Zhibin Yan, Guangyu Zhao, Qihao Lin, Guiping Zhuang, Jiayi Zhu, Juan Jin
Abstract Carapax Trionycis is a traditional Chinese medicine and it has been clear that oligo‐peptides from Carapax Trionycis extract (CTP) are the main active substances for the treatment of liver diseases. However, little is known about the mechanism of CTP against liver fibrosis. Here, network pharmacology combined with molecular docking were performed to identify the in‐silico molecular mechanism and the potential targets for CTP to ameliorate liver fibrosis. We collected eight active peptides ingredients that published in public databases and predicted the targets. Liver fibrosis related genes were acquired from the GeneCards and DisGeNET platform. Then, we identified a total of 52 peptides‐liver fibrosis‐related genes. KEGG and GO enrichment analyses indicated that these targets are significantly enriched in relaxin signaling pathway, IL‐17 signaling pathway, TNF signaling pathway. We identified the top 10 genes with high centrality measures from the network by CytoHubba, including CASP3, AKT1, IL1B, MMP9, and PTGS2. The molecular docking between these hub genes and the corresponding CTP was performed in GRAMM and visualized by PyMOL. Our results provide an important reference and scientific basis for treating liver fibrosis with CTP.
{"title":"A network pharmacology approach to explore the molecular mechanism of active peptide ingredients of <i>Carapax Trionycis</i> on liver fibrosis","authors":"Zhibin Yan, Guangyu Zhao, Qihao Lin, Guiping Zhuang, Jiayi Zhu, Juan Jin","doi":"10.1002/pep2.24335","DOIUrl":"https://doi.org/10.1002/pep2.24335","url":null,"abstract":"Abstract Carapax Trionycis is a traditional Chinese medicine and it has been clear that oligo‐peptides from Carapax Trionycis extract (CTP) are the main active substances for the treatment of liver diseases. However, little is known about the mechanism of CTP against liver fibrosis. Here, network pharmacology combined with molecular docking were performed to identify the in‐silico molecular mechanism and the potential targets for CTP to ameliorate liver fibrosis. We collected eight active peptides ingredients that published in public databases and predicted the targets. Liver fibrosis related genes were acquired from the GeneCards and DisGeNET platform. Then, we identified a total of 52 peptides‐liver fibrosis‐related genes. KEGG and GO enrichment analyses indicated that these targets are significantly enriched in relaxin signaling pathway, IL‐17 signaling pathway, TNF signaling pathway. We identified the top 10 genes with high centrality measures from the network by CytoHubba, including CASP3, AKT1, IL1B, MMP9, and PTGS2. The molecular docking between these hub genes and the corresponding CTP was performed in GRAMM and visualized by PyMOL. Our results provide an important reference and scientific basis for treating liver fibrosis with CTP.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135779743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Azobenzenes are a series of compounds that can be isomerized upon irradiation with light. These molecules can modify the physical, chemical, and biological properties of a diverse range of materials. They can control protein structure and function with temporal and spatial precision. In this work, we investigated the possible interaction between azobenzene and aromatic amino acids. We hypothesized that aromatic amino acids, such as tryptophan, would show altered photochemical properties when conjugated with azobenzene. When irradiated at either 365 nm or 465 nm, the molecule now lacks the usually characteristic photoswitch capabilities and is visibly fluorescent at 365 nm. To our knowledge, this is the first evidence to suggest that primary protein structure could affect photoswitch activity. The knowledge gained from this research will help to further the understanding of azobenzenes as they are used in biomolecules.
