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1.
Sci Rep ; 11(1): 21849, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1505527

ABSTRACT

The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.


Subject(s)
Adjuvants, Immunologic/chemistry , Antigens, Archaeal/chemistry , COVID-19 Vaccines/therapeutic use , Lipids/chemistry , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Body Weight , COVID-19/therapy , Chlorocebus aethiops , Cricetinae , Cytokines/metabolism , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunization, Passive , Mesocricetus , Mice , Mice, Inbred C57BL , Neutralization Tests , Peptides/chemistry , Protein Domains , SARS-CoV-2 , Toll-Like Receptors/immunology , Vero Cells , Viral Load
2.
Sci Rep ; 11(1): 21768, 2021 11 05.
Article in English | MEDLINE | ID: covidwho-1505016

ABSTRACT

Rapid design, screening, and characterization of biorecognition elements (BREs) is essential for the development of diagnostic tests and antiviral therapeutics needed to combat the spread of viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address this need, we developed a high-throughput pipeline combining in silico design of a peptide library specific for SARS-CoV-2 spike (S) protein and microarray screening to identify binding sequences. Our optimized microarray platform allowed the simultaneous screening of ~ 2.5 k peptides and rapid identification of binding sequences resulting in selection of four peptides with nanomolar affinity to the SARS-CoV-2 S protein. Finally, we demonstrated the successful integration of one of the top peptides into an electrochemical sensor with a clinically relevant limit of detection for S protein in spiked saliva. Our results demonstrate the utility of this novel pipeline for the selection of peptide BREs in response to the SARS-CoV-2 pandemic, and the broader application of such a platform in response to future viral threats.


Subject(s)
COVID-19/immunology , Combinatorial Chemistry Techniques , Peptides/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , COVID-19/virology , Computational Biology , Electrochemistry/methods , Enzyme-Linked Immunosorbent Assay , Humans , Interferometry , Kinetics , Peptide Library , Protein Array Analysis , Protein Engineering , Saliva/immunology
3.
Nat Commun ; 12(1): 6343, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1500461

ABSTRACT

Peptide secondary metabolites are common in nature and have diverse pharmacologically-relevant functions, from antibiotics to cross-kingdom signaling. Here, we present a method to design large libraries of modified peptides in Escherichia coli and screen them in vivo to identify those that bind to a single target-of-interest. Constrained peptide scaffolds were produced using modified enzymes gleaned from microbial RiPP (ribosomally synthesized and post-translationally modified peptide) pathways and diversified to build large libraries. The binding of a RiPP to a protein target leads to the intein-catalyzed release of an RNA polymerase σ factor, which drives the expression of selectable markers. As a proof-of-concept, a selection was performed for binding to the SARS-CoV-2 Spike receptor binding domain. A 1625 Da constrained peptide (AMK-1057) was found that binds with similar affinity (990 ± 5 nM) as an ACE2-derived peptide. This demonstrates a generalizable method to identify constrained peptides that adhere to a single protein target, as a step towards "molecular glues" for therapeutics and diagnostics.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Peptides/chemistry , Peptides/pharmacology , SARS-CoV-2/drug effects , COVID-19/drug therapy , COVID-19/virology , Drug Design , Drug Evaluation, Preclinical , Humans , Kinetics , Models, Molecular , Peptides/genetics , Protein Binding , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
4.
Int J Mol Sci ; 22(21)2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1488613

