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BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Simple SummaryDuring the long-term co-evolution of the virus and the host, even closely related vaccines may emerge with incomplete protective immunity due to the mutations or deletions of amino acids at specific antigenic sites. The mutation of PEDV was accelerated by the recombination of different strains and the mutation of the strains adapting to the environment. These mutations either cause immune escape from conventional vaccines or affect the virulence of the virus. Therefore, researching and developing new vaccines with cross-protection through continuous monitoring, isolation and sequencing are important to determine whether their genetic characteristics are changed and to evaluate the protective efficacy of current vaccines. The porcine epidemic diarrhea virus (PEDV) can cause severe piglet diarrhea or death in some herds. Genetic recombination and mutation facilitate the continuous evolution of the virus (PEDV), posing a great challenge for the prevention and control of porcine epidemic diarrhea (PED). Disease materials of piglets with PEDV vaccination failure in some areas of Shanxi, Henan and Hebei provinces of China were collected and examined to understand the prevalence and evolutionary characteristics of PEDV in these areas. Forty-seven suspicious disease materials from different litters on different farms were tested by multiplex PCR and screened by hematoxylin-eosin staining and immunohistochemistry. PEDV showed a positivity rate of 42.6%, infecting the small and large intestine and mesenteric lymph node tissues. The isolated strains infected Vero, PK-15 and Marc-145 multihost cells and exhibited low viral titers in all three cell types, as indicated by their growth kinetic curves. Possible putative recombination events in the isolates were identified by RDP4.0 software. Sequencing and phylogenetic analysis showed that compared with the classical vaccine strain, PEDV SX6 contains new insertion and mutations in the S region and belongs to genotype GIIa. Meanwhile, ORF3 has the complete amino acid sequence with aa80 mutated wild strains, compared to vaccine strains CV777, AJ1102, AJ1102-R and LW/L. These results will contribute to the development of new PEDV vaccines based on prevalent wild strains for the prevention and control of PED in China.
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Porcine sapelovirus (PSV) is an emerging swine enteric virus that can cause various disorders including acute diarrhea, respiratory distress, reproductive failure, and polioencephalomyelitis in pigs. In this study, we isolated a PSV strain HNHB-01 from a clinical porcine deltacoronavirus- (PDCoV-) positive intestinal content of a diarrheic piglet. PSV was first identified using the small RNA deep sequencing and assembly, and further identified by the electron microscopic observation and the immunofluorescence assay. Subsequently, this virus was serially passaged in swine testis (ST) cells, and the complete genomics of PSV HNHB-01 passage 5 (P5), P30, P60, and P100 were sequenced and analyzed. 9 nucleotide mutations and 7 amino acid changes occurred in the PSV HNHB-01 P100 strain when compared with the PSV HNHB-01 P5. Pathogenicity investigation showed that orally inoculation of PSV HNHB-01 P30 could cause obvious clinical symptoms and had broad tissue tropism in 5-day-old piglets. Epidemiological investigation revealed that PSV infections and the coinfections of diarrhea coronaviruses were highly prevalent in swine herds. The complete genomes of 8 representative PSV epidemic strains were sequenced and analyzed. Phylogenetic analysis revealed that the PSV epidemic strains were closely related to other PSV reference strains that located in the Chinese clade. Furthermore, recombination analysis revealed that the recombination events were occurred in downstream of the 2C region in our sequenced PSV HNNY-02/CHN/2018 strain. Our results provided theoretical basis for future research studies of the pathogenic mechanism, evolutionary characteristics, and the development of vaccines against PSV.
