Search results for: viral evolution
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2146

Search results for: viral evolution

2146 Cellular RNA-Binding Domains with Distant Homology in Viral Proteomes

Authors: German Hernandez-Alonso, Antonio Lazcano, Arturo Becerra

Abstract:

Until today, viruses remain controversial and poorly understood; about their origin, this problem represents an enigma and one of the great challenges for the contemporary biology. Three main theories have tried to explain the origin of viruses: regressive evolution, escaped host gene, and pre-cellular origin. Under the perspective of the escaped host gene theory, it can be assumed a cellular origin of viral components, like protein RNA-binding domains. These universal distributed RNA-binding domains are related to the RNA metabolism processes, including transcription, processing, and modification of transcripts, translation, RNA degradation and its regulation. In the case of viruses, these domains are present in important viral proteins like helicases, nucleases, polymerases, capsid proteins or regulation factors. Therefore, they are implicated in the replicative cycle and parasitic processes of viruses. That is why it is possible to think that those domains present low levels of divergence due to selective pressures. For these reasons, the main goal for this project is to create a catalogue of the RNA-binding domains found in all the available viral proteomes, using bioinformatics tools in order to analyze its evolutionary process, and thus shed light on the general virus evolution. ProDom database was used to obtain larger than six thousand RNA-binding domain families that belong to the three cellular domains of life and some viral groups. From the sequences of these families, protein profiles were created using HMMER 3.1 tools in order to find distant homologous within greater than four thousand viral proteomes available in GenBank. Once accomplished the analysis, almost three thousand hits were obtained in the viral proteomes. The homologous sequences were found in proteomes of the principal Baltimore viral groups, showing interesting distribution patterns that can contribute to understand the evolution of viruses and their host-virus interactions. Presence of cellular RNA-binding domains within virus proteomes seem to be explained by closed interactions between viruses and their hosts. Recruitment of these domains is advantageous for the viral fitness, allowing viruses to be adapted to the host cellular environment.

Keywords: bioinformatics tools, distant homology, RNA-binding domains, viral evolution

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2145 Viral Advertising: Popularity and Willingness to Share among the Czech Internet Population

Authors: Martin Klepek

Abstract:

This paper presents results of primary quantitative research on viral advertising with focus on popularity and willingness to share viral video among Czech Internet population. It starts with brief theoretical debate on viral advertising, which is used for the comparison of the results. For purpose of collecting data, online questionnaire survey was given to 384 respondents. Statistics utilized in this research included frequency, percentage, correlation and Pearson’s Chi-square test. Data was evaluated using SPSS software. The research analysis disclosed high popularity of viral advertising video among Czech Internet population but implies lower willingness to share it. Significant relationship between likability of viral video technique and age of the viewer was found.

Keywords: internet advertising, internet population, promotion, marketing communication, viral advertising, viral video

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2144 Evolutionary Prediction of the Viral RNA-Dependent RNA Polymerase of Chandipura vesiculovirus and Related Viral Species

Authors: Maneesh Kumar, Roshan Kamal Topno, Manas Ranjan Dikhit, Vahab Ali, Ganesh Chandra Sahoo, Bhawana, Major Madhukar, Rishikesh Kumar, Krishna Pandey, Pradeep Das

Abstract:

Chandipura vesiculovirus is an emerging (-) ssRNA viral entity belonging to the genus Vesiculovirus of the family Rhabdoviridae, associated with fatal encephalitis in tropical regions. The multi-functionally active viral RNA-dependent RNA polymerase (vRdRp) that has been incorporated with conserved amino acid residues in the pathogens, assigned to synthesize distinct viral polypeptides. The lack of proofreading ability of the vRdRp produces many mutated variants. Here, we have performed the evolutionary analysis of 20 viral protein sequences of vRdRp of different strains of Chandipura vesiculovirus along with other viral species from genus Vesiculovirus inferred in MEGA6.06, employing the Neighbour-Joining method. The p-distance algorithmic method has been used to calculate the optimum tree which showed the sum of branch length of about 1.436. The percentage of replicate trees in which the associated taxa are clustered together in the bootstrap test (1000 replicates), is shown next to the branches. No mutation was observed in the Indian strains of Chandipura vesiculovirus. In vRdRp, 1230(His) and 1231(Arg) are actively participated in catalysis and, are found conserved in different strains of Chandipura vesiculovirus. Both amino acid residues were also conserved in the other viral species from genus Vesiculovirus. Many isolates exhibited maximum number of mutations in catalytic regions in strains of Chandipura vesiculovirus at position 26(Ser→Ala), 47 (Ser→Ala), 90(Ser→Tyr), 172(Gly→Ile, Val), 172(Ser→Tyr), 387(Asn→Ser), 1301(Thr→Ala), 1330(Ala→Glu), 2015(Phe→Ser) and 2065(Thr→Val) which make them variants under different tropical conditions from where they evolved. The result clarifies the actual concept of RNA evolution using vRdRp to develop as an evolutionary marker. Although, a limited number of vRdRp protein sequence similarities for Chandipura vesiculovirus and other species. This might endow with possibilities to identify the virulence level during viral multiplication in a host.

