVac-Sinovac COVID-19 vaccine. In this proof of concept study, we first aimed to determine CoronaVac-induced biomolecular changes in healthy human serum using infrared spectroscopy. Our second aim was to see whether the vaccinated group can be separated or not from the non-vaccinated group by applying chemometric techniques to spectral data. The results revealed that the vaccine administration induced significant changes in some functional groups belonging to lipids, proteins and nucleic acids. In addition, the non-vaccinated and vaccinated groups were successfully separated from each other by principal component analysis (PCA) and linear discriminant analysis (LDA). This proof-of-concept study will encourage future studies on CoronaVac as well as other vaccines and will lead to make a comparison between different vaccines to establish a better understanding of the vaccination outcomes on serum biomolecules.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"549-558"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
The potential use of Drosophila as an in vivo model organism for COVID-19-related research: a review. 果蝇作为体内模型生物在covid -19相关研究中的潜在应用综述
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2104-26
Eşref Demir
{"title":"The potential use of <i>Drosophila</i> as an in vivo model organism for COVID-19-related research: a review.","authors":"Eşref Demir","doi":"10.3906/biy-2104-26","DOIUrl":"https://doi.org/10.3906/biy-2104-26","url":null,"abstract":"<p><p>The world urgently needs effective antiviral approaches against emerging viruses, as shown by the coronavirus disease 2019 (COVID-19) pandemic, which has become an exponentially growing health crisis. Scientists from diverse backgrounds have directed their efforts towards identifying key features of SARS-CoV-2 and clinical manifestations of COVID-19 infection. Reports of more transmissible variants of SARS-CoV-2 also raise concerns over the possibility of an explosive trajectory of the pandemic, so scientific attention should focus on developing new weapons to help win the fight against coronaviruses that may undergo further mutations in the future. <i>Drosophila melanogaster</i> offers a powerful and potential in vivo model that can significantly increase the efficiency of drug screening for viral and bacterial infections. Thanks to its genes with functional human homologs, <i>Drosophila</i> could play a significant role in such gene-editing studies geared towards designing vaccines and antiviral drugs for COVID-19. It can also help rectify current drawbacks of CRISPR-based therapeutics like off-target effects and delivery issues, representing another momentous step forward in healthcare. Here I present an overview of recent literature and the current state of knowledge, explaining how it can open up new avenues for <i>Drosophila</i> in our battle against infectious diseases.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"559-569"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Pathogenesis and treatment of cytokine storm in COVID-19. COVID-19细胞因子风暴的发病机制及治疗。
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2105-37
Mehmet Soy, Gökhan Keser, Pamir Atagündüz
{"title":"Pathogenesis and treatment of cytokine storm in COVID-19.","authors":"Mehmet Soy,&nbsp;Gökhan Keser,&nbsp;Pamir Atagündüz","doi":"10.3906/biy-2105-37","DOIUrl":"https://doi.org/10.3906/biy-2105-37","url":null,"abstract":"<p><p>COVID-19 is a viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that killed a large number of patients around the world. A hyperinflammatory state resulting in a cytokine storm and adult respiratory distress syndrome seems to be the major cause of the death. Many mechanisms have been suggested in the pathogenesis of COVID-19 associated cytokine storm (COVID-CS). Insufficient viral clearance and persistence of a strong cytokine response despite inadequate antiviral immunity seem to be the main mechanisms underlying the pathogenesis. The diagnosis of COVID-19 is based on relatively constant clinical symptoms, clinical findings, laboratory tests, and imaging techniques, while the diagnosis of COVID-CS is a rather dynamic process, based on evolving or newly emerging findings during the clinical course. Management of COVID-19 consists of using antiviral agents to inhibit SARS-CoV-2 replication and treating potential complications including the cytokine storm together with general supportive measures. COVID-CS may be treated using appropriate immunosuppressive and immunomodulatory drugs that reduce the level of inappropriate systemic inflammation, which has the potential to cause organ damage. Currently corticosteroids, IL-6 blockers, or IL-1 blockers are most widely used for treating COVID-CS.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"372-389"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39643391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Genomic chronicle of SARS-CoV-2: a mutational analysis with over 1 million genome sequences. SARS-CoV-2的基因组编年史:超过100万个基因组序列的突变分析
