Nanotechnology and COVID-19 Convergence: Toward New Planetary Health Interventions Against the Pandemic.

COVID-19 is a systemic disease affecting multiple organ systems and caused by infection with the SARS-CoV-2 virus. Two years into the COVID-19 pandemic and after the introduction of several vaccines, the pandemic continues to evolve in part owing to global inequities in access to preventive and therapeutic measures. We are also witnessing the introduction of antivirals against COVID-19. Against this current background, we review the progress made with nanotechnology-based approaches such as nanoformulations to combat the multiorgan effects of SARS-CoV-2 infection from a systems medicine lens. While nanotechnology has previously been widely utilized in the antiviral research domain, it has not yet received the commensurate interest in the case of COVID-19 pandemic response strategies. Notably, SARS-CoV-2 and nanomaterials are similar in size ranging from 50 to 200 nm. Nanomaterials offer the promise to reduce the side effects of antiviral drugs, codeliver multiple drugs while maintaining stability in the biological milieu, and sustain the release of entrapped drug(s) for a predetermined time period, to name but a few conceivable scenarios, wherein nanotechnology can enable and empower preventive medicine and therapeutic innovations against SARS-CoV-2. We conclude the article by underlining that nanotechnology-based interventions warrant further consideration to enable precision planetary health responses against the COVID-19 pandemic.

Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.

Emerging bio-contaminants such as viruses have affected health and environment settings of every country. Viruses are the minuscule entities resulting in severe contagious diseases like SARS, MERS, Ebola, and avian influenza. Recent epidemic like the SARS-CoV-2, the virus has undergone mutations strengthen them and allowing to escape from the remedies. Comprehensive knowledge of viruses is essential for the development of targeted therapeutic and vaccination treatments. Animal models mimicking human biology like non-human primates, rats, mice, and rabbits offer competitive advantage to assess risk of viral infections, chemical toxins, nanoparticles, and microbes. However, their economic maintenance has always been an issue. Furthermore, the redundancy of experimental results due to aforementioned aspects is also in examine. Hence, exploration for the alternative animal models is crucial for risk assessments. The current review examines zebrafish traits and explores the possibilities to monitor emerging bio-contaminants. Additionally, a comprehensive picture of the bio contaminant and virus particle invasion and abatement mechanisms in zebrafish and human cells is presented. Moreover, a zebrafish model to investigate the emerging viruses such as coronaviridae and poxviridae has been suggested.

Emerging trends in the nanomedicine applications of functionalized magnetic nanoparticles as novel therapies for acute and chronic diseases.

High-quality point-of-care is critical for timely decision of disease diagnosis and healthcare management. In this regard, biosensors have revolutionized the field of rapid testing and screening, however, are confounded by several technical challenges including material cost, half-life, stability, site-specific targeting, analytes specificity, and detection sensitivity that affect the overall diagnostic potential and therapeutic profile. Despite their advances in point-of-care testing, very few classical biosensors have proven effective and commercially viable in situations of healthcare emergency including the recent COVID-19 pandemic. To overcome these challenges functionalized magnetic nanoparticles (MNPs) have emerged as key players in advancing the biomedical and healthcare sector with promising applications during the ongoing healthcare crises. This critical review focus on understanding recent developments in theranostic applications of functionalized magnetic nanoparticles (MNPs). Given the profound global economic and health burden, we discuss the therapeutic impact of functionalized MNPs in acute and chronic diseases like small RNA therapeutics, vascular diseases, neurological disorders, and cancer, as well as for COVID-19 testing. Lastly, we culminate with a futuristic perspective on the scope of this field and provide an insight into the emerging opportunities whose impact is anticipated to disrupt the healthcare industry.