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The transmembrane domains of viral proteins are highly conserved and crucial to normal viral function. Oligomeric transmembrane domains present novel opportunities for drug development, as their disruption can prevent the assembly of the virus. The Reichart lab is particularly interested in developing retro-inverso peptide inhibitors. Retro-inverso peptides are peptides using D-amino acids mirroring a region of target protein, which allows the peptide to inhibit viral assembly, but they are also significantly less likely to be catabolized by natural metabolic or immunologic processes. The efficacy of these inhibitors is governed largely by the extent to which they mirror the target protein, making highly conserved regions, such as transmembrane domains, ideal target regions for these inhibitors. The primary technique in the literature for the investigation of oligomerization states uses fluorescence spectroscopy. We are now working on developing a novel alternative system to evaluate protein oligomerization using spin-labeled peptides that are directly incorporated into the peptide sequence. Direct incorporation of the spin-label into the peptide sequence is a more powerful technique than the standard procedures used in the literature. In particular, the ability to incorporate spin labels in various positions within the protein can give novel insights into the relative depth of the protein within a membrane, which is very difficult to study using other techniques and not possible using the fluorescence technique. The transmembrane domains of proteins with known and well-characterized monomer and trimer standard oligomerization states were synthesized using an Fmoc Solid- Phase Peptide Synthesis (SPPS) procedure incorporating an Fmoc-2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid, (Fmoc-TOAC) instead of an alanine. Direct incorporation of stable N-oxide spin labels, which can be contrasted to labeling cysteine residues after the protein synthesis, has been used for the investigation of the secondary structure of proteins for decades, but the application of this spin labeling technique to study the oligomerization states of transmembrane domains of proteins is an understudied application. The products of SPPS were analyzed using a Liquid Chromatography Mass Spectroscopy instrument and purified using High Performance Liquid Chromatography. The spin-label was then deprotected and evaluated using Electron Spin Resonance (ESR) Spectroscopy. There are two primary future directions following this research project: first, the generation of viral proteins with spin labels incorporated in different positions to determine the relative depth of each position within the membrane;second, the incorporation of spin labels into SARS-CoV- 2 proteins to develop a model for in vitro evaluation of retro-inverso peptide assembly inhibitors. -Hampden-Sydney College Office of Undergraduate Research.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Objective To identify the pathogen and track the genetic source of a cluster of cases with fever in a kindergarten in Fengtai district during the normalization of COVID-19 prevention and control in Beijing.Methods A descriptive analysis method was used to investigate this cluster of cases with fever in April 2021.Pharyngeal swabs were collected and viral nucleic acid was extracted, real-time PCR was performed to identify SARS-CoV-2 and other common respiratory virus. G gene of human metapneumovirus（hMPV） was amplified by RT-PCR and was then sequenced. BioEdit was used for G gene sequence analysis and the Neighbor-Joining model in MEGA 5. 0 software was used to construct the phylogenic tree of G gene. Results A total of 16 cases were reported in one class with the incidence of 53. 3%（16/30） during 8 days of a cluster outbreak. All pharyngeal swabs collected from 12 cases were tested SARS-CoV-2 negative, six were found to be hMPV positive by multiplex-PCR, and one was positive for both human adenovirus and hMPV. Full-length sequences of G genes were obtained from 2 strains of hMPV. Sequence analysis showed that both strains were hMPV B2 and the nucleic acid homology of G gene was 96. 73%-98. 01% with strains from Japan（LC337940, LC337935, LC1922349） in 2016 and over 98. 40%with strains from Shandong（OL625642, OL625644） in 2019, Henan MN944096 in 2019.Compared with the amino acid sequence of hMPV-B2 reference strain（AY297748）, six amino acid insertions containing EKEKEK were identified between 161-166 amino acid location and N-glycosylation of G protein analysis showed that the two strains had four N-glycosylation sites. Conclusions The leading pathogen for this cluster outbreak is found to be hMPV-B2, which are highly homologous with strains from Japan, Shandong and Henan. Therefore, a non-stop surveillance of hMPV is necessary during the normalization control and prevention period for COVID-19.