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2106-8
Osman Mutluhan Uğurel, Oğuz Ata, Dilek Turgut-Balik
{"title":"Genomic chronicle of SARS-CoV-2: a mutational analysis with over 1 million genome sequences.","authors":"Osman Mutluhan Uğurel,&nbsp;Oğuz Ata,&nbsp;Dilek Turgut-Balik","doi":"10.3906/biy-2106-8","DOIUrl":"10.3906/biy-2106-8","url":null,"abstract":"<p><p>Use of information technologies to analyse big data on SARS-CoV-2 genome provides an insight for tracking variations and examining the evolution of the virus. Nevertheless, storing, processing, alignment and analyses of these numerous genomes are still a challenge. In this study, over 1 million SARS-CoV-2 genomes have been analysed to show distribution and relationship of variations that could enlighten development and evolution of the virus. In all genomes analysed in this study, a total of over 215M SNVs have been detected and average number of SNV per isolate was found to be 21.83. Single nucleotide variant (SNV) average is observed to reach 31.25 just in March 2021. The average variation number of isolates is increasing and compromising with total case numbers around the world. Remarkably, cytosine deamination, which is one of the most important biochemical processes in the evolutionary development of coronaviruses, accounts for 46% of all SNVs seen in SARS-CoV-2 genomes within 16 months. This study is one of the most comprehensive SARS-CoV-2 genomic analysis study in terms of number of genomes analysed in an academic publication so far, and reported results could be useful in monitoring the development of SARS-CoV-2.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"425-435"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39643393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
β-Carboline alkaloids induce structural plasticity and inhibition of SARS-CoV-2 nsp3 macrodomain more potently than remdesivir metabolite GS-441524: computational approach. β-咔啉生物碱诱导结构可塑性和抑制SARS-CoV-2 nsp3大域的作用比雷米替韦代谢物GS-441524更强:计算方法。
Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-08-30 eCollection Date: 2021-01-01 DOI: 10.3906/biy-2106-64
Yusuf Oloruntoyin Ayipo, Sani Najib Yahaya, Halimah Funmilayo Babamale, Iqrar Ahmad, Harun Patel, Mohd Nizam Mordi
{"title":"β-Carboline alkaloids induce structural plasticity and inhibition of SARS-CoV-2 nsp3 macrodomain more potently than remdesivir metabolite GS-441524: computational approach.","authors":"Yusuf Oloruntoyin Ayipo, Sani Najib Yahaya, Halimah Funmilayo Babamale, Iqrar Ahmad, Harun Patel, Mohd Nizam Mordi","doi":"10.3906/biy-2106-64","DOIUrl":"10.3906/biy-2106-64","url":null,"abstract":"<p><p>The nsp3 macrodomain is implicated in the viral replication, pathogenesis and host immune responses through the removal of ADP-ribosylation sites during infections of coronaviruses including the SARS-CoV-2. It has ever been modulated by macromolecules including the ADP-ribose until Ni and co-workers recently reported its inhibition and plasticity enhancement unprecedentedly by <b>remdesivir</b> metabolite, <b>GS-441524</b>, creating an opportunity for investigating other biodiverse small molecules such as β-Carboline (βC) alkaloids. In this study, 1497 βC analogues from the HiT2LEAD chemical database were screened, using computational approaches of Glide XP docking, molecular dynamics simulation and pk-CSM ADMET predictions. Selectively, βC ligands, <b>129, 584</b>, <b>1303</b> and <b>1323</b> demonstrated higher binding affinities to the receptor, indicated by XP docking scores of -10.72, -10.01, -9.63 and -9.48 kcal/mol respectively than <b>remdesivir</b> and <b>GS-441524</b> with -4.68 and -9.41 kcal/mol respectively. Consistently, their binding free energies were -36.07, -23.77, -24.07 and -17.76 kcal/mol respectively, while <b>remdesivir</b> and <b>GS-441524</b> showed -21.22 and -24.20 kcal/mol respectively. Interestingly, the selected βC ligands displayed better stability and flexibility for enhancing the plasticity of the receptor than <b>GS-441524</b>, especially <b>129</b> and <b>1303</b>. Their predicted ADMET parameters favour druggability and low expressions for toxicity. Thus, they are recommended as promising adjuvant/standalone anti-SARS-CoV-2 candidates for further study.<b>Key words</b>: SARS-CoV-2, nsp3 macrodomain, ADP-ribose, β-carboline, bioinformatics, drug design.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"503-517"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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