{"title":"Investigating the interaction of azobenzene moiety on the aromatic amino acid tryptophan","authors":"Charnette Frederic, Gregory R. Wiedman","doi":"10.1002/pep2.24334","DOIUrl":"https://doi.org/10.1002/pep2.24334","url":null,"abstract":"Abstract Azobenzenes are a series of compounds that can be isomerized upon irradiation with light. These molecules can modify the physical, chemical, and biological properties of a diverse range of materials. They can control protein structure and function with temporal and spatial precision. In this work, we investigated the possible interaction between azobenzene and aromatic amino acids. We hypothesized that aromatic amino acids, such as tryptophan, would show altered photochemical properties when conjugated with azobenzene. When irradiated at either 365 nm or 465 nm, the molecule now lacks the usually characteristic photoswitch capabilities and is visibly fluorescent at 365 nm. To our knowledge, this is the first evidence to suggest that primary protein structure could affect photoswitch activity. The knowledge gained from this research will help to further the understanding of azobenzenes as they are used in biomolecules.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135855065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Bioactive peptides are currently emerging as nonpharmacological alternatives for treating noncommunicable diseases, including hypertension. Pharmacological treatments for hypertension typically involve angiotensin I converting enzyme inhibitors such as Captopril and enalapril. This study aimed to evaluate the activity of bioactive peptides derived from food sources against this enzyme and show its possible mechanism of inhibitory action. A comprehensive search was conducted in peptide databases to identify peptides with antihypertensive properties. Subsequently, docking studies, simulations, and predictive tests assessing ADME parameters, intestinal stability, and allergenicity were performed using bioinformatics tools. The docking and simulation results demonstrated that PEP2 exhibited superior ACE1 inhibitory potential compared to other peptides, even though it had lower human intestinal absorption. In conclusion, this study suggests that these peptides hold promising potential as nutraceuticals for hypertension treatment.
{"title":"Bioactive peptides against angiotensin‐converting enzyme I: An <scp><i>in silico</i></scp> study","authors":"Antistio Alvíz‐Amador, Neyder Contreras‐Puentes, Johana Márquez‐Lázaro","doi":"10.1002/pep2.24332","DOIUrl":"https://doi.org/10.1002/pep2.24332","url":null,"abstract":"Abstract Bioactive peptides are currently emerging as nonpharmacological alternatives for treating noncommunicable diseases, including hypertension. Pharmacological treatments for hypertension typically involve angiotensin I converting enzyme inhibitors such as Captopril and enalapril. This study aimed to evaluate the activity of bioactive peptides derived from food sources against this enzyme and show its possible mechanism of inhibitory action. A comprehensive search was conducted in peptide databases to identify peptides with antihypertensive properties. Subsequently, docking studies, simulations, and predictive tests assessing ADME parameters, intestinal stability, and allergenicity were performed using bioinformatics tools. The docking and simulation results demonstrated that PEP2 exhibited superior ACE1 inhibitory potential compared to other peptides, even though it had lower human intestinal absorption. In conclusion, this study suggests that these peptides hold promising potential as nutraceuticals for hypertension treatment.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135965982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam G. Kreutzer, Ryan J. Malonis, Chelsea Marie T. Parrocha, Karen Tong, Gretchen Guaglianone, Jennifer T. Nguyen, Michelle N. Diab, Jonathan R. Lai, James S. Nowick
Abstract Monoclonal antibodies (mAbs) that target the β‐amyloid peptide (Aβ) are important Alzheimer's disease research tools and are now being used as Alzheimer's disease therapies. Conformation‐specific mAbs that target oligomeric and fibrillar Aβ assemblies are of particular interest, as these assemblies are associated with Alzheimer's disease pathogenesis and progression. This article reports the generation of rabbit mAbs against two different triangular trimers derived from Aβ. These antibodies are the first mAbs generated against Aβ oligomer mimics in which the high‐resolution structures of the oligomers are known. We describe the isolation of the mAbs using single B‐cell sorting of peripheral blood mononuclear cells (PBMCs) from immunized rabbits, the selectivity of the mAbs for the triangular trimers, the immunoreactivity of the mAbs with aggregated Aβ 42 , and the immunoreactivity of the mAbs in brain tissue from the 5xFAD Alzheimer's disease mouse model. The characterization of these mAbs against structurally defined trimers derived from Aβ enhances understanding of antibody‐amyloid recognition and may benefit the development of diagnostics and immunotherapies in Alzheimer's disease.