ABSTRACT

The renin-angiotensin system (RAS) is a key regulator of blood pressure and hypertension. Angiotensin-converting enzyme 2 (ACE2) and angiotensin-converting enzyme I (ACE) are two main components of the RAS that play a major role in blood pressure homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 as a receptor to enter cells. Despite some controversies, numerous studies have reported a significant association between the use of ACE inhibitors and reduced risk of COVID-19. In our previous studies, we produced and identified peptide sequences present in whey hydrolysates exhibiting high ACE inhibitory activity. Therefore, the aim of this work is to obtain an improved understanding of the function of these natural peptides as RAS inhibitors and investigate their potential therapeutic role in the COVID-19 pandemic. The molecular interactions between peptides IPP, LIVTQ, IIAE, LVYPFP, and human ACE2 were assessed by employing a molecular docking approach. The results show that natural whey-derived peptides have a dual inhibitory action against both ACE and ACE2. This dual activity distinguishes these ACE inhibitory peptides from synthetic drugs, such as Captopril and Lisinopril which were not shown to inhibit ACE2 activity, and may represent a potential strategy in the treatment of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Peptides/chemistry , Peptides/pharmacology , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Peptides/metabolism , Peptidyl-Dipeptidase A/chemistry , Renin-Angiotensin System/drug effects , Whey Proteins/chemistry
5.
Int J Mol Sci ; 22(21)2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1488610

ABSTRACT

The angiotensin-converting enzyme 2 (ACE2) is the receptor used by SARS-CoV and SARS-CoV-2 coronaviruses to attach to cells via the receptor-binding domain (RBD) of their viral spike protein. Since the start of the COVID-19 pandemic, several structures of protein complexes involving ACE2 and RBD as well as monoclonal antibodies and nanobodies have become available. We have leveraged the structural data to design peptides to target the interaction between the RBD of SARS-CoV-2 and ACE2 and SARS-CoV and ACE2, as contrasting exemplar, as well as the dimerization surface of ACE2 monomers. The peptides were modelled using our original method: PiPreD that uses native elements of the interaction between the targeted protein and cognate partner(s) that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations surrogating key interactions at the interface. To facilitate the access to this information we have created a freely available and dedicated web-based repository, PepI-Covid19 database, providing convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic and diagnostic agents.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Host-Pathogen Interactions/drug effects , Peptides/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Binding Sites , Databases, Factual , Humans , Models, Molecular , Peptide Library , Peptides/chemistry , Protein Conformation , Protein Domains , Protein Engineering , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry
6.
Molecules ; 26(20)2021 Oct 13.
Article in English | MEDLINE | ID: covidwho-1470934

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, the causative agent of coronavirus disease (COVID-19)) has caused relatively high mortality rates in humans throughout the world since its first detection in late December 2019, leading to the most devastating pandemic of the current century. Consequently, SARS-CoV-2 therapeutic interventions have received high priority from public health authorities. Despite increased COVID-19 infections, a vaccine or therapy to cover all the population is not yet available. Herein, immunoinformatics and custommune tools were used to identify B and T-cells epitopes from the available SARS-CoV-2 sequences spike (S) protein. In the in silico predictions, six B cell epitopes QTGKIADYNYK, TEIYQASTPCNGVEG, LQSYGFQPT, IRGDEVRQIAPGQTGKIADYNYKLPD, FSQILPDPSKPSKRS and PFAMQMAYRFNG were cross-reacted with MHC-I and MHC-II T-cells binding epitopes and selected for vaccination in experimental animals for evaluation as candidate vaccine(s) due to their high antigenic matching and conserved score. The selected six peptides were used individually or in combinations to immunize female Balb/c mice. The immunized mice raised reactive antibodies against SARS-CoV-2 in two different short peptides located in receptor binding domain and S2 region. In combination groups, an additive effect was demonstrated in-comparison with single peptide immunized mice. This study provides novel epitope-based peptide vaccine candidates against SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/chemistry , COVID-19/prevention & control , Epitopes, B-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/chemistry , SARS-CoV-2/metabolism , Amino Acid Sequence , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/metabolism , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/metabolism , Female , Humans , Immunization , Mice , Mice, Inbred BALB C , Peptides/chemistry , Peptides/immunology , Peptides/metabolism , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
7.
Int J Mol Sci ; 22(20)2021 Oct 18.
Article in English | MEDLINE | ID: covidwho-1470894

ABSTRACT

Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as "cytokine storm", which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions.


