Corrigendum: Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches.

[This corrects the article DOI: 10.3389/fmicb.2023.1291868.].

Computer-aided discovery of novel SmDHODH inhibitors for schistosomiasis therapy: Ligand-based drug design, molecular docking, molecular dynamic simulations, drug-likeness, and ADMET studies.

Schistosomiasis, also known as bilharzia or snail fever, is a tropical parasitic disease resulting from flatworms of the Schistosoma genus. This often overlooked disease has significant impacts in affected regions, causing enduring morbidity, hindering child development, reducing productivity, and creating economic burdens. Praziquantel (PZQ) is currently the only treatment option for schistosomiasis. Given the potential rise of drug resistance and the limited treatment choices available, there is a need to develop more effective inhibitors for this neglected tropical disease (NTD). In view of this, quantitative structure-activity relationship studies (QSAR), molecular docking, molecular dynamics simulations, drug-likeness, and ADMET predictions were applied to 31 inhibitors of Schistosoma mansoni Dihydroorotate dehydrogenase (SmDHODH). The designed QSAR model demonstrated robust statistical parameters including an R2 of 0.911, R2adj of 0.890, Q2cv of 0.686, R2pred of 0.807, and cR2p of 0.825, confirming its robustness. Compound 26, identified as the most active derivative, emerged as a lead candidate for new potential inhibitors through ligand-based drug design. Subsequently, 12 novel compounds (26A-26L) were designed with enhanced inhibition activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding and hydrophobic interactions, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules (26A and 26L). Furthermore, drug-likeness and ADMET prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for treating schistosomiasis.

In vitro and in silico investigation of effects of antimicrobial peptides from Solanaceae plants against rice sheath blight pathogen Rhizoctinia solani.

Rhizoctonia solani, the causative agent of sheath blight disease in rice, poses a significant threat to agricultural productivity. Traditional management approaches involving chemical fungicides have been effective but come with detrimental consequences for the ecosystem. This study aimed to investigate sustainable alternatives in the form of antifungal peptides derived from Solanaceous plant species as potential agents against R. solani. Peptide extracts were obtained using an optimized antimicrobial peptide (AMP) extraction method and desalted using the solid-phase extraction technique. The antifungal potential of peptide-rich extracts from Solanum tuberosum and Capsicum annum was assessed through in vitro tests employing the agar well diffusion method. Furthermore, peptide-protein docking analysis was performed on HPEPDOCK and HDOCK server; and molecular dynamics simulations (MDS) of 100 ns period were performed using the Gromacs 2020.4. The results demonstrated significant inhibition zones for both extracts at concentrations of 100 mg/mL. Additionally, the extracts of Solanum tuberosum and Capsicum annum had minimum inhibitory concentrations of 50 mg/mL and 25 mg/mL, respectively with minimum fungicidal concentrations of 25 mg/mL. Insights into the potential mechanisms of key peptides inhibiting R. solani targets were gleaned from in-silico studies. Notably, certain AMPs exhibited favorable free energy of binding against pathogenicity-related targets, including histone demethylase, sortin nexin, and squalene synthase, in protein-peptide docking simulations. Extended molecular dynamics simulations lasting 100 ns and MM-PBSA calculations were performed on select protein-peptide complexes. AMP10 displayed the most favorable binding free energy against all target proteins, with AMP3, AMP12b, AMP6, and AMP15 also exhibiting promising results against specific targets of R. solani. These findings underscore the potential of peptide extracts from S. tuberosum and C. annum as effective antifungal agents against rice sheath blight caused by R. solani.

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions.

Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child development, diminishing productivity, and imposing economic burdens. Due to the emergence of drug resistance and limited management options, there is need to develop additional effective inhibitors for schistosomiasis. In view of this, quantitative structure-activity relationship studies, molecular docking, molecular dynamics simulations, drug-likeness and pharmacokinetics predictions were applied to 39 Schistosoma mansoni Thioredoxin Glutathione Reductase (SmTGR) inhibitors. The chosen QSAR model demonstrated robust statistical parameters, including an R2 of 0.798, R2adj of 0.767, Q2cv of 0.681, LOF of 0.930, R2test of 0.776, and cR2p of 0.746, confirming its reliability. The most active derivative (compound 40) was identified as a lead candidate for the development of new potential non-covalent inhibitors through ligand-based design. Subsequently, 12 novel compounds (40a-40l) were designed with enhanced anti-schistosomiasis activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules. Furthermore, drug-likeness and pharmacokinetics prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for the treatment of schistosomiasis.

Development of multi epitope subunit vaccines against emerging carp viruses Cyprinid herpesvirus 1 and 3 using immunoinformatics approach.

Cyprinid herpesvirus is a causative agent of a destructive disease in common and koi carp (Cyprinus carpio), which leads to substantial global financial losses in aquaculture industries. Among the strains of C. herpesvirus, C. herpesvirus 1 (CyHV-1) and C. herpesvirus 3 (CyHV-3) are known as highly pathogenic to carp fishes in Europe, Asia, and Africa. To date, no effective vaccine has been developed to combat these viruses. This study aimed to develop unique multi-epitope subunit vaccines targeting the CyHV-1 and CyHV-3 using a reverse vaccinology approach. The study began with a comprehensive literature review to identify the most critical proteins, which were then subjected to in silico analyses to predict highly antigenic epitopes. These analyses involved assessing antigenicity, transmembrane topology screening, allergenecity, toxicity, and molecular docking approaches. We constructed two multi-epitope-based vaccines incorporating a suitable adjuvant and appropriate linkers. It revealed that both the vaccines are non-toxic and immunogenic. The tertiary structures of the vaccine proteins were generated, refined, and validated to ensure their suitability. The binding affinity between the vaccine constructs and TLR3 and TLR5 receptors were assessed by molecular docking studies. Molecular dynamics simulations indicated that vaccine construct V1 exhibited greater stability with both TLR3 and TLR5 based on RMSD analysis. Hydrogen bond analysis revealed a stronger binding affinity between the vaccine constructs and TLR5 compared to TLR3. Furthermore, MM-PBSA analysis suggested that both vaccine constructs exhibited a better affinity for TLR5. Considering all aspects, the results suggest that in silico development of CyHV vaccines incorporating multiple epitopes holds promise for management of diseases caused by CyHV-1 and CyHV-3. However, further in vivo trials are highly recommended to validate the efficacies of these vaccines.

In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses.

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae.

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

Exploring risk factors and molecular targets in leukemia patients with COVID-19: a bioinformatics analysis of differential gene expression.

The molecular mechanism of COVID-19's pathogenic effects in leukemia patients is still poorly known. Our study investigated the possible disease mechanism of COVID-19 and its associated risk factors in patients with leukemia utilizing differential gene expression analysis. We also employed network-based approaches to identify molecular targets that could potentially diagnose and treat COVID-19-infected leukemia patients. Our study demonstrated a shared set of 60 genes that are expressed differentially among patients with leukemia and COVID-19. Most of these genes are expressed in blood and bone marrow tissues and are predominantly implicated in the pathogenesis of different hematologic malignancies, increasingly imperiling COVID-19 morbidity and mortality among the affected patients. Additionally, we also found that COVID-19 may influence the expression of several cancer-associated genes in leukemia patients, such as CCR7, LEF1, and 13 candidate cancer-driver genes. Furthermore, our findings reveal that COVID-19 may predispose leukemia patients to altered blood homeostasis, increase the risk of COVID-19-related liver injury, and deteriorate leukemia-associated injury and patient prognosis. Our findings imply that molecular signatures, like transcription factors, proteins such as TOP21, and 25 different microRNAs, may be potential targets for diagnosing and treating COVID-19-infected leukemia patients. Nevertheless, additional experimental studies will contribute to further validating the study's findings.

Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches.

The Varicella Zoster Virus (VZV) presents a global health challenge due to its dual manifestations of chickenpox and shingles. Despite vaccination efforts, incomplete coverage, and waning immunity lead to recurrent infections, especially in aging and immunocompromised individuals. Existing vaccines prevent chickenpox but can trigger the reactivation of shingles. To address these limitations, we propose a polyvalent multiepitope subunit vaccine targeting key envelope glycoproteins of VZV. Through bioinformatics approaches, we selected six glycoproteins that are crucial for viral infection. Epitope mapping led to the identification of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell linear (LBL) epitopes. Incorporating strong immunostimulants, we designed two vaccine constructs, demonstrating high antigenicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). Molecular docking and dynamics simulations underscored the stability and affinity of the vaccine constructs with TLRs. These findings lay the foundation for a comprehensive solution to VZV infections, addressing the challenges of incomplete immunity and shingles reactivation. By employing advanced immunoinformatics and dynamics strategies, we have developed a promising polyvalent multiepitope subunit vaccine candidate, poised to enhance protection against VZV and its associated diseases. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of VZV. This innovative approach not only contributes to VZV control but also offers insights into tailored vaccine design strategies against complex viral pathogens.

Correction: An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV).

[This corrects the article DOI: 10.1371/journal.pone.0287416.].

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV).

Human T-lymphotropic virus (HTLV), a group of retroviruses belonging to the oncovirus family, has long been associated with various inflammatory and immunosuppressive disorders. At present, there is no approved vaccine capable of effectively combating all the highly pathogenic strains of HTLV that makes this group of viruses a potential threat to human health. To combat the devastating impact of any potential future outbreak caused by this virus group, our study employed a reverse vaccinology approach to design a novel polyvalent vaccine targeting the highly virulent subtypes of HTLV. Moreover, we comprehensively analyzed the molecular interactions between the designed vaccine and corresponding Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine's stability, antigenicity, and immunogenicity. Initially, two vaccine constructs were formulated, and among them, vaccine construct-2 exhibited superior solubility and structural stability. Molecular docking analyses also revealed strong binding affinity between the vaccine construct-2 and both targeted TLR2 and TLR4. Molecular dynamics simulations demonstrated enhanced stability, compactness, and consistent hydrogen bonding within TLR-vaccine complexes, suggesting a strong binding affinity. The stability of the complexes was further corroborated by contact, free energy, structure, and MM-PBSA analyses. Consequently, our research proposes a vaccine targeting multiple HTLV subtypes, offering valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to developing effective preventive and treatment approaches against HTLV-related diseases and preventing possible outbreaks. However, future research should focus on in-depth validation through experimental studies to confirm the interactions identified in silico and to evaluate the vaccine's efficacy in relevant animal models and, eventually, in clinical trials.

Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candidaauris.

Candida auris is a serious health concern of the current world that possesses a serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistant to those drugs and some strains have already shown resistance to all three available antifungal drugs in the market. Hence, finding alternative therapies is essential for saving lives from this enemy. To make the development of new treatments easier, we conducted some in silico study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test in vivo circumstances. The complete proteome of the representative strain was retrieved, and the duplicate, non-essential, human homologous, non-metabolic, and druggable proteins were then eliminated. As a result, out of a total of 5441 C. auris proteins, we were able to isolate three proteins (XP 028890156.1, XP 028891672.1, and XP 028891858.1) that are crucial for the pathogen's survival as well as host-non-homolog, metabolic, and unrelated proteins to the human microbiome. Their subcellular locations and interactions with a large number of proteins (10 proteins) further point to them being good candidates for therapeutic targets. Following in silico docking of 29 putative antifungals of plant origin against the three proteins we chose, Caledonixanthone E, Viniferin, Glaucine, and Jatrorrhizine were discovered to be the most effective means of inhibiting those proteins since they displayed higher binding affinities (ranging from -28.97 kcal/mol to -51.99 kcal/mol) than the control fluconazole (which ranged between -28.84 kcal/mol and -41.15 kcal/mol). According to the results of MD simulations and MM-PBSA calculations, Viniferin and Caledonixanthone E are the most effective ligands for the proteins XP 028890156.1, XP 028891672.1, and XP 028891858.1. Furthermore, they were predicted to be safe and also showed proper ADME properties.