{"title":"Generation and study of antibodies against two triangular trimers derived from Aβ","authors":"Adam G. Kreutzer, Ryan J. Malonis, Chelsea Marie T. Parrocha, Karen Tong, Gretchen Guaglianone, Jennifer T. Nguyen, Michelle N. Diab, Jonathan R. Lai, James S. Nowick","doi":"10.1002/pep2.24333","DOIUrl":"https://doi.org/10.1002/pep2.24333","url":null,"abstract":"Abstract Monoclonal antibodies (mAbs) that target the β‐amyloid peptide (Aβ) are important Alzheimer's disease research tools and are now being used as Alzheimer's disease therapies. Conformation‐specific mAbs that target oligomeric and fibrillar Aβ assemblies are of particular interest, as these assemblies are associated with Alzheimer's disease pathogenesis and progression. This article reports the generation of rabbit mAbs against two different triangular trimers derived from Aβ. These antibodies are the first mAbs generated against Aβ oligomer mimics in which the high‐resolution structures of the oligomers are known. We describe the isolation of the mAbs using single B‐cell sorting of peripheral blood mononuclear cells (PBMCs) from immunized rabbits, the selectivity of the mAbs for the triangular trimers, the immunoreactivity of the mAbs with aggregated Aβ 42 , and the immunoreactivity of the mAbs in brain tissue from the 5xFAD Alzheimer's disease mouse model. The characterization of these mAbs against structurally defined trimers derived from Aβ enhances understanding of antibody‐amyloid recognition and may benefit the development of diagnostics and immunotherapies in Alzheimer's disease.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135155463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Selene M. C. Cannelli, Ritvik Gupta, Tan Nguyen, Arunava Poddar, Srishti Sharma, Prachiti V. Vithole, Tony Z. Jia
Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares compositional aspects of modern biological condensates and primitive LLPS is necessary. Here, we first focus on membraneless organelles composed of intrinsically disordered proteins (IDPs) and nucleic acids. Then, as a parallel, we explore primitive membraneless compartments composed of simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare composition of modern biological condensates and primitive phase‐separated compartments, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane‐bound cells. This review aims to provide a compositional comparison of modern and primitive phase‐separated structures in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed.
{"title":"A compositional view comparing modern biological condensates and primitive phase‐separated compartment","authors":"Selene M. C. Cannelli, Ritvik Gupta, Tan Nguyen, Arunava Poddar, Srishti Sharma, Prachiti V. Vithole, Tony Z. Jia","doi":"10.1002/pep2.24331","DOIUrl":"https://doi.org/10.1002/pep2.24331","url":null,"abstract":"Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares compositional aspects of modern biological condensates and primitive LLPS is necessary. Here, we first focus on membraneless organelles composed of intrinsically disordered proteins (IDPs) and nucleic acids. Then, as a parallel, we explore primitive membraneless compartments composed of simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare composition of modern biological condensates and primitive phase‐separated compartments, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane‐bound cells. This review aims to provide a compositional comparison of modern and primitive phase‐separated structures in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44488885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PASylation has been recently reported as a feasible alternative to PEGylation, which in essence is using polypeptides constituted of a combination of proline, alanine and serine for the hydrophilic modification of pharmaceuticals. In this work, we focused on the biocompatibility evaluation of two PAS peptides, (PAS)8 and (PA3)7 as well as the more frequently used polymers polyethylene glycol (PEG) and polyglycerol (PG). It has been verified in this study that (PAS)8 and (PA3)7 both exhibited low cell toxicity against HUVEC and RAW 264.7 cell lines. They also showed negligible RBC hemolysis and agglutination, which demonstrated adequate hemocompatibility. Their potential interactions with bovine serum albumin have also been investigated, and the results indicated little hydrophobic interactions between the polymers and protein. In conclusion, (PAS)8 and (PA3)7 as well as PEG and PG all showed considerable compatibility and safety in these studies, suggesting that (PAS)8 and (PA3)7 could be considered as potential candidates for PEG replacement in future studies.