Subject(s)
Acute Lung Injury/pathology , Cytokines/chemistry , Peptides/metabolism , Receptors, Tumor Necrosis Factor, Type I/metabolism , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Acute Lung Injury/metabolism , Animals , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/pharmacology , Lung/metabolism , Lung/pathology , Lymphocyte Activation/drug effects , Male , Mice , Mice, Inbred ICR , Peptides/chemistry , Peptides/pharmacology , Protein Binding , Receptors, Tumor Necrosis Factor, Type I/antagonists & inhibitors , Triggering Receptor Expressed on Myeloid Cells-1/antagonists & inhibitors
8.
Int J Mol Sci ; 22(20)2021 Oct 18.
Article in English | MEDLINE | ID: covidwho-1470893

ABSTRACT

SputnikV is a vaccine against SARS-CoV-2 developed by the Gamaleya National Research Centre for Epidemiology and Microbiology. The vaccine has been shown to induce both humoral and cellular immune responses, yet the mechanisms remain largely unknown. Forty SputnikV vaccinated individuals were included in this study which aimed to demonstrate the location of immunogenic domains of the SARS-CoV-2 S protein using an overlapping peptide library. Additionally, cytokines in the serum of vaccinated and convalescent COVID-19 patients were analyzed. We have found antibodies from both vaccinated and convalescent sera bind to immunogenic regions located in multiple domains of SARS-CoV-2 S protein, including Receptor Binding Domain (RBD), N-terminal Domain (NTD), Fusion Protein (FP) and Heptad Repeats (HRs). Interestingly, many peptides were recognized by immunized and convalescent serum antibodies and correspond to conserved regions in circulating variants of SARS-CoV-2. This breadth of reactivity was still evident 90 days after the first dose of the vaccine, showing that the vaccine has induced a prolonged response. As evidenced by the activation of T cells, cellular immunity strongly suggests the high potency of the SputnikV vaccine against SARS-CoV-2 infection.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunity, Cellular , Immunity, Humoral , Adult , Amino Acid Sequence , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cytokines/metabolism , Female , Humans , Male , Peptides/chemistry , Peptides/immunology , Principal Component Analysis , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/cytology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccination
9.
Cells ; 10(10)2021 10 14.
Article in English | MEDLINE | ID: covidwho-1470797

ABSTRACT

Prediction of linear B cell epitopes is of interest for the production of antigen-specific antibodies and the design of peptide-based vaccines. Here, we present BCEPS, a web server for predicting linear B cell epitopes tailored to select epitopes that are immunogenic and capable of inducing cross-reactive antibodies with native antigens. BCEPS implements various machine learning models trained on a dataset including 555 linearized conformational B cell epitopes that were mined from antibody-antigen protein structures. The best performing model, based on a support vector machine, reached an accuracy of 75.38% ± 5.02. In an independent dataset consisting of B cell epitopes retrieved from the Immune Epitope Database (IEDB), this model achieved an accuracy of 67.05%. In BCEPS, predicted epitopes can be ranked according to properties such as flexibility, accessibility and hydrophilicity, and with regard to immunogenicity, as judged by their predicted presentation by MHC II molecules. BCEPS also detects if predicted epitopes are located in ectodomains of membrane proteins and if they possess N-glycosylation sites hindering antibody recognition. Finally, we exemplified the use of BCEPS in the SARS-CoV-2 Spike protein, showing that it can identify B cell epitopes targeted by neutralizing antibodies.