Effect of Probiotics on Host-Microbial Crosstalk: A Review on Strategies to Combat Diversified Strain of Coronavirus

The scare of the ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), does not seem to fade away, while there is a constant emergence of novel deadly variants including Alpha, Beta, Gamma, Delta and Omicron. Until now, it has claimed approximately 276,436,619 infections, and the number of deaths surpluses to 5,374,744 all over the world. While saving the life has been a priority during the ongoing SARS-CoV-2 pandemic, the post-infection healing and getting back to normalcy has been undermined. Improving general health conditions and immunity with nutritional adequacy is currently of precedence for the government as well as frontline health workers to prevent and assuage infections. Exploring the role of probiotics and prebiotics in managing the after-effects of a viral outbreak could be of great significance, considering the emergence of new variants every now and then. To enhance human immunity, the recent evidence on the connection between gut microbiota and the broad spectrum of the clinical COVID-19 disease is the reason to look at the benefits of probiotics in improving health conditions. This review aims to sketch out the prospective role of probiotics and prebiotics in improving the standard of health in common people.

Structure-based drug designing and immunoinformatics approach for SARS-CoV-2.

The prevalence of respiratory illness caused by the novel SARS-CoV-2 virus associated with multiple organ failures is spreading rapidly because of its contagious human-to-human transmission and inadequate globalhealth care systems. Pharmaceutical repurposing, an effective drug development technique using existing drugs, could shorten development time and reduce costs compared to those of de novo drug discovery. We carried out virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (Mpro), and the SARS-CoV-2 receptor binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed enhanced binding affinity to all the targets. Furthermore, the postfusion conformation of the trimeric S protein RBD with ACE2 revealed conformational changes associated with PC786 drug binding. Exploiting immunoinformatics to identify T cell and B cell epitopes could guide future experimental studies with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability.

Next-Generation Bioinformatics Approaches and Resources for Coronavirus Vaccine Discovery and Development-A Perspective Review.

COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To fight this pandemic, which has caused a massive death toll around the globe, researchers are putting efforts into developing an effective vaccine against the pathogen. As genome sequencing projects for several coronavirus strains have been completed, a detailed investigation of the functions of the proteins and their 3D structures has gained increasing attention. These high throughput data are a valuable resource for accelerating the emerging field of immuno-informatics, which is primarily aimed toward the identification of potential antigenic epitopes in viral proteins that can be targeted for the development of a vaccine construct eliciting a high immune response. Bioinformatics platforms and various computational tools and databases are also essential for the identification of promising vaccine targets making the best use of genomic resources, for further experimental validation. The present review focuses on the various stages of the vaccine development process and the vaccines available for COVID-19. Additionally, recent advances in genomic platforms and publicly available bioinformatics resources in coronavirus vaccine discovery together with related immunoinformatics databases and advances in technology are discussed.

Next-generation computational tools and resources for coronavirus research: From detection to vaccine discovery.

The COVID-19 pandemic has affected 215 countries and territories around the world with 60,187,347 coronavirus cases and 17,125,719 currently infected patients confirmed as of the November 25, 2020. Currently, many countries are working on developing new vaccines and therapeutic drugs for this novel virus strain, and a few of them are in different phases of clinical trials. The advancement in high-throughput sequence technologies, along with the application of bioinformatics, offers invaluable knowledge on genomic characterization and molecular pathogenesis of coronaviruses. Recent multi-disciplinary studies using bioinformatics methods like sequence-similarity, phylogenomic, and computational structural biology have provided an in-depth understanding of the molecular and biochemical basis of infection, atomic-level recognition of the viral-host receptor interaction, functional annotation of important viral proteins, and evolutionary divergence across different strains. Additionally, various modern immunoinformatic approaches are also being used to target the most promiscuous antigenic epitopes from the SARS-CoV-2 proteome for accelerating the vaccine development process. In this review, we summarize various important computational tools and databases available for systematic sequence-structural study on coronaviruses. The features of these public resources have been comprehensively discussed, which may help experimental biologists with predictive insights useful for ongoing research efforts to find therapeutics against the infectious COVID-19 disease.

DBCOVP: A database of coronavirus virulent glycoproteins.