Keywords: Chandipura, (-) ssRNA, viral RNA-dependent RNA polymerase, neighbour-joining method, p-distance algorithmic, evolutionary marker

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2143 Ocular Manifestations of Recent Viral Pandemics: A Literature Review

Authors: Mohammad J. J. Taha, Mohammad T. Abuawwad, Warda A. Alrubasy, Shams Khalid Sameer, Taleb Alsafi, Yaqeen Al-Bustanji, Luai Abu-Ismail, Abdulqadir J. Nashwan

Abstract:

Viral pandemics often take the world by storm, urging the medical community to prioritize the most evident systemic manifestations, often causing ocular manifestations to go unnoticed. This literature review aims to highlight the ocular complications of monkeypox, SARS-CoV-2, MERS, ebola, H1N1, and zika viruses as the most recent viral pandemics. Since the emergence of the newly resurfacing monkeypox and the novel SARS-CoV-2, research aiming to uncover the effects of these pandemics began right away. Moreover, it also discusses the ocular complications of the vaccines and treatments that were used in the scope of the viral pandemics. To add, this work discussed the role of the eye as an important route of viral transmission, and thereafter, the American Academy of Ophthalmology (AAO) recommendations to reduce the incidence of viral transmission were mentioned. Finally, this paper aims to outline a platform for researchers who are interested in further investigating eye-related viral manifestations.

Keywords: ophthalmology, monkeypox, ebola, zika, MERS, H1N1, influenza, COVID-19

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2142 Metagenomics-Based Molecular Epidemiology of Viral Diseases

Authors: Vyacheslav Furtak, Merja Roivainen, Olga Mirochnichenko, Majid Laassri, Bella Bidzhieva, Tatiana Zagorodnyaya, Vladimir Chizhikov, Konstantin Chumakov

Abstract:

Molecular epidemiology and environmental surveillance are parts of a rational strategy to control infectious diseases. They have been widely used in the worldwide campaign to eradicate poliomyelitis, which otherwise would be complicated by the inability to rapidly respond to outbreaks and determine sources of the infection. The conventional scheme involves isolation of viruses from patients and the environment, followed by their identification by nucleotide sequences analysis to determine phylogenetic relationships. This is a tedious and time-consuming process that yields definitive results when it may be too late to implement countermeasures. Because of the difficulty of high-throughput full-genome sequencing, most such studies are conducted by sequencing only capsid genes or their parts. Therefore the important information about the contribution of other parts of the genome and inter- and intra-species recombination to viral evolution is not captured. Here we propose a new approach based on the rapid concentration of sewage samples with tangential flow filtration followed by deep sequencing and reconstruction of nucleotide sequences of viruses present in the samples. The entire nucleic acids content of each sample is sequenced, thus preserving in digital format the complete spectrum of viruses. A set of rapid algorithms was developed to separate deep sequence reads into discrete populations corresponding to each virus and assemble them into full-length consensus contigs, as well as to generate a complete profile of sequence heterogeneities in each of them. This provides an effective approach to study molecular epidemiology and evolution of natural viral populations.

Keywords: poliovirus, eradication, environmental surveillance, laboratory diagnosis

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2141 Cyclic Evolution of a Two Fluid Diffusive Universe

Authors: Subhayan Maity

Abstract:

Complete scenario of cosmic evolution from emergent phase to late time acceleration (i.e. non-singular ever expanding Universe) is a popular preference in the recent cosmology. Yet one can’t exclude the idea that other type of evolution pattern of the Universe may also be possible. Especially, the bouncing scenario is becoming a matter of interest now a days. The present work is an exhibition of such a different pattern of cosmic evolution where the evolution of Universe has been shown as a cyclic thermodynamic process. Under diffusion mechanism (non-equilibrium thermodynamic process), the cosmic evolution has been modelled as [ emergent - accelerated expansion - decelerated expansion - decelerated contraction - accelerated contraction - emergent] .

Keywords: non-equilibrium thermodynamics, non singular evolution of universe, cyclic evolution, diffusive fluid

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2140 Antiviral Activity of Interleukin-11 in Response to Porcine Epidemic Diarrhea Virus Infection

Authors: Li Yuchen, Wu Qingxin, Jin Yuxing, Yang Qian

Abstract:

Interleukin-11 (IL-11), a well-known anti-inflammatory factor, helps to protect against intestinal epithelium damage caused by physical or chemical factors. However, little is known about the role of IL-11 during viral infection. Herein, high mRNA and protein levels of IL-11 were found in epithelial cells and jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, and IL-11 expression was positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) suppressed PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 inhibited viral infection by preventing PEDV-mediated apoptosis of cells through activating the IL-11/STAT3 signal pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggested that that IL-11 is a novel PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential uses of IL-11 as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.