Subject(s)
COVID-19/prevention & control , Computational Biology/methods , Databases, Factual , Epitopes, B-Lymphocyte/chemistry , SARS-CoV-2 , Animals , Antigens , COVID-19/immunology , Cross Reactions , Glycosylation , Histocompatibility Antigens Class II , Humans , Hydrophobic and Hydrophilic Interactions , Internet , Machine Learning , Mice , Peptides/chemistry , Protein Domains , Proteins/chemistry , Reproducibility of Results , Software , Spike Glycoprotein, Coronavirus/chemistry
11.
ACS Appl Mater Interfaces ; 13(41): 48469-48477, 2021 Oct 20.
Article in English | MEDLINE | ID: covidwho-1461961

ABSTRACT

The COVID-19 pandemic highlighted the importance of developing surfaces and coatings with antiviral activity. Here, we present, for the first time, peptide-based assemblies that can kill viruses. The minimal inhibitory concentration (MIC) of the assemblies is in the range tens of micrograms per milliliter. This value is 2 orders of magnitude smaller than the MIC of metal nanoparticles. When applied on a surface, by drop casting, the peptide spherical assemblies adhere to the surface and form an antiviral coating against both RNA- and DNA-based viruses including coronavirus. Our results show that the coating reduced the number of T4 bacteriophages (DNA-based virus) by 3 log, compared with an untreated surface and 6 log, when compared with a stock solution. Importantly, we showed that this coating completely inactivated canine coronavirus (RNA-based virus). This peptide-based coating can be useful wherever sterile surfaces are needed to reduce the risk of viral transmission.


Subject(s)
Antiviral Agents/chemistry , Peptides/chemistry , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Bacteriophages/drug effects , COVID-19/drug therapy , COVID-19/virology , Coronavirus/drug effects , Coronavirus/isolation & purification , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Dihydroxyphenylalanine/chemistry , Dog Diseases/drug therapy , Dog Diseases/virology , Dogs , Humans , Metal Nanoparticles/chemistry , Peptides/pharmacology , Peptides/therapeutic use , SARS-CoV-2/isolation & purification , Virus Inactivation/drug effects
12.
Eur J Med Chem ; 227: 113910, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1458683

ABSTRACT

The current COVID-19 epidemic has greatly accelerated the application of mRNA technology to our real world, and during this battle mRNA has proven it's unique advantages compared to traditional biopharmaceutical and vaccine technology. In order to overcome mRNA instability in human physiological environments, mRNA chemical modifications and nano delivery systems are two key factors for their in vivo applications. In this review, we would like to summarize the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in innovative materials and delivery strategies. The nano delivery systems include lipid delivery systems (lipid nanoparticles and liposomes), polymer complexes, micelles, cationic peptides and so on. The similarities and differences of lipid nanoparticles and liposomes are also discussed. In addition, this review also present the applications of mRNA to other areas than COVID-19 vaccine, such as infectious diseases, tumors, and cardiovascular disease, for which a variety of candidate vaccines or drugs have entered clinical trials. Furthermore, mRNA was found that it might be used to treat some genetic disease, overcome the immaturity of the immune system due to the small fetal size in utero, treat some neurological diseases that are difficult to be treated surgically, even be used in advancing the translation of iPSC technology et al. In short, mRNA has a wide range of applications, and its era has just begun.


Subject(s)
/chemistry , RNA, Messenger/chemistry , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/chemistry , Humans , Liposomes/chemistry , Micelles , Nanoparticles/chemistry , Peptides/chemistry , RNA, Messenger/metabolism , SARS-CoV-2/isolation & purification
13.
Cells ; 10(10)2021 10 03.
Article in English | MEDLINE | ID: covidwho-1444119

ABSTRACT

The data currently available on how the immune system recognises the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus; however, we lack data on how T cells are able to recognise this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.


