Designing a Multi-epitope Vaccine against the SARS-CoV-2 Variant Based on an Immunoinformatics Approach.

BACKGROUND: SARS-CoV-2 is a life-threatening virus in the world. Scientific evidence indicates that this pathogen will emerge again in the future. Although the current vaccines have a pivotal role in the control of this pathogen, the emergence of new variants has a negative impact on their effectiveness. OBJECTIVE: Therefore, it is urgent to consider the protective and safe vaccine against all sub-coronavirus species and variants based on the conserved region of the virus. Multi-epitope peptide vaccine (MEV), comprised of immune-dominant epitopes, is designed by immunoinformatic tools and it is a promising strategy against infectious diseases. METHODS: Spike glycoprotein and nucleocapsid proteins from all coronavirus species and variants were aligned and the conserved region was selected. Antigenicity, toxicity, and allergenicity of epitopes were checked by a proper server. To robust the immunity of the multi-epitope vaccine, cholera toxin b (CTB) and three HTL epitopes of tetanus toxin fragment C (TTFrC) were linked at the N-terminal and C-terminal of the construct, respectively. Selected epitopes with MHC molecules and the designed vaccines with Toll-like receptors (TLR-2 and TLR-4) were docked and analyzed. The immunological and physicochemical properties of the designed vaccine were evaluated. The immune responses to the designed vaccine were simulated. Furthermore, molecular dynamic simulations were performed to study the stability and interaction of the MEV-TLRs complexes during simulation time by NAMD (Nanoscale molecular dynamic) software. Finally, the codon of the designed vaccine was optimized according to Saccharomyces boulardii. RESULTS: The conserved regions of spike glycoprotein and nucleocapsid protein were gathered. Then, safe and antigenic epitopes were selected. The population coverage of the designed vaccine was 74.83%. The instability index indicated that the designed multi-epitope was stable (38.61). The binding affinity of the designed vaccine to TLR2 and TLR4 was -11.4 and -11.1, respectively. The designed vaccine could induce humoral and cellular immunity. CONCLUSION: In silico analysis showed that the designed vaccine is a protective multi-epitope vaccine against SARS-CoV-2 variants.

Co-infection of COVID-19 and parasitic diseases: A systematic review.

Co-infection of COVID-19 with other diseases increases the challenges related to its treatment management. COVID-19 co-infection with parasites is studied with low frequency. Here, we systematically reviewed the cases of parasitic disease co-infection with COVID-19. All articles on COVID-19 co-infected with parasites (protozoa, helminths, and ectoparasites), were screened through defined inclusion/exclusion criteria. Of 2190 records, 35 studies remained for data extraction. The majority of studies were about COVID-19 co-infected with malaria, followed by strongyloidiasis, amoebiasis, chagas, filariasis, giardiasis, leishmaniasis, lophomoniasis, myiasis, and toxoplasmosis. No or low manifestation differences were reported between the co-infected cases and naïve COVID-19 or naïve parasitic disease. Although there was a relatively low number of reports on parasitic diseases-COVID-19 co-infection, COVID-19 and some parasitic diseases have overlapping symptoms and also COVID-19 conditions and treatment regimens may cause some parasites re-emergence, relapse, or re-activation. Therefore, more attention should be paid to the on-time diagnosis of COVID-19 and the co-infected parasites.

Co-infection of COVID-19 and parasitic diseases: A systematic review

Co-infection of COVID-19 with other diseases increases the challenges related to its treatment management. COVID-19 co-infection with parasites is studied with low frequency. Here, we systematically reviewed the cases of parasitic disease co-infection with COVID-19. All articles on COVID-19 co-infected with parasites (protozoa, helminths, and ectoparasites), were screened through defined inclusion/exclusion criteria. Of 2190 records, 35 studies remained for data extraction. The majority of studies were about COVID-19 co-infected with malaria, followed by strongyloidiasis, amoebiasis, chagas, filariasis, giardiasis, leishmaniasis, lophomoniasis, myiasis, and toxoplasmosis. No or low manifestation differences were reported between the co-infected cases and naïve COVID-19 or naïve parasitic disease. Although there was a relatively low number of reports on parasitic diseases-COVID-19 co-infection, COVID-19 and some parasitic diseases have overlapping symptoms and also COVID-19 conditions and treatment regimens may cause some parasites re-emergence, relapse, or re-activation. Therefore, more attention should be paid to the on-time diagnosis of COVID-19 and the co-infected parasites.

Immunoinformatics-aided design of a new multi-epitope vaccine adjuvanted with domain 4 of pneumolysin against Streptococcus pneumoniae strains.