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The application of machine learning in the medical field is still limited. The main reason behind the lack of use is the unavailability of an easy-to-use machine learning system that targets non-technical users. The objective of this paper is to propose an automated machine learning system to aid non-technical users. The proposed system provides the user with simple choices to provide suggestions to the system. The system uses the combination of the user's choices and performance evaluation to select the most suited model from available options. In this study, we employed the system on a Parkinson's disease dataset. The templates for support vector machine and random forest algorithms are provided to the system. Support vector machines and random forests were able to produce 80% and 75% accuracy, respectively. The system used performance parameters of the system and user choices to select the most suited models for each test case. The support vector machine was selected as the most suited model in three test cases, while random forest was selected as the most suited for one test case. The test cases also showed that the weighted time parameter impacted the results heavily.Copyright © 2022 The Author(s)
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Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that causes severe diarrhea to pigs of all ages, especially the suckling piglets under one-week-old. We previously isolated a highly pathogenic PDCoV strain, CZ2020, from a diarrheal piglet and have passaged it for over 100 passages. The adaptability of the CZ2020 increased gradually in vitro as the passage increased. Amino acid mutations were observed in pp1a, pp1ab, spike, envelop, and membrane proteins, and the spike protein accounts for 66.7% of all amino acid mutations. Then, the high passage strains, CZ2020-F80 and CZ2020-F100, were selected for evaluation of the pathogenicity in three-day-old piglets to examine whether these amino acid changes affected their virulence. At 2 days postchallenge (DPC), 2/5 piglets started to show typical diarrhea, and at 4 DPC, severe diarrhea was observed in the CZ2020-challenged piglets. Viral RNA could be detected at 1 DPC in rectal swabs and reached its highest at 4 DPC in the CZ2020-challenged group. CZ2020-F80- and CZ2020-F100-challenged groups have one piglet exhibiting mild diarrhea at 4 and 6 DPC, respectively. Compared with the CZ2020-challenged group, the piglets in CZ2020-F80- and F100-challenged groups had lower viral loads in rectal swabs, intestines, and other organs. No obvious histopathological lesions were observed in the intestines of CZ2020-F80- and F100-challenged piglets. Virulent PDCoV infection could also induce strong interferons and proinflammatory cytokines in vitro and in vivo. These data indicate that the strains, CZ2020-F80 and CZ2020-F100, were significantly attenuated via serial passaging in vitro and have the potential for developing attenuated vaccine candidates.
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The strategy of drug repurposing has been proved successful in response to the current corona-virus pandemic, with remdesivir becoming the first drug of choice, an antiviral drug approved for the treatment of COVID-19. In parallel to this, several drugs, such as antimalarial, corticosteroids, and antibi-otics, like azithromycin, are used to treat the severe condition of hospitalized COVID-19 patients, while clinical testing of additional therapeutic drugs, including vaccines, is going on. It is reasonably expected that this review article will deliver optimized and specific curative tools that will increase the attentive-ness of health systems to the probable outlook of epidemics in the future. This review focuses on the ap-plication of repurposed drugs by studying their structure, pharmacokinetic study, different mechanisms of action, and Covid-19 guidelines, which can potentially influence SARS-CoV-2. For most of the drugs, direct clinical evidence regarding their effectiveness in the treatment of COVID-19 is missing. Future clinical trial studies may conclude that one of these can be more potential to inhibit the progression of COVID-19.Copyright © 2022 Bentham Science Publishers.
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The Coronavirus Disease 2019 (COVID-19), also known as a novel coronavirus (2019-n-CoV), reportedly originated from Wuhan City, Hubei Province, China. Coronavirus Disease 2019 rapidly spread all over the world within a short period. On January 30, 2020, the World Health Organization (WHO) declared it a global epidemic. COVID-19 is a Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. SARS-CoV and the Middle East Respiratory Syndrome coron-avirus (MERS-CoV) genome sequences similar identity with 2019-nCoV or Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). However, few amino acid sequences of 2019-nCoV differ from SARS-CoV and MERS-CoV. COVID-19 shares about 90% amino acid sequence simi-larity with SARS-CoV. Effective prevention methods should be taken in order to control this pandemic situation. To date, there are no effective treatments available to treat COVID-19. This review provides information regarding COVID-19 history, epidemiology, pathogenesis and molecular diagnosis. Also, we focus on the development of vaccines in the management of this COVID-19 pandemic and limiting the spread of the virus.Copyright © 2022 Bentham Science Publishers.