Keywords: Interleukin-11, Porcine epidemic diarrhea virus, STAT3, anti-apoptosis

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2139 Ethnobotanical Study of Spontaneous Medicinal Plants Used in the Treatment of Viral Respiratory Diseases in the Prerif, Morocco

Authors: El Amane Salma, Rahou Abdelilah

Abstract:

Viral respiratory infections (common cold, flu, sinusitis, bronchiolitis, etc.) are among the most common infections in the world with severe symptoms. In Morocco, as everywhere in the world, especially in developing countries, the therapeutic indications of medicinal plants are very present to treat several diseases, including the respiratory system. The objective of our study is to identify and document medicinal plants used in traditional medicine to treat viral respiratory infections and alleviate their symptoms in order to generate interest for future studies in verifying the efficacy of these traditional medicines and their conservation. The information acquired from 81 questionnaires and the floristic identification allowed us to identify 19 spontaneous species belonging to 11 families, used as traditional therapies for viral respiratory diseases in the Prerif. The herbs are the most used life form. The results also showed that leaves were the most commonly used plant parts and most of the herbal medicines were prepared in the form of infusions and administered orally. Documented data was evaluated using use value (UV), family importance value (FIV) and relative frequency citation (RCF).

Keywords: medicinal plants, ethnobotanical, ethnopharmacological, viral respiratory diseases, Morocco

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2138 Developing a Viral Artifact to Improve Employees’ Security Behavior

Authors: Stefan Bauer, Josef Frysak

Abstract:

According to the scientific information management literature, the improper use of information technology (e.g. personal computers) by employees are one main cause for operational and information security loss events. Therefore, organizations implement information security awareness programs to increase employees’ awareness to further prevention of loss events. However, in many cases these information security awareness programs consist of conventional delivery methods like posters, leaflets, or internal messages to make employees aware of information security policies. We assume that a viral information security awareness video might be more effective medium than conventional methods commonly used by organizations. The purpose of this research is to develop a viral video artifact to improve employee security behavior concerning information technology.

Keywords: information security awareness, delivery methods, viral videos, employee security behavior

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2137 Immunity Boosting and Balanced Diet Prevents Viral Infections with Special Emphasis on COVID-19

Authors: K. R. Padma, K. R. Don

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Background and aims: A balanced nutritional diet is essential in maintaining immunity and for deterrence as well as desisting of viral infections. Nevertheless, currently, very less information is available online regarding nutrition consumption during the period of coronavirus infection, i.e. (COVID-19). In our systematic review article, we portrayed and aimed to evaluate evidence from various previous clinical trials, which was based on nutritional interventions for viral diseases and given a concise overview. Methods: A systematic search was carried out employing 3 key medical databases: PubMed®, Web of Science®, and SciVerse Scopus®. Studies were performed and evaluated suitable if clinical trials in humans, appropriate immunological parameters on viral and respiratory infections, need to perform. Basic Clinical trials on nutritional vitamins, minerals, nutraceuticals as well as probiotics were included. Results: We have explored 10 review articles and extracted data for our study. A total of > 2000 participants were included and excluded several other trace elements as well as various vitamins, but in inclusion criteria mainly concentrated on those who have shown propitious immune-modulatory effects against viral respiratory infections. Conclusions: We have encapsulated the potential health benefits of some minerals, vitamins, as well as certain designer foods, nutraceuticals, and probiotics in viral infections. Based on this nutritional interventional strategy available from our present data, it could be promising to abstain and reduce the COVID-19 infection replication and boost our immunity to fight against the virus.

Keywords: COVID-19, immunity, vitamins, nutritional intervention strategy

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2136 Viral Metagenomics Revealed a Cardiovirus in Feces of Wild Rats

Authors: Shama, Asif Mahmood, Wen Zhang

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Cardiovirus is a genus of viruses belonging to the family Picornaviridae. Here, we used viral metagenomic techniques to detect the viral nucleic acid in the fecal samples from wild rats in Zhenjiang city in China. Fecal samples were collected from 20 wild rats and pooled into four sample pools and then subjected to library construction, which were then sequenced on the Illumina MiSeq platform. The sequenced reads were analyzed using a viral metagenomic analysis pipeline. A cardiovirus from the feces of a wild rat was identified, named amzj-2018, of which the complete genome was acquired. Phylogenetic analysis based on the complete amino acid sequence of polyprotein revealed that amzj-2018 formed a separate branch located between clusters of Saffold virus and Rat Theilovirus 1 (RTV-1). Phylogenetic analysis based on different regions of the polyproteins, including P1, P2, P3, and P2+P3, respectively, showed discordant trees, where the tree based on the P3 region indicated that amzj-2018 clustered separately between Theiler's murine encephalomyelitis virus and RTV-1. The complete genome of a cardiovirus was determined from the feces of wild rats, which belonged to a novel type of cardiovirus based on phylogenetic analysis. Whether it is associated with disease needs further investigation.