A computational approach to design a polyvalent vaccine against human respiratory syncytial virus.

Human Respiratory Syncytial Virus (RSV) is one of the leading causes of lower respiratory tract infections (LRTI), responsible for infecting people from all age groups-a majority of which comprises infants and children. Primarily, severe RSV infections are accountable for multitudes of deaths worldwide, predominantly of children, every year. Despite several efforts to develop a vaccine against RSV as a potential countermeasure, there has been no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design a multi-epitope polyvalent vaccine against two major antigenic subtypes of RSV, RSV-A and RSV-B. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The peptide vaccine was modeled, refined, and validated. Molecular docking analysis with specific Toll-like receptors (TLRs) revealed excellent interactions with suitable global binding energies. Additionally, molecular dynamics (MD) simulation ensured the stability of the docking interactions between the vaccine and TLRs. Mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Subsequent mass production of the vaccine peptide was evaluated; however, there remains a necessity for further in vitro and in vivo experiments to validate its efficacy against RSV infections.

Risk factors and actionable molecular signatures in COVID-19-associated lung adenocarcinoma and lung squamous cell carcinoma patients.

The molecular mechanism of the pathological impact of COVID-19 in lung cancer patients remains poorly understood to date. In this study, we used differential gene expression pattern analysis to try to figure out the possible disease mechanism of COVID-19 and its associated risk factors in patients with the two most common types of non-small-cell lung cancer, namely, lung adenocarcinoma and lung squamous cell carcinoma. We also used network-based approaches to identify potential diagnostic and molecular targets for COVID-19-infected lung cancer patients. Our study showed that lung cancer and COVID-19 patients share 36 genes that are expressed differently and in common. Most of these genes are expressed in lung tissues and are mostly involved in the pathogenesis of different respiratory tract diseases. Additionally, we also found that COVID-19 may affect the expression of several cancer-associated genes in lung cancer patients, such as the oncogenes JUN, TNC, and POU2AF1. Moreover, our findings suggest that COVID-19 may predispose lung cancer patients to other diseases like acute liver failure and respiratory distress syndrome. Additionally, our findings, in concert with published literature, suggest that molecular signatures, such as hsa-mir-93-5p, CCNB2, IRF1, CD163, and different immune cell-based approaches could help both diagnose and treat this group of patients. Altogether, the scientific findings of this study will help formulate appropriate management measures and guide the development of diagnostic and therapeutic measures for COVID-19-infected lung cancer patients.

Computational designing of a novel subunit vaccine for human cytomegalovirus by employing the immunoinformatics framework.

Human cytomegalovirus (HCMV) is a widespread virus that can cause serious and irreversible neurological damage in newborns and even death in children who do not have the access to much-needed medications. While some vaccines and drugs are found to be effective against HCMV, their extended use has given rise to dose-limiting toxicities and the development of drug-resistant mutants among patients. Despite half a century's worth of research, the lack of a licensed HCMV vaccine heightens the need to develop newer antiviral therapies and vaccine candidates with improved effectiveness and reduced side effects. In this study, the immunoinformatics approach was utilized to design a potential polyvalent epitope-based vaccine effective against the four virulent strains of HCMV. The vaccine was constructed using seven CD8+ cytotoxic T lymphocytes epitopes, nine CD4+ helper T lymphocyte epitopes, and twelve linear B-cell lymphocyte epitopes that were predicted to be antigenic, non-allergenic, non-toxic, fully conserved, and non-human homologous. Subsequently, molecular docking study, protein-protein interaction analysis, molecular dynamics simulation (including the root mean square fluctuation (RMSF) and root mean square deviation (RMSD)), and immune simulation study rendered promising results assuring the vaccine to be stable, safe, and effective. Finally, in silico cloning was conducted to develop an efficient mass production strategy of the vaccine. However, further in vitro and in vivo research studies on the proposed vaccine are required to confirm its safety and efficacy.Communicated by Ramaswamy H. Sarma.