BACKGROUND: Streptococcus pneumoniae (Pneumococcus) has remained a leading cause of fatal infections such as pneumonia, meningitis, and sepsis. Moreover, this pathogen plays a major role in bacterial co-infection in patients with life-threatening respiratory virus diseases such as influenza and COVID-19. High morbidity and mortality in over one million cases, especially in very young children and the elderly, are the main motivations for pneumococcal vaccine development. Due to the limitations of the currently marketed polysaccharide-based vaccines, non-serotype-specific protein-based vaccines have received wide research interest in recent years. One step further is to identify high antigenic regions within multiple highly-conserved proteins in order to develop peptide vaccines that can affect various stages of pneumococcal infection, providing broader serotype coverage and more effective protection. In this study, immunoinformatics tools were used to design an effective multi-epitope vaccine in order to elicit neutralizing antibodies against multiple strains of pneumococcus. RESULTS: The B- and T-cell epitopes from highly protective antigens PspA (clades 1-5) and PhtD were predicted and immunodominant peptides were linked to each other with proper linkers. The domain 4 of Ply, as a potential TLR4 agonist adjuvant candidate, was attached to the end of the construct to enhance the immunogenicity of the epitope vaccine. The evaluation of the physicochemical and immunological properties showed that the final construct was stable, soluble, antigenic, and non-allergenic. Furthermore, the protein was found to be acidic and hydrophilic in nature. The protein 3D-structure was built and refined, and the Ramachandran plot, ProSA-web, ERRAT, and Verify3D validated the quality of the final model. Molecular docking analysis showed that the designed construct via Ply domain 4 had a strong interaction with TLR4. The structural stability of the docked complex was confirmed by molecular dynamics. Finally, codon optimization was performed for gene expression in E. coli, followed by in silico cloning in the pET28a(+) vector. CONCLUSION: The computational analysis of the construct showed acceptable results, however, the suggested vaccine needs to be experimentally verified in laboratory to ensure its safety and immunogenicity.

Recent Patents and FDA-Approved Drugs Based on Antiviral Peptides and Other Peptide-Related Antivirals.

In spite of existing cases of severe viral infections with a high mortality rate, there are not enough antiviral drugs and vaccines available for the prevention and treatment of such diseases. In addition, the increasing reports of the emergence of viral epidemics highlight, the need for novel molecules with antiviral potential. Antimicrobial peptides (AMPs) with antiviral activity or antiviral peptides (AVPs) have turned into a research hotspot and already show tremendous potential to become pharmaceutically available antiviral medicines. AMPs, a diverse group of bioactive peptides act as a part of our first line of defense against pathogen inactivation. Although most of the currently reported AMPs are either antibacterial or antifungal peptides, the number of antiviral peptides is gradually increasing. Some of the AMPs that are shown as effective antivirals have been deployed against viruses such as influenza A virus, severe acute respiratory syndrome coronavirus (SARS-CoV), HIV, HSV, West Nile Virus (WNV), and other viruses. This review offers an overview of AVPs that have been approved within the past few years and will set out a few of the most essential patents and their usage within the context mentioned above during 2000-2020. Moreover, the present study will explain some of the progress in antiviral drugs based on peptides and peptide-related antivirals.

In silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant.

BACKGROUND: Streptococcus pneumoniae is the leading reason for invasive diseases including pneumonia and meningitis, and also secondary infections following viral respiratory diseases such as flu and COVID-19. Currently, serotype-dependent vaccines, which have several insufficiency and limitations, are the only way to prevent pneumococcal infections. Hence, it is plain to need an alternative effective strategy for prevention of this organism. Protein-based vaccine involving conserved pneumococcal protein antigens with different roles in virulence could provide an eligible alternative to existing vaccines. METHODS: In this study, PspC, PhtD and PsaA antigens from pneumococcus were taken to account to predict B-cell and helper T-cell epitopes, and epitope-rich regions were chosen to build the construct. To enhance the immunogenicity of the epitope-based vaccine, a truncated N-terminal fragment of pneumococcal endopeptidase O (PepO) was used as a potential TLR2/4 agonist which was identified by molecular docking studies. The ultimate construct was consisted of the chosen epitope-rich regions, along with the adjuvant role (truncated N-PepO) and suitable linkers. RESULTS: The epitope-based vaccine was assessed as regards physicochemical properties, allergenicity, antigenicity, and toxicity. The 3D structure of the engineered construct was modeled, refined, and validated. Molecular docking and simulation of molecular dynamics (MD) indicated the proper and stable interactions between the vaccine and TLR2/4 throughout the simulation periods. CONCLUSIONS: For the first time this work presents a novel vaccine consisting of epitopes of PspC, PhtD, and PsaA antigens which is adjuvanted with a new truncated domain of PepO. The computational outcomes revealed that the suggested vaccine could be deemed an efficient therapeutic vaccine for S. pneumoniae; nevertheless, in vitro and in vivo examinations should be performed to prove the potency of the candidate vaccine.