Keywords: cardioviruses, viral metagenomics, novel viruses, virus-host interaction

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2135 Aptamers: A Potential Strategy for COVID-19 Treatment

Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

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Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

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2134 A Novel Peptide Showing Universal Effect against Multiple Viruses in Vitro and in Vivo

Authors: Hanjun Zhao, Ke Zhang, Bojian Zheng

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Background: So far, there is no universal antiviral agent which can inhibit multiple viral infections. More and more drug-resistant viral strains emerge after the antiviral drug application for treatment. Defensins are the front line of host innate immunity and have broad spectrum antibacterial and antiviral effects. However, there is limited data to show if these defensins have good antiviral activity in vivo and what the antiviral mechanism is. Subjects: To investigate a peptide with widespread antivirus activity in vitro and in vivo and illustrate the antiviral mechanism. Methods: Antiviral peptide library designed from mouse beta defensins was synthesized by the company. Recombinant beta defensin was obtained from E. coli. Antiviral activity in vitro was assayed by plaque assay, qPCR. Antiviral activity in vivo was detected by animal challenge with 2009 pandemic H1N1 influenza A virus. The antiviral mechanism was assayed by western blot, ELISA, and qPCR. Conclusions: We identify a new peptide which has widespread effects against multiple viruses (H1N1, H5N1, H7N9, MERS-CoV) in vitro and has efficient antivirus activity in vivo. This peptide inhibits viral entry into target cells and subsequently blocks viral replication. The in vivo study of the antiviral peptide against other viral infections and the investigation of its more detail antiviral mechanism are ongoing.

Keywords: antiviral peptide, defensin, Influenza A virus, mechanism

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2133 The Risk of Deaths from Viral Hepatitis among the Female Workers in the Beauty Service Industry

Authors: Byeongju Choi, Sanggil Lee, Kyung-Eun Lee

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Introduction: In the republic of Korea, the number of workers in the beauty industry has been increasing. Because the prevalence of hepatitis B carriers in Korea is higher than in other countries, the risk of blood-borne infection including viral hepatitis B and C, among the workers by using the sharp and contaminated instruments during procedure can be expected among beauty salon workers. However, the health care policies for the workers to prevent the blood-borne infection are not established due to the lack of evidences. Moreover, the workers in hair and nail salon were mostly employed at small businesses, where national mandatory systems or policies for workers’ health management are not applied. In this study, the risk of the viral hepatitis B and C from the job experiencing the hair and nail procedures in the mortality was assessed. Method: We conducted a retrospective review of the job histories and causes of death in the female deaths from 2006-2016. 132,744 of female deaths who had one more job experiences during their lifetime were included in this study. Job histories were assessed using the employment insurance database in Korea Employment Information Service (KEIS) and the causes of death were in death statistics produced by Statistics Korea. Case group (n= 666) who died from viral hepatitis was classified the death having record involved in ‘B15-B19’ as a cause of deaths based on Korean Standard Classification of Diseases(KCD) with the deaths from other causes, control group (n=132,078). The group of the workers in the beauty service industry were defined as the employees who had ever worked in the industry coded as ‘9611’ based on Korea Standard Industry Classification (KSIC) and others were others. Other than job histories, birth year, marital status, education level were investigated from the death statistics. Multiple logistic regression analysis were used to assess the risk of deaths from viral hepatitis in the case and control group. Result: The number of the deaths having ever job experiences at the hair and nail salon was 255. After adjusting confounders of age, marital status and education, the odds ratio(OR) for deaths from viral hepatitis was quite high in the group having experiences with working in the beauty service industry with 3.14(95% confidence interval(CI) 1.00-9.87). Other associated factors with increasing the risk of deaths from viral hepatitis were low education level(OR=1.34, 95% CI 1.04-1.73), married women (OR=1.42, 95% CI 1.02-1.97). Conclusion: The risk of deaths from viral hepatitis were high in the workers in the beauty service industry but not statistically significant, which might attributed from the small number of workers in beauty service industry. It was likely that the number of workers in beauty service industry could be underestimated due to their temporary job position. Further studies evaluating the status and the incidence of viral infection among the workers with consideration of the vertical transmission would be required.

Keywords: beauty service, viral hepatitis, blood-borne infection, viral infection

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2132 Investigation of Possible Precancerous Viral Markers in Dental Follicles of Asymptomatic Impacted Teeth

Authors: Serap Keskin Tunç, Cennet Neslihan Eroğlu, Sevinç Şahin, Selda Seçkin

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It has been suggested that various viruses may play a role in the pathogenesis of cancerous oral lesions in the literature. The aim of this study was to investigate the presence of both possible precancerous viral markers (HPV, HHV8, HSV1, HSV2, and EBV), and p53 and Ki-67 in the dental follicles of asymptomatic impacted teeth. A hundred healthy volunteers, older than 18 years old, included in the study. Dental follicles of extracted impacted teeth were excised and fixated in 10% formaldehyde. Histopathological and immunohistochemical examinations using HPV (containing HPV 8 and HPV 11), p16 (containing HPV 16), HHV8, HSV1, HSV2, EBV, p53 and Ki-67 antibodies were carried out. Also, the immunohistochemical results were correlated with the clinicopathological feature by Chi-square test statistically No dysplasia or neoplasm was observed. 62% of the cases were positive for p16, 32% were positive for EBV, 26% were positive for HSV1, immunohistochemically. All cases were immunonegative for HPV, HSV2, and HHV8. There was statistically significant correlation between overexpression of p53 with both EBV and p16 positivity (p<0.05). Direct correlation between higher expression of Ki-67 between EBV immunopositivity was detected (p<0.05). Thus, these viruses may be suggested to show trophism to the dental follicles acting as a reservoir. In conclusion, all dental follicles of extracted impacted teeth should be examined histopathologically in order to detect and prevent possible viral oncogenesis.