Subject(s)
COVID-19/immunology , COVID-19/virology , Epitopes, T-Lymphocyte/chemistry , HLA-A2 Antigen/immunology , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , CD8-Positive T-Lymphocytes/cytology , Crystallography, X-Ray , Cytokines/metabolism , Epitopes/chemistry , HLA-A2 Antigen/chemistry , Humans , Mutation , Peptides/chemistry , Protein Binding , Protein Denaturation , Protein Folding , Surface Plasmon Resonance , T-Lymphocytes, Cytotoxic/immunology
14.
Front Immunol ; 12: 714177, 2021.
Article in English | MEDLINE | ID: covidwho-1444042

ABSTRACT

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources ("cytokine storm"). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Chorionic Gonadotropin/therapeutic use , Peptides/therapeutic use , Sepsis/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/metabolism , Bacteria/metabolism , Chorionic Gonadotropin/chemistry , Chorionic Gonadotropin/metabolism , Cytokine Release Syndrome/drug therapy , Glycoproteins/chemistry , Glycoproteins/metabolism , Humans , Inflammation , Peptides/chemistry , Peptides/metabolism
15.
J Comput Chem ; 42(32): 2283-2293, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1441999

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for this viral pathogen due to their efficacy, safety, and specificity. In this study, seventeen antiviral peptides which were known to inhibit SARS-CoV-1 are collected and computationally screened against heptad repeat 1 (HR1) of the SARS-CoV-2 spike protein (S2). Out of 17 peptides, Fp13 and Fp14 showed better binding affinity toward HR1 compared to a control peptide EK1 (a modified pan-coronavirus fusion inhibitor) in molecular docking. To explore the time-dependent interactions of the fusion peptide with HR1, molecular dynamics simulation was performed incorporating lipid membrane. During 100 ns MD simulation, structural and energy parameters of Fp13-HR1 and Fp14-HR1 complexes demonstrated lower fluctuations compared to the control EK1-HR1 complex. Furthermore, principal component analysis and free energy landscape study revealed that these two peptides (Fp13 and Fp14) strongly bind to the HR1 with higher affinity than that of control EK1. Tyr917, Asn919, Gln926, lys933, and Gln949 residues in HR1 protein were found to be crucial residues for peptide interaction. Notably, Fp13, Fp14 showed reasonably better binding free energy and hydrogen bond contribution than that of EK1. Taken together, Fp13 and Fp14 peptides may be highly specific for HR1 which can potentially prevent the formation of the fusion core and could be further developed as therapeutics for treatment or prophylaxis of SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/pharmacology , Peptides/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , Humans , Microbial Sensitivity Tests , Peptides/chemistry , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism
16.
J Med Chem ; 64(19): 14887-14894, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1428719

ABSTRACT

Antiviral treatments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been extensively pursued to conquer the pandemic. To inhibit the viral entry to the host cell, we designed and obtained three peptide sequences via quartz crystal microbalance measurement screening, which showed high affinity at nanomole to the S1 subunit of the spike protein and wild-type SARS-CoV-2 pseudovirus. Circular dichroism spectroscopy measurements revealed significant conformation changes of the S1 protein upon encounter with the three peptides. The peptides were able to effectively block the infection of a pseudovirus to 50% by inhibiting the host cell lines binding with the S1 protein, evidenced by the results from Western blotting and pseudovirus luciferase assay. Moreover, the combination of the three peptides could increase the inhibitory rate to 75%. In conclusion, the three chemically synthetic neutralizing peptides and their combinations hold promising potential as effective therapeutics in the prevention and treatment of COVID-19.


Subject(s)
Peptides/metabolism , Spike Glycoprotein, Coronavirus/metabolism , A549 Cells , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/virology , Cell Survival/drug effects , Circular Dichroism , Humans , Neutralization Tests , Peptides/chemistry , Peptides/pharmacology , Protein Binding , Protein Subunits/chemistry , Protein Subunits/metabolism , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Virus Internalization/drug effects
18.
Microb Pathog ; 160: 105189, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401715