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Genome sequence analysis of Atlantic salmon bafinivirus (ASBV) revealed a small open reading frame (ORF) predicted to encode a Type I membrane protein with an N-terminal cleaved signal sequence (110 aa), likely an envelope (E) protein. Bioinformatic analyses showed that the predicted protein is strikingly similar to the coronavirus E protein in structure. This is the first report to identify a putative E protein ORF in the genome of members of the Oncotshavirus genus (subfamily Piscavirinae, family Tobaniviridae, order Nidovirales) and, if expressed would be the third family (after Coronaviridae and Arteriviridae) within the order to have the E protein as a major structural protein.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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Introduction: Vaccination has become a main tool in combat against coronavirus disease 2019 (COVID-19). ORF1ab (open reading frame1ab) is biggest ORF of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) genome. Moreover ORF1ab protein is early translated in infected cells. Besides ORF1ab is genetically stable and could be a valuable source of conserved epitopes appropriate to prepare effective protein vaccines for control of many SARS-CoV-2 variants. Hypersensitivity responses to SARS-CoV-2 vaccines have been reported by numerous studies. Objective(s): In this study SARS-CoV-2 ORF1ab protein allergenicity was predicted by bioinformatic. Method(s): The amino acid sequences of SARS-CoV-2 ORF1ab protein were obtained in NCBI database at www.ncbi.nlm.nih.gov in FASTA format. Next, allergenicity of the SARS-CoV-2 ORF1ab protein was evaluated with Allergen FP server V.1. Result(s): ORF1ab protein of SARS-CoV-2 was found to be an allergen as was confirmed by allergen FP server V.1. Conclusion(s): According to our data, ORF1ab protein of COVID-19 was potentially allergenic. Hypersensitivity reactions to some SARS-CoV-2 vaccines reported by various studies may be partly due to ORF1ab protein allergenicity. Meanwhile ORF1ab protein being a valuable source of conserved epitopes is suitable to make efficient protein vaccines for control of many SARS-CoV-2 variants. For preparation of safe and effective anti- SARS-CoV-2 vaccines from ORF1ab protein, recognition and elimination of its allergenic epitope (s) is necessary. Altogether immunization with an allergenically engineered ORF1ab protein might have potential implication in fighting the virus.
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Background: SARS-CoV-2 has been a topic of discussion ever since the beginning of 2020. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to the repurposing of drugs and vaccine development. The rapid data analysis and widespread tools have made bioinformatics capable of giving new insights to deal with the current scenario more efficiently through an emerging field, vaccinomics. Objective(s): The present in silico study was attempted to identify peptide fragments from spike surface glycoprotein of SARS-CoV-2 that can be efficiently used for the development of an epi-tope-based vaccine designing approach. Method(s): The epitopes of B and T-cell are predicted using integrated computational tools. VaxiJen server, NetCTL, and IEDB tools were used to study, analyze, and predict potent T-cell epitopes, their subsequent MHC-I interactions, and B-cell epitopes. The 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further made using AutoDock4.0. Result(s): Based on result interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as potential B-cell and T-cell epitopes, re-spectively. Conclusion(s): The peptide sequence WTAGAAAYY and the amino acid sequence from 1138-1145 of the spike protein of SARS-CoV-2 can be used as a probable B-cell epitope candidate. Also, the amino acid sequence YDPLQPEL can be used as a potent T-cell epitope. This in silico study will help us identify novel epitope-based peptide vaccine targets in the spike protein of SARS-CoV-2. Further, the in vitro and in vivo study needed to validate the findings.Copyright © 2022 Bentham Science Publishers.
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BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHOD(S): We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40.0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1.0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi.Copyright © 2023 Elsevier Ltd. All rights reserved.