Keywords: dental follicles, Ki67, p53, precancerous markers viral markers

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2131 A Novel Epitope Prediction for Vaccine Designing against Ebola Viral Envelope Proteins

Authors: Manju Kanu, Subrata Sinha, Surabhi Johari

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Viral proteins of Ebola viruses belong to one of the best studied viruses; however no effective prevention against EBOV has been developed. Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with Ebola virus as a model system. Hence great challenge in the field of ebola virus research is to design universal vaccine. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertypes Human Leukocyte Antigen (HLA) alleles. MUSCLE and MOTIF tools were used to find out most conserved peptide sequences of viral proteins. Immunoinformatics tools were used for prediction of immunogenic peptides of viral proteins in zaire strains of Ebola virus. Putative epitopes for viral proteins (VP) were predicted from conserved peptide sequences of VP. Three tools NetCTL 1.2, BIMAS and Syfpeithi were used to predict the Class I putative epitopes while three tools, ProPred, IEDB-SMM-align and NetMHCII 2.2 were used to predict the Class II putative epitopes. B cell epitopes were predicted by BCPREDS 1.0. Immunogenic peptides were identified and selected manually by putative epitopes predicted from online tools individually for both MHC classes. Finally sequences of predicted peptides for both MHC classes were looked for common region which was selected as common immunogenic peptide. The immunogenic peptides were found for viral proteins of Ebola virus: epitopes FLESGAVKY, SSLAKHGEY. These predicted peptides could be promising candidates to be used as target for vaccine design.

Keywords: epitope, b cell, immunogenicity, ebola

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2130 Multilevel of Factors Affected Optimal Adherence to Antiretroviral Therapy and Viral Suppression amongst HIV-Infected Prisoners in South Ethiopia: A Prospective Cohort Study

Authors: Terefe Fuge, George Tsourtos , Emma Miller

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Objectives: Maintaining optimal adherence and viral suppression in people living with HIV (PLWHA) is essential to ensure both preventative and therapeutic benefits of antiretroviral therapy (ART). Prisoners bear a particularly high burden of HIV infection and are highly likely to transmit to others during and after incarceration. However, the level of adherence and viral suppression, as well as its associated factors in incarcerated populations in low-income countries is unknown. This study aimed to determine the prevalence of non-adherence and viral failure, and contributing factors to this amongst prisoners in South Ethiopia. Methods: A prospective cohort study was conducted between June 1, 2019 and July 31, 2020 to compare the level of adherence and viral suppression between incarcerated and non-incarcerated PLWHA. The study involved 74 inmates living with HIV (ILWHA) and 296 non-incarcerated PLWHA. Background information including sociodemographic, socioeconomic, psychosocial, behavioural, and incarceration-related characteristics was collected using a structured questionnaire. Adherence was determined based on participants’ self-report and pharmacy refill records, and plasma viral load measurements which were undertaken within the study period were prospectively extracted to determine viral suppression. Various univariate and multivariate regression models were used to analyse data. Results: Self-reported dose adherence was approximately similar between ILWHA and non-incarcerated PLWHA (81% and 83% respectively), but ILWHA had a significantly higher medication possession ratio (MPR) (89% vs 75%). The prevalence of viral failure (VF) was slightly higher (6%) in ILWHA compared to non-incarcerated PLWHA (4.4%). The overall dose non-adherence (NA) was significantly associated with missing ART appointments, level of satisfaction with ART services, patient’s ability to comply with a specified medication schedule and types of methods used to monitor the schedule. In ILWHA specifically, accessing ART services from a hospital compared to a health centre, an inability to always attend clinic appointments, experience of depression and a lack of social support predicted NA. VF was significantly higher in males, people of age 31-35 years and in those who experienced social stigma, regardless of their incarceration status. Conclusions: This study revealed that HIV-infected prisoners in South Ethiopia were more likely to be non-adherent to doses and so to develop viral failure compared to their non-incarcerated counterparts. A multitude of factors was found to be responsible for this requiring multilevel intervention strategies focusing on the specific needs of prisoners.

Keywords: Adherence , Antiretroviral therapy, Incarceration, South Ethiopia, Viral suppression

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2129 Factors Associated with Cytomegalovirus Infection: A Prospective Single Centre Study

Authors: Marko Jankovic, Aleksandra Knezevic, Maja Cupic, Dragana Vujic, Zeljko Zecevic, Borko Gobeljic, Marija Simic, Tanja Jovanovic