ABSTRACT

The outbreak of the novel coronavirus (COVID-19) has affected millions of lives and it is one of the deadliest viruses ever known and the effort to find a cure for COVID-19 has been very high. The purpose of the study was to investigate the anti-COVID effect from the peptides derived from microalgae. The peptides from microalgae exhibit antimicrobial, anti-allergic, anti-hypersensitive, anti-tumor and immune-modulatory properties. In the In silico study, 13 cyanobacterial specific peptides were retrieved based on the extensive literature survey and their structures were predicted using Discovery Studios Visualizer. The spike protein of the novel COVID19 was retrieved from PDB (6LU7) and further molecular docking was done with the peptides through CDOCKER. The five peptides were bound clearly to the spike protein (SP) and their inhibitory effect towards the SP was promising among 13 peptides were investigated. Interestingly, LDAVNR derived from S.maxima have excellent binding and interaction energy showed -113.456 kcal/mol and -71.0736 kcal/mol respectively to target SP of COVID. The further investigation required for the in vitro confirmation of anti-COVID from indigenous microalgal species for the possible remedy in the pandemic.


Subject(s)
Antiviral Agents/chemistry , Microalgae , Peptides/chemistry , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Computer Simulation , Microalgae/chemistry , Molecular Docking Simulation
19.
Protein J ; 40(6): 799-841, 2021 12.
Article in English | MEDLINE | ID: covidwho-1401053

ABSTRACT

As expected, several new variants of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) emerged and have been detected around the world throughout this Coronavirus Disease of 2019 (COVID-19) pandemic. Currently, there is no specific developed drug against COVID-19 and the challenge of developing effective antiviral strategies based on natural agents with different mechanisms of action becomes an urgent need and requires identification of genetic differences among variants. Such data is used to improve therapeutics to combat SARS-CoV-2 variants. Nature is known to offer many biotherapeutics from animal venoms, algae and plant that have been historically used in traditional medicine. Among these bioresources, snake venom displays many bioactivities of interest such as antiviral, antiplatelet, antithrombotic, anti-inflammatory, antimicrobial and antitumoral. COVID-19 is a viral respiratory sickness due to SARS-CoV-2 which induces thrombotic disorders due to cytokine storm, platelet hyperactivation and endothelial dysfunction. This review aims to: (1) present an overview on the infection, the developed thrombo-inflammatory responses and mechanisms of induced thrombosis of COVID-19 compared to other similar pathogenesis; (2) underline the role of natural compounds such as anticoagulant, antiplatelet and thrombolytic agents; (3) investigate the management of coagulopathy related to COVID-19 and provide insight on therapeutic such as venom compounds. We also summarize the updated advances on antiviral proteins and peptides derived from snake venoms that could weaken coagulopathy characterizing COVID-19.


Subject(s)
COVID-19/drug therapy , Peptides/therapeutic use , SARS-CoV-2/drug effects , Snake Venoms/therapeutic use , Anticoagulants/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/pathology , COVID-19/virology , Humans , Pandemics , Peptides/chemistry , SARS-CoV-2/pathogenicity , Snake Venoms/chemistry
20.
Biomed Res Int ; 2021: 9998420, 2021.
Article in English | MEDLINE | ID: covidwho-1398744

ABSTRACT

The global burden of viral infection, especially the current pandemics of SARS-CoV-2, HIV/AIDS, and hepatitis, is a very risky one. Additionally, HCV expresses the necessity for antiviral therapeutic elements. Venoms are known to contain an array of bioactive peptides that are commonly used in the treatment of various medical issues. Several peptides isolated from scorpion venom have recently been proven to possess an antiviral activity against several viral families. The aim of this review is to provide an up-to-date overview of scorpion antiviral peptides and to discuss their modes of action and potential biomedical application against different viruses.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Peptides/pharmacology , Scorpion Venoms/chemistry , Virus Diseases/drug therapy , Animals , Coronavirus/drug effects , HIV-1/drug effects , Hepatitis Viruses/drug effects , Herpesvirus 1, Human/drug effects , Humans , Measles virus/drug effects , Peptides/chemistry , Peptides/isolation & purification , Virus Diseases/virology
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