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Background: SARS-nCOV-2 is a variant of the known SARS coronavirus family. The mutations in viruses are very rapid and can play a crucial role in the evolution or devolution of the organism. This has a direct impact on "host jumping" and the pathogenicity of the virus. Objective(s): The study aims to understand the frequency of genomic variations that have occurred in the virus affecting the Indian sub-population. The impact of variations translating to proteins and its consequences affecting protein stability and interaction were studied. Method(s): Phylogenetic analysis of the 140 genomes from the India region was performed, followed by SNP and Indel analysis of both CDS and non-CDS regions. This effort was followed by a prediction of mutations occurring in 8 proteins of interest and the impact on protein stability and prospective drug interactions. Result(s): Genomes showed variability in origin, and major branches can be mapped to the 2002 outbreak of SARS. The mutation frequency in CDS regions showed that 241 C >T, 3037 C >T, 2836 C >T, and 6312 C >A occurred in 81.5% of genomes mapping to major genes. Corresponding mutations were mapped to protein sequences. The effect of mutations occurring in spike glycoprotein, RNA dependent RNA polymerase, nsp8, nucleocapsid and 3c protease was also depicted. Conclusion(s): Whilst the mutations in spike glycoprotein showcased an increase in protein stability, the residues undergoing mutations were also a part of drug binding pockets for hydroxychloro-quine. Mutations occurring in other proteins of interest led to a decrease in protein stability. The mutations were also a part of drug binding pockets for Favipiravir, Remdesivir and Dexametha-sone. The work allows analyzing larger datasets to understand mutation patterns globally.Copyright © 2021 Bentham Science Publishers.
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Background: The scientific community has supported the medicinal flora of ancient as well as modern times in extracting chemicals, which holds therapeutic potential. In many previous studies, Amentoflavone discovered as an anti-viral agent, and it is present as a bioactive constituent in many plants of different families like Selaginellaceae, Euphorbiaceae, and Calophyllaceae. Withania somnifera (Ashwagandha) is already considered a significant anti-viral agent in traditional medicine, and it is the main source of Somniferine-A and Withanolide-B. Objective(s): In this study, phytochemicals such as withanolide-b, somniferine-a, stigmasterol, amentoflavone, and chavicine were analyzed to screen protein inhibitors, out of them;such proteins are involved in the internalization and interaction of SARS-CoV-2 with human cytological domains. This will help in developing a checkpoint for SARS-CoV-2 internalization. Method(s): Chemi-informatic tools like basic local alignment search tool (BLAST), AutoDock-vina, SwissADME, MDWeb, Molsoft, ProTox-II, and LigPlot were used to examine the action of pharmacoactive agents against SARS-CoV-2. The tools used in the study were based on the finest algorithms like artificial neural networking, machine learning, and artificial intelligence. Result(s): On the basis of binding energies less than equal to-8.5 kcal/mol, amentoflavone, stigmasterol, and somniferine-A were found to be the most effective against COVID-19 disease as these chemical agents exhibit hydrogen bond interactions and competitively inhibit major proteins (SARS-CoV-2 Spike, Human ACE-2 receptor, Human Furin protease, SARS-CoV-2 RNA binding protein) that are involved in its infection and pathogenesis. Simulation analysis provides more validity to the selection of the drug candidate Amentoflavone. ADMET properties were found to be in the feasible range for putative drug candidates. Conclusion(s): Computational analysis was successfully used for searching pharmacoactive phytochemicals like Amentoflavone, Somniferine-A, and Stigmasterol that can bring control over COVID-19 expansion. This new methodology was found to be efficient, as it reduces monetary expenditures and time consumption. Molecular wet-lab validations will provide approval for finalizing our selected drug model for controlling the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.