{"title":"An in vitro evaluation of the biocompatibility of proline‐alanine‐serine peptides compared with polyethylene glycol and polyglycerol","authors":"Qianyu Zhang, Hongjing Chen, Huali Chen","doi":"10.1002/pep2.24330","DOIUrl":"https://doi.org/10.1002/pep2.24330","url":null,"abstract":"PASylation has been recently reported as a feasible alternative to PEGylation, which in essence is using polypeptides constituted of a combination of proline, alanine and serine for the hydrophilic modification of pharmaceuticals. In this work, we focused on the biocompatibility evaluation of two PAS peptides, (PAS)8 and (PA3)7 as well as the more frequently used polymers polyethylene glycol (PEG) and polyglycerol (PG). It has been verified in this study that (PAS)8 and (PA3)7 both exhibited low cell toxicity against HUVEC and RAW 264.7 cell lines. They also showed negligible RBC hemolysis and agglutination, which demonstrated adequate hemocompatibility. Their potential interactions with bovine serum albumin have also been investigated, and the results indicated little hydrophobic interactions between the polymers and protein. In conclusion, (PAS)8 and (PA3)7 as well as PEG and PG all showed considerable compatibility and safety in these studies, suggesting that (PAS)8 and (PA3)7 could be considered as potential candidates for PEG replacement in future studies.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44715586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The scenario involving the alarming growth of bacterial resistance has never been more worrying. Increasingly selective and sophisticated bacterial strains resistant to traditional antibiotics are a threat to the health system worldwide. Therefore, antimicrobial peptides (AMPs) represent a promising path in the fight against multidrug‐resistant pathogens. Here, using an in silico methodology, employing robust software, the present study aims to analyze the chymo32 peptide, obtained by enzymatic fragmentation of the escapin protein to test its possible antibacterial effects, correlating them with their physical–chemical nature. In this study, we used in silico predictions such as structural prediction, physicochemical properties, hemolytic activity, and prediction of activity for immunomodulation. Among the 378 peptide fragments obtained from the original protein, chymo32 was the only peptide selected in the field of screenings involving sequence length, cationicity, hydrophobicity, and prediction of antibacterial activity. The physical–chemical properties of chymo32 are promising, as well as its prediction as AMP. The immunomodulation predictions showed no immunogenic potential, which indicates greater safety in the posterior steps in vitro, also highlighting the absence of hemolytic activity, one of the main problems associated with AMPs in the therapeutic clinic.