Immunoinformatics Approach to Design Novel Subunit Vaccine against the Epstein-Barr Virus.

Epstein-Barr virus (EBV) is a lymphotropic virus responsible for numerous epithelial and lymphoid cell malignancies, including gastric carcinoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, and Burkitt lymphoma. Hundreds of thousands of people worldwide get infected with this virus, and in most cases, this viral infection leads to cancer. Although researchers are trying to develop potential vaccines and drug therapeutics, there is still no effective vaccine to combat this virus. In this study, the immunoinformatics approach was utilized to develop a potential multiepitope subunit vaccine against the two most common subtypes of EBV, targeting three of their virulent envelope glycoproteins. Eleven cytotoxic T lymphocyte (CTL) epitopes, 11 helper T lymphocyte (HTL) epitopes, and 10 B-cell lymphocyte (BCL) epitopes were predicted to be antigenic, nonallergenic, nontoxic, and fully conserved among the two subtypes, and nonhuman homologs were used for constructing the vaccine after much analysis. Later, further validation experiments, including molecular docking with different immune receptors (e.g., Toll-like receptors [TLRs]), molecular dynamics simulation analyses (including root means square deviation [RMSD], root mean square fluctuation [RMSF], radius of gyration [Rg], principal-component analysis [PCA], dynamic cross-correlation [DCC], definition of the secondary structure of proteins [DSSP], and Molecular Mechanics Poisson-Boltzmann Surface Area [MM-PBSA]), and immune simulation analyses generated promising results, ensuring the safe and stable response of the vaccine with specific immune receptors after potential administration within the human body. The vaccine's high binding affinity with TLRs was revealed in the docking study, and a very stable interaction throughout the simulation proved the potential high efficacy of the proposed vaccine. Further, in silico cloning was also conducted to design an efficient mass production strategy for future bulk industrial vaccine production. IMPORTANCE Epstein-Barr virus (EBV) vaccines have been developing for over 30 years, but polyphyletic and therapeutic vaccines have failed to get licensed. Our vaccine surpasses the limitations of many such vaccines and remains very promising, which is crucial because the infection rate is higher than most viral infections, affecting a whopping 90% of the adult population. One of the major identifications covers a holistic analysis of populations worldwide, giving us crucial information about its effectiveness for everyone's unique immunological system. We targeted three glycoproteins that enhance the virulence of the virus to design an epitope-based polyvalent vaccine against two different strains of EBV, type 1 and 2. Our methodology in this study is nonconventional yet swift to show effective results while designing vaccines.

Evaluating the Prognostic and Therapeutic Potentials of the Proteasome 26S Subunit, ATPase (PSMC) Family of Genes in Lung Adenocarcinoma: A Database Mining Approach.