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The human cytomegalovirus (CMV) is a notorious pathogen in the pediatric transplant setting. Although studies on factors in complicity with CMV infection abound, the role of age, gender, allogeneic hematopoietic stem cell transplantation (alloHSCT) modality, and underlying disease as regards CMV infection and viral load in children are poorly explored. We examined the significance of various factors related to the risk of CMV infection and viral load in Serbian children and adolescents undergoing alloHSCT. This was a prospective single centre study of thirty two pediatric patients in receipt of alloHSCT for various malignant and non-malignant disorders. Screening for active viral infection was performed by regular weekly monitoring. The Real-Time PCR method was used for CMV DNA detection and quantitation. Statistical analysis was performed using the IBM SPSS Statistics v20 software. Chi-square test was used to evaluate categorical variables. Comparison between scalar and nominal data was done by Wilcoxon-Mann-Whitney test. Pearson correlation was applied for studying the association between patient age and viral load. CMV was detected in 23 (71.9%) patients. Infection occurred significantly more often (p=0.015) in patients with haploidentical donors. The opposite was noted for matched sibling grafts (p=0.006). The viral load was higher in females (p=0.041) and children in the aftermath of alloHSCT with malignant diseases (p=0.019). There was no significant relationship between the viral infection dynamics and overt medical consequences. This is the first study of risk factors for CMV infection in Serbian pediatric alloHSCT patients. Transplanted patients presented with a high incidence of CMV viremia. The HLA compatibility of donated graft is associated with the frequency of CMV positive events. Age, gender, underlying disease, and medically relevant events were not conducive to occurrences of viremia. Notably, substantial viral burdens were evidenced in females and patients with neoplastic diseases. Studies comprising larger populations are clearly needed to scrutinize current results.

Keywords: allogeneic hematopoietic stem cell transplantation, children, cytomegalovirus, risk factors, viral load

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2128 Hepatocyte-Intrinsic NF-κB Signaling Is Essential to Control a Systemic Viral Infection

Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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2127 Complex Fuzzy Evolution Equation with Nonlocal Conditions

Authors: Abdelati El Allaoui, Said Melliani, Lalla Saadia Chadli

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The objective of this paper is to study the existence and uniqueness of Mild solutions for a complex fuzzy evolution equation with nonlocal conditions that accommodates the notion of fuzzy sets defined by complex-valued membership functions. We first propose definition of complex fuzzy strongly continuous semigroups. We then give existence and uniqueness result relevant to the complex fuzzy evolution equation.

Keywords: Complex fuzzy evolution equations, nonlocal conditions, mild solution, complex fuzzy semigroups

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2126 Molecular Characterization and Phylogenetic Analysis of Influenza a(H3N2) Virus Circulating during the 2010-2011 in Riyadh, Saudi Arabia

Authors: Ghazanfar Ali, Fahad N Almajhdi

Abstract:

This study provides data on the viral diagnosis and molecular epidemiology of influenza A(H3N2) virus isolated in Riyadh, Saudi Arabia. Nasopharyngeal aspirates from 80 clinically infected patients in the peak of the 2010-2011 winter seasons were processed for viral diagnosis by RT-PCR. Sequencing of entire HA and NA genes of representative isolates and molecular epidemiological analysis were performed. A total of 06 patients were positive for influenza A, B and respiratory syncytial viruses by RT-PCR assays; out of these only one sample was positive for influenza A(H3N2) by RT-PCR. Phylogenetic analysis of the HA and NA gene sequences showed identities higher than 99-98.8 % in both genes. They were also similar to reference isolates in HA sequences (99 % identity) and in NA sequences (99 % identity). Amino acid sequences predicted for the HA gene were highly identical to reference strains. The NA amino acid substitutions identified did not include the oseltamivir-resistant H275Y substitution. Conclusion: Viral isolation and RT-PCR together were useful for diagnosis of the influenza A (H3N2) virus. Variations in HA and NA sequences are similar to those identified in worldwide reference isolates and no drug resistance was found.

Keywords: influenza A (H3N2), genetic characterization, viral isolation, RT-PCR, Saudi Arabia

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2125 Immune Modulation and Cytomegalovirus Reactivation in Sepsis-Induced Immunosuppression

Authors: G. Lambe, D. Mansukhani, A. Shetty, S. Khodaiji, C. Rodrigues, F. Kapadia

Abstract:

Introduction: Sepsis is known to cause impairment of both innate and adaptive immunity and involves an early uncontrolled inflammatory response, followed by a protracting immunosuppression phase, which includes decreased expression of cell receptors, T cell anergy and exhaustion, impaired cytokine production, which may cause high risk for secondary infections due to reduced response to antigens. Although human cytomegalovirus (CMV) is widely recognized as a serious viral pathogen in sepsis and immunocompromised patients, the incidence of CMV reactivation in patients with sepsis lacking strong evidence of immunosuppression is not well defined. Therefore, it is important to determine an association between CMV reactivation and sepsis-induced immunosuppression. Aim: To determine the association between incidence of CMV reactivation and immune modulation in sepsis-induced immunosuppression with time. Material and Methods: Ten CMV-seropositive adult patients with severe sepsis were included in this study. Blood samples were collected on Day 0, and further weekly up to 21 days. CMV load was quantified by real-time PCR using plasma. The expression of immunosuppression markers, namely, HLA-DR, PD-1, and regulatory T cells, were determined by flow cytometry using whole blood. Results: At Day 0, no CMV reactivation was observed in 6/10 patients. In these patients, the median length for reactivation was 14 days (range, 7-14 days). The remaining four patients, at Day 0, had a mean viral load of 1802+2599 copies/ml, which increased with time. At Day 21, the mean viral load for all 10 patients was 60949+179700 copies/ml, indicating that viremia increased with the length of stay in the hospital. HLA-DR expression on monocytes significantly increased from Day 0 to Day 7 (p = 0.001), following which no significant change was observed until Day 21, for all patients except 3. In these three patients, HLA-DR expression on monocytes showed a decrease at elevated viral load (>5000 copies/ml), indicating immune suppression. However, the other markers, PD-1 and regulatory T cells, did not show any significant changes. Conclusion: These preliminary findings suggest that CMV reactivation can occur in patients with severe sepsis. In fact, the viral load continued to increase with the length of stay in the hospital. Immune suppression, indicated by decreased expression of HLA-DR alone, was observed in three patients with elevated viral load.