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This work tested the hypothesis that infection causes unexplained production of anti-centromere protein antibodies (ACA) via autoimmune cross-reactivity. To further examine the clinical origin of ACA, the overlapped peptides between human pathogens, including viruses, bacteria and fungi and centromere proteins (CENP-A, CENP-B and CENP-C) were assessed. We found a broad overlap of pathogenetic peptides with human centromere proteins. These data indicate potential immune cross-reactivity between pathogens and human centromere proteins. Additionally, the current findings corroborate a molecular and mechanistic framework for autoimmune disorders related to infection. Moreover, preliminary evidence for a potential role of infection in ACA-related autoimmune diseases was presented. © 2022 The Scandinavian Foundation for Immunology.
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Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies. To overcome these limitations, design of antibodies with a larger neutralizing breadth can be pursued. Such broadly neutralizing antibodies (bnAbs) should remain targeted to a specific epitope, yet show robustness against pathogen mutability, thereby neutralizing a higher number of antigens. This is particularly important for highly mutable pathogens, like the influenza virus and the human immunodeficiency virus (HIV). The protocol describes a method for computing the "breadth” of a given antibody, an essential aspect of antibody design. © 2023, Springer Science+Business Media, LLC, part of Springer Nature.
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Aptamers are single-stranded DNA or RNA oligonucleotides that can selectively bind to a specific target. They are generally obtained by SELEX, but the procedure is challenging and time-consuming. Moreover, the identified aptamers tend to be insufficient in stability, specificity, and affinity. Thus, only a handful of aptamers have entered the practical use stage. Recently, computational approaches have demonstrated a significant capacity to assist in the discovery of high-performance aptamers. This review discusses the advances achieved in several aspects of computational tools in this field, as well as the new progress in machine learning and deep learning, which are used in aptamer identification and optimization. To illustrate these computationally aided processes, aptamer selections against SARS-CoV-2 are discussed in detail as a case study. We hope that this review will aid and motivate researchers to develop and utilize more computational techniques to discover ideal aptamers effectively. Copyright © 2022 Elsevier B.V.
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[Display omitted] • Immunohistochemistry with magnetic core nanoparticles to isolate viruses. • The use of MALDI-MS for rapid virus detection is explained in detail. • The use of ESI-MS/MS to pinpoint host-patient crosstalk is explained in detail. • The absolute quantitative MS is explained for large-scale protein quantitation. The capabilities of bioanalytical mass spectrometry to (i) detect and differentiate viruses at the peptide level whilst maintaining high sample throughput and (ii) to provide diagnosis and prognosis for infected patients are presented as a tutorial in this work to aid analytical chemists and physicians to gain insights into the possibilities offered by current high-resolution mass spectrometry technology and bioinformatics. From (i) sampling to sample treatment;(ii) Matrix-Assisted Laser Desorption Ionization- to Electrospray Ionization -based mass spectrometry;and (iii) from clustering to peptide sequencing;a detailed step-by-step guide is provided and exemplified using SARS-CoV-2 Spike Y839 variant and the variant of concern SARS-CoV-2 Alpha (B.1.1.7 lineage), Influenza B, and Influenza A subtypes AH1N1pdm09 and AH3N2. [ FROM AUTHOR]
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This paper proposes a novel and efficient method, called S-PDB, for the analysis and classification of Spike (S) protein structures of SARS-CoV-2 and other viruses/organisms in the Protein Data Bank (PDB). The method first finds and identifies protein structures in PDB that are similar to a protein structure of interest (SARS-CoV-2 S) via a protein structure comparison tool. The amino acid (AA) sequences of identified protein structures, downloaded from PDB, and their aligned amino acids (AAA) and secondary structure elements (ASSE), that are stored in three separate datasets, are then used for the reliable detection/classification of SARS-CoV-2 S protein structures. Three classifiers are used and their performance is compared by using six evaluation metrics. Obtained results show that two classifiers for text data (Multinomial Naive Bayes and Stochastic Gradient Descent) performed better and achieved high accuracy on the dataset that contains AAA of protein structures compared to the datasets for AA and ASSE, respectively. © 2022 IEEE.