COVID-19: A systematic review and update on prevention, diagnosis, and treatment.

Since the rapid onset of the COVID-19 or SARS-CoV-2 pandemic in the world in 2019, extensive studies have been conducted to unveil the behavior and emission pattern of the virus in order to determine the best ways to diagnosis of virus and thereof formulate effective drugs or vaccines to combat the disease. The emergence of novel diagnostic and therapeutic techniques considering the multiplicity of reports from one side and contradictions in assessments from the other side necessitates instantaneous updates on the progress of clinical investigations. There is also growing public anxiety from time to time mutation of COVID-19, as reflected in considerable mortality and transmission, respectively, from delta and Omicron variants. We comprehensively review and summarize different aspects of prevention, diagnosis, and treatment of COVID-19. First, biological characteristics of COVID-19 were explained from diagnosis standpoint. Thereafter, the preclinical animal models of COVID-19 were discussed to frame the symptoms and clinical effects of COVID-19 from patient to patient with treatment strategies and in-silico/computational biology. Finally, the opportunities and challenges of nanoscience/nanotechnology in identification, diagnosis, and treatment of COVID-19 were discussed. This review covers almost all SARS-CoV-2-related topics extensively to deepen the understanding of the latest achievements (last updated on January 11, 2022).

Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2.

Introduction: There are currently no specific drugs and universal vaccines for Coronavirus disease 2019 (COVID-19), hence urgent effective measures are needed to discover and develop therapeutic agents. Applying peptide therapeutics and their related compounds is a promising strategy to achieve this goal. This review is written based on the literature search using several databases, previous studies, scientific reports, our current knowledge about the antimicrobial peptides (AMPs), and our personal analyses on the potential of the antiviral peptides for the treatment of COVID-19.Areas covered: In this review, we begin with a brief description of SARS-CoV2 followed by a comprehensive description of antiviral peptides (AVPs) including natural and synthetic AMPs or AVPs and peptidomimetics. Subsequently, the structural features, mechanisms of action, limitations, and therapeutic applications of these peptides are explained.Expert opinion: Regarding the lack and the limitations of drugs against COVID-19, AMPs, AVPs, and other peptide-like compounds such as peptidomimetics have captured the attention of researchers due to their potential antiviral activities. Some of these compounds comprise unique properties and have demonstrated the potential to fight SARS-CoV2, particularly melittin, lactoferrin, enfuvirtide, and rupintrivir that have the potential to enter animal and clinical trials for the treatment of COVID-19.

Enfuvirtide, an HIV-1 fusion inhibitor peptide, can act as a potent SARS-CoV-2 fusion inhibitor: an in silico drug repurposing study.

Regarding the urgency of therapeutic measures for coronavirus disease 2019 (COVID-19) pandemic, the use of available drugs with FDA approval is preferred because of the less time and cost required for their development. In silico drug repurposing is an accurate way to speed up the screening of the existing FDA-approved drugs to find a therapeutic option for COVID-19. The similarity in SARS-CoV-2 and HIV-1 fusion mechanism to host cells can be a key point for Inhibit SARS-CoV-2 entry into host cells by HIV fusion inhibitors. Accordingly, in this study, an HIV-1 fusion inhibitor called Enfuvirtide (Enf) was selected. The affinity and essential residues involving in the Enf binding to the S2 protein of SARS-CoV-2, HIV-1 gp41 protein and angiotensin-converting enzyme 2 (ACE-2) as a negative control, was evaluated using molecular docking. Eventually, Enf-S2 and Enf-gp41 protein complexes were simulated by molecular dynamics (MD) in terms of binding affinity and stability. Based on the most important criteria such as docking score, cluster size, energy and dissociation constant, the strongest interaction was observed between Enf with the S2 protein. In addition, MD results confirmed that Enf-S2 protein interaction was remarkably stable and caused the S2 protein residues to undergo the fewest fluctuations. In conclusion, it can be stated that Enf can act as a strong SARS-CoV-2 fusion inhibitor and demonstrates the potential to enter the clinical trial phase of COVID-19. Communicated by Ramaswamy H. Sarma.