Keywords: CMV reactivation, immune suppression, sepsis immune modulation, CMV viral load

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2124 An In-silico Pharmacophore-Based Anti-Viral Drug Development for Hepatitis C Virus

Authors: Romasa Qasim, G. M. Sayedur Rahman, Nahid Hasan, M. Shazzad Hosain

Abstract:

Millions of people worldwide suffer from Hepatitis C, one of the fatal diseases. Interferon (IFN) and ribavirin are the available treatments for patients with Hepatitis C, but these treatments have their own side-effects. Our research focused on the development of an orally taken small molecule drug targeting the proteins in Hepatitis C Virus (HCV), which has lesser side effects. Our current study aims to the Pharmacophore based drug development of a specific small molecule anti-viral drug for Hepatitis C Virus (HCV). Drug designing using lab experimentation is not only costly but also it takes a lot of time to conduct such experimentation. Instead in this in silico study, we have used computer-aided techniques to propose a Pharmacophore-based anti-viral drug specific for the protein domains of the polyprotein present in the Hepatitis C Virus. This study has used homology modeling and ab initio modeling for protein 3D structure generation followed by pocket identification in the proteins. Drug-able ligands for the pockets were designed using de novo drug design method. For ligand design, pocket geometry is taken into account. Out of several generated ligands, a new Pharmacophore is proposed, specific for each of the protein domains of HCV.

Keywords: pharmacophore-based drug design, anti-viral drug, in-silico drug design, Hepatitis C virus (HCV)

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2123 Distinguishing between Bacterial and Viral Infections Based on Peripheral Human Blood Tests Using Infrared Microscopy and Multivariate Analysis

Authors: H. Agbaria, A. Salman, M. Huleihel, G. Beck, D. H. Rich, S. Mordechai, J. Kapelushnik

Abstract:

Viral and bacterial infections are responsible for variety of diseases. These infections have similar symptoms like fever, sneezing, inflammation, vomiting, diarrhea and fatigue. Thus, physicians may encounter difficulties in distinguishing between viral and bacterial infections based on these symptoms. Bacterial infections differ from viral infections in many other important respects regarding the response to various medications and the structure of the organisms. In many cases, it is difficult to know the origin of the infection. The physician orders a blood, urine test, or 'culture test' of tissue to diagnose the infection type when it is necessary. Using these methods, the time that elapses between the receipt of patient material and the presentation of the test results to the clinician is typically too long ( > 24 hours). This time is crucial in many cases for saving the life of the patient and for planning the right medical treatment. Thus, rapid identification of bacterial and viral infections in the lab is of great importance for effective treatment especially in cases of emergency. Blood was collected from 50 patients with confirmed viral infection and 50 with confirmed bacterial infection. White blood cells (WBCs) and plasma were isolated and deposited on a zinc selenide slide, dried and measured under a Fourier transform infrared (FTIR) microscope to obtain their infrared absorption spectra. The acquired spectra of WBCs and plasma were analyzed in order to differentiate between the two types of infections. In this study, the potential of FTIR microscopy in tandem with multivariate analysis was evaluated for the identification of the agent that causes the human infection. The method was used to identify the infectious agent type as either bacterial or viral, based on an analysis of the blood components [i.e., white blood cells (WBC) and plasma] using their infrared vibrational spectra. The time required for the analysis and evaluation after obtaining the blood sample was less than one hour. In the analysis, minute spectral differences in several bands of the FTIR spectra of WBCs were observed between groups of samples with viral and bacterial infections. By employing the techniques of feature extraction with linear discriminant analysis (LDA), a sensitivity of ~92 % and a specificity of ~86 % for an infection type diagnosis was achieved. The present preliminary study suggests that FTIR spectroscopy of WBCs is a potentially feasible and efficient tool for the diagnosis of the infection type.