{"title":"Theoretical study of CHYMO32 peptide obtained by in silico fragmentation of the escapin protein isolated from marine hare Aplysia californica: A prediction for antimicrobial activity","authors":"Macley Silva Cardoso, J. M. Boeira","doi":"10.1002/pep2.24329","DOIUrl":"https://doi.org/10.1002/pep2.24329","url":null,"abstract":"The scenario involving the alarming growth of bacterial resistance has never been more worrying. Increasingly selective and sophisticated bacterial strains resistant to traditional antibiotics are a threat to the health system worldwide. Therefore, antimicrobial peptides (AMPs) represent a promising path in the fight against multidrug‐resistant pathogens. Here, using an in silico methodology, employing robust software, the present study aims to analyze the chymo32 peptide, obtained by enzymatic fragmentation of the escapin protein to test its possible antibacterial effects, correlating them with their physical–chemical nature. In this study, we used in silico predictions such as structural prediction, physicochemical properties, hemolytic activity, and prediction of activity for immunomodulation. Among the 378 peptide fragments obtained from the original protein, chymo32 was the only peptide selected in the field of screenings involving sequence length, cationicity, hydrophobicity, and prediction of antibacterial activity. The physical–chemical properties of chymo32 are promising, as well as its prediction as AMP. The immunomodulation predictions showed no immunogenic potential, which indicates greater safety in the posterior steps in vitro, also highlighting the absence of hemolytic activity, one of the main problems associated with AMPs in the therapeutic clinic.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49146729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toward a broad‐spectrum peptide‐based inhibitor of small multidrug resistance efflux pumps","authors":"Chloe J. Mitchell, Kha M. Nguyen, C. Deber","doi":"10.1002/pep2.24327","DOIUrl":"https://doi.org/10.1002/pep2.24327","url":null,"abstract":"","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"1 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42043872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bicyclic peptides: Paving the road for therapeutics of the future","authors":"S. Ullrich, Christoph Nitsche","doi":"10.1002/pep2.24326","DOIUrl":"https://doi.org/10.1002/pep2.24326","url":null,"abstract":"","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46934652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Swati Singh, Varshita Srivastava, P. Godara, H. Banavath, Harshita Tak, Arya Nayak, D. Kumari, B. Naik, D. Prusty
Monkeypox is a zoonotic disease caused by the Poxviridiea family virus Monkeypox. According to the Centers for Disease Control and Prevention, 70,420 monkeypox virus infections had been reported in 107 countries as of October 6, 2022. New studies have concluded that the monkeypox outbreak is caused by a strain with a unique mutation, increasing the possibility that the virus may develop resistance to current medicines by accumulating mutations in therapeutic targets. As peptide‐based therapeutics impede the drug target through multiple interactions, it may offer a better therapeutic solution to the possible drug resistance issue related to monkeypox treatment. Therefore, in this work, we screened an antiviral peptide library, the CPP site 2.0 database, against the p37 target protein using molecular docking approaches. The p37 is required for the viral pathogen's successful egression and spread. The allergenicity and physicochemical properties of the peptides were thoroughly analyzed before the molecular docking studies for selecting druggable candidates. The interactions of the peptides bearing the highest docking score were validated further by using molecular dynamics (MD) simulation studies. Our investigation revealed that two cell‐penetrating peptides of the CPP site 2.0 database might effectively prevent the egression and spread of the MPXV by inhibiting p37. Following more testing, these peptides can be explored in developing peptide‐based therapies against the MPX therapy.
{"title":"An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target","authors":"Swati Singh, Varshita Srivastava, P. Godara, H. Banavath, Harshita Tak, Arya Nayak, D. Kumari, B. Naik, D. Prusty","doi":"10.1002/pep2.24325","DOIUrl":"https://doi.org/10.1002/pep2.24325","url":null,"abstract":"Monkeypox is a zoonotic disease caused by the Poxviridiea family virus Monkeypox. According to the Centers for Disease Control and Prevention, 70,420 monkeypox virus infections had been reported in 107 countries as of October 6, 2022. New studies have concluded that the monkeypox outbreak is caused by a strain with a unique mutation, increasing the possibility that the virus may develop resistance to current medicines by accumulating mutations in therapeutic targets. As peptide‐based therapeutics impede the drug target through multiple interactions, it may offer a better therapeutic solution to the possible drug resistance issue related to monkeypox treatment. Therefore, in this work, we screened an antiviral peptide library, the CPP site 2.0 database, against the p37 target protein using molecular docking approaches. The p37 is required for the viral pathogen's successful egression and spread. The allergenicity and physicochemical properties of the peptides were thoroughly analyzed before the molecular docking studies for selecting druggable candidates. The interactions of the peptides bearing the highest docking score were validated further by using molecular dynamics (MD) simulation studies. Our investigation revealed that two cell‐penetrating peptides of the CPP site 2.0 database might effectively prevent the egression and spread of the MPXV by inhibiting p37. Following more testing, these peptides can be explored in developing peptide‐based therapies against the MPX therapy.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43220124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：