This study explored the prognostic and therapeutic potentials of multiple Proteasome 26S Subunit, ATPase (PSMC) family of genes (PSMC1-5) in lung adenocarcinoma (LUAD) diagnosis and treatment. All the PSMCs were found to be differentially expressed (upregulated) at the mRNA and protein levels in LUAD tissues. The promoter and multiple coding regions of PSMCs were reported to be differentially and distinctly methylated, which may serve in the methylation-sensitive diagnosis of LUAD patients. Multiple somatic mutations (alteration frequency: 0.6-2%) were observed along the PSMC coding regions in LUAD tissues that could assist in the high-throughput screening of LUAD patients. A significant association between the PSMC overexpression and LUAD patients' poor overall and relapse-free survival (p < 0.05; HR: >1.3) and individual cancer stages (p < 0.001) was discovered, which justifies PSMCs as the ideal targets for LUAD diagnosis. Multiple immune cells and modulators (i.e., CD274 and IDO1) were found to be associated with the expression levels of PSMCs in LUAD tissues that could aid in formulating PSMC-based diagnostic measures and therapeutic interventions for LUAD. Functional enrichment analysis of neighbor genes of PSMCs in LUAD tissues revealed different genes (i.e., SLIRP, PSMA2, and NUDSF3) previously known to be involved in oncogenic processes and metastasis are co-expressed with PSMCs, which could also be investigated further. Overall, this study recommends that PSMCs and their transcriptional and translational products are potential candidates for LUAD diagnostic and therapeutic measure discovery.

Immunoinformatic Design of a Multivalent Peptide Vaccine Against Mucormycosis: Targeting FTR1 Protein of Major Causative Fungi.

Mucormycosis is a potentially fatal illness that arises in immunocompromised people due to diabetic ketoacidosis, neutropenia, organ transplantation, and elevated serum levels of accessible iron. The sudden spread of mucormycosis in COVID-19 patients engendered massive concern worldwide. Comorbidities including diabetes, cancer, steroid-based medications, long-term ventilation, and increased ferritin serum concentration in COVID-19 patients trigger favorable fungi growth that in turn effectuate mucormycosis. The necessity of FTR1 gene-encoded ferrous permease for host iron acquisition by fungi has been found in different studies recently. Thus, targeting the transit component could be a potential solution. Unfortunately, no appropriate antifungal vaccine has been constructed as of yet. To date, mucormycosis has been treated with antiviral therapy and surgical treatment only. Thus, in this study, the FTR1 protein has been targeted to design a convenient and novel epitope-based vaccine with the help of immunoinformatics against four different virulent fungal species. Furthermore, the vaccine was constructed using 8 CTL, 2 HTL, and 1 LBL epitopes that were found to be highly antigenic, non-allergenic, non-toxic, and fully conserved among the fungi under consideration. The vaccine has very reassuring stability due to its high pI value of 9.97, conclusive of a basic range. The vaccine was then subjected to molecular docking, molecular dynamics, and immune simulation studies to confirm the biological environment's safety, efficacy, and stability. The vaccine constructs were found to be safe in addition to being effective. Finally, we used in-silico cloning to develop an effective strategy for vaccine mass production. The designed vaccine will be a potential therapeutic not only to control mucormycosis in COVID-19 patients but also be effective in general mucormycosis events. However, further in vitro, and in vivo testing is needed to confirm the vaccine's safety and efficacy in controlling fungal infections. If successful, this vaccine could provide a low-cost and effective method of preventing the spread of mucormycosis worldwide.

COVID-19-Associated Candidiasis: Possible Patho-Mechanism, Predisposing Factors, and Prevention Strategies.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is threatening public health. A large number of affected people need to be hospitalized. Immunocompromised patients and ICU-admitted patients are predisposed to further bacterial and fungal infections, making patient outcomes more critical. Among them, COVID-19-associated candidiasis is becoming more widely recognized as a part of severe COVID-19 sequelae. While the molecular pathophysiology is not fully understood, some factors, including a compromised immune system, iron and zinc deficiencies, and nosocomial and iatrogenic transmissions, predispose COVID-19 patients to candidiasis. In this review, we discuss the existing knowledge of the virulence characteristics of Candida spp. and summarize the key concepts in the possible molecular pathogenesis. We analyze the predisposing factors that make COVID-19 patients more susceptible to candidiasis and the preventive measures which will provide valuable insights to guide the effective prevention of candidiasis in COVID-19 patients.