Keywords: viral infection, bacterial infection, linear discriminant analysis, plasma, white blood cells, infrared spectroscopy

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2122 A Small-Molecular Inhibitor of Influenza Virus via Disrupting the PA and PB1 Interaction of the Viral Polymerase

Authors: Shuofeng Yuan, Bojian Zheng

Abstract:

Assembly of the heterotrimeric polymerase complex of influenza virus from the individual subunits PB1, PA, and PB2 is a prerequisite for viral replication, in which the interaction between the N-terminal of PB1 (PB1N) and the C terminal of PA (PAC) may be a desired target for antiviral development. In this study, we first compared the feasibility of high throughput screening by enzyme-linked immunosorbent assay (ELISA) and fluorescence polarization (FP) assay. Among the two, ELISA was demonstrated to own broader dynamic range so that it was used for screening inhibitors, which blocked PA and PB1 interaction. Several binding inhibitors of PAC-PB1N were identified and subsequently tested for the antiviral efficacy. Apparently, 3-(2-chlorophenyl)-6-ethyl-7-methyl[1,2,4]triazolo[4,3-a]pyrimidin-5-ol, designated ANA-1, was found to be a strong inhibitor of PAC-PB1N interaction and act as a potent antiviral agent against the infections of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 subtypes, in cell cultures. Intranasal administration of ANA-1 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted that ANA-1 bound to an allosteric site of PAC, which would cause conformational changes thereby disrupting the PAC-PB1N interaction. Overall, our study has identified a novel compound with potential to be developed as an anti-influenza drug.

Keywords: influenza, antiviral, viral polymerase, compounds

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2121 Zika Virus NS5 Protein Potential Inhibitors: An Enhanced in silico Approach in Drug Discovery

Authors: Pritika Ramharack, Mahmoud E. S. Soliman

Abstract:

The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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2120 Multi-Scale Urban Spatial Evolution Analysis Based on Space Syntax: A Case Study in Modern Yangzhou, China

Authors: Dai Zhimei, Hua Chen

Abstract:

The exploration of urban spatial evolution is an important part of urban development research. Therefore, the evolutionary modern Yangzhou urban spatial texture was taken as the research object, and Spatial Syntax was used as the main research tool, this paper explored Yangzhou spatial evolution law and its driving factors from the urban street network scale, district scale and street scale. The study has concluded that at the urban scale, Yangzhou urban spatial evolution is the result of a variety of causes, including physical and geographical condition, policy and planning factors, and traffic conditions, and the evolution of space also has an impact on social, economic, environmental and cultural factors. At the district and street scales, changes in space will have a profound influence on the history of the city and the activities of people. At the end of the article, the matters needing attention during the evolution of urban space were summarized.

Keywords: block, space syntax and methodology, street, urban space, Yangzhou

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2119 A Proposed Plan for the Viral Marketing of Sporting Products and Services to Social Media Users in the Arab World

Authors: Ahmed F. Abdel Qader

Abstract:

Viral marketing has resulted in a lot of excitement recently as a novel technology in the field of marketing. The need of porting institutions to attract new customers for sporting products and services has increased, especially as many international and Arab clubs rely on them for most of their funding. These organizations, especially clubs, have outlets for selling their products and services; therefore, they are in need for new approaches that are related to modern communication and innovative distribution methods that can depend on the present audience in conveying e-ads to other users in light of the increase in social media users in the Arab world. This study aims at developing a marketing plan for sporting products and services through viral marketing of social media users. The researcher used the descriptive method. The sample consisted of 1991 social media users in 13 Arab countries. The questionnaire consisted of five themes and 42 items. Allan Dib 'one-page marketing plan' was used to develop the sporting products and services marketing plan. The study found that participants reported watching e-ads of sporting products and services that appeared during browsing social media pages; Facebook was the most used means for receiving ads about sporting products and services; sharing the product’s ad depends on the availability of incentives; purchasing sporting products and services takes place after a recommendation by a relative or a friend; and their evaluation of sporting products and services depends on the experiences of other people. The study recommends that the proposed plan should be used in marketing sporting products and services.

Keywords: viral marketing, sporting products, social media, Arab world

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2118 Engineering Optimization Using Two-Stage Differential Evolution

Authors: K. Y. Tseng, C. Y. Wu

Abstract:

This paper employs a heuristic algorithm to solve engineering problems including truss structure optimization and optimal chiller loading (OCL) problems. Two different type algorithms, real-valued differential evolution (DE) and modified binary differential evolution (MBDE), are successfully integrated and then can obtain better performance in solving engineering problems. In order to demonstrate the performance of the proposed algorithm, this study adopts each one testing case of truss structure optimization and OCL problems to compare the results of other heuristic optimization methods. The result indicates that the proposed algorithm can obtain similar or better solution in comparing with previous studies.

Keywords: differential evolution, Truss structure optimization, optimal chiller loading, modified binary differential evolution

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2117 A Geometrical Perspective on the Insulin Evolution

Authors: Yuhei Kunihiro, Sorin V. Sabau, Kazuhiro Shibuya

Abstract:

We study the molecular evolution of insulin from the metric geometry point of view. In mathematics, and particularly in geometry, distances and metrics between objects are of fundamental importance. Using a weaker notion than the classical distance, namely the weighted quasi-metrics, one can study the geometry of biological sequences (DNA, mRNA, or proteins) space. We analyze from the geometrical point of view a family of 60 insulin homologous sequences ranging on a large variety of living organisms from human to the nematode C. elegans. We show that the distances between sequences provide important information about the evolution and function of insulin.

Keywords: metric geometry, evolution, insulin, C. elegans

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