Since the emergence of SARS-CoV-1 (2002), novel coronaviruses have emerged periodically like the MERS- CoV (2012) and now, the SARS-CoV-2 outbreak which has posed a global threat to public health. Although, this is the third zoonotic coronavirus breakout within the last two decades, there are only a few platforms that provide information about coronavirus genomes. None of them is specific for the virulence glycoproteins and complete sequence-structural features of these virulence factors across the betacoronavirus family including SARS-CoV-2 strains are lacking. Against this backdrop, we present DBCOVP (http://covp.immt.res.in/), the first manually-curated, web-based resource to provide extensive information on the complete repertoire of structural virulent glycoproteins from coronavirus genomes belonging to betacoronavirus genera. The database provides various sequence-structural properties in which users can browse and analyze information in different ways. Furthermore, many conserved T-cell and B-cell epitopes predicted for each protein are present that may perform a significant role in eliciting the humoral and cellular immune response. The tertiary structure of the epitopes together with the docked epitope-HLA binding-complex is made available to facilitate further analysis. DBCOVP presents an easy-to-use interface with in-built tools for similarity search, cross-genome comparison, phylogenetic, and multiple sequence alignment. DBCOVP will certainly be an important resource for experimental biologists engaged in coronavirus research studies and will aid in vaccine development.

Designing an efficient multi-epitope vaccine displaying interactions with diverse HLA molecules for an efficient humoral and cellular immune response to prevent COVID-19 infection.

BACKGROUND: The novel SARS-CoV-2 coronavirus, the causative agent of the ongoing pandemic COVID-19 disease continues to infect people globally and has infected millions of humans worldwide. However, no effective vaccine against this virus exists. METHOD: Using Immunoinformatics, epitopic sequences from multiple glycoproteins that play crucial role in pathogenesis were identified. Particularly, epitopes were mapped from conserved receptor-binding domain of spike protein which have been experimentally validated in SARS-CoV-1 as a promising target for vaccine development. RESULTS: A multi-epitopic vaccine construct comprising of B-cell, CTL, HTL epitopes was developed along with fusion of adjuvant and linkers. The epitopes identified herein are reported for the first time and were predicted to be highly antigenic, stable, nonallergen, nontoxic and displayed conservation across several SARS-CoV-2 isolates from different countries. Additionally, the epitopes associated with maximum HLA alleles and population coverage analysis shows the proposed epitopes would be a relevant representative of large proportion of the world population. A reliable three-dimensional structure of the vaccine construct was developed. Consequently, docking and molecular-dynamics simulation ensured the stable interaction between vaccine and innate-immune receptor.

Effect of mutation on structure, function and dynamics of receptor binding domain of human SARS-CoV-2 with host cell receptor ACE2: a molecular dynamics simulations study.

Recent studies have pointed the role of angiotensin-converting enzyme-II (ACE2) in mediating the entry of SARS-CoV-2 to the host cell by binding to the receptor-binding domain (RBD) of viral spike protein, and successive priming by cellular proteases initiates the infection. SARS-CoV replication rate and disease severity is controlled by the binding affinity of RBD with ACE2. To understand, how mutations in the conserved residues of RBD affect the molecular interaction with ACE2, we generated five alanine mutants i.e. Y449A, N487A, Y489A, N501A and Y505A in the receptor binding motif (RBM) of the ACE2-RBD SARS-CoV-2 complex (PDB: 6M0J). Computational site directed mutagenesis induced dynamics in wild-type and mutant complexes were extensively studied through all-atoms molecular dynamics (MD) simulations of 150 ns. In silico mutational analysis revealed loss of important intermolecular hydrogen bonds and other non-bonded contacts, critical for molecular recognition of SARS-CoV-2 RBD to ACE2, which is well supported by saturation mutagenesis study of binding interface residues. MD simulations results showed that RBM motif is flexible, where mutant residues are relatively more mobile than corresponding wild-type residues. Global motion analysis through principal component studies revealed that RBD exhibits protuberant in-ward motion towards the human ACE2 binding interface which may be crucial for molecular interaction. Conclusively, the present finding are in congruence with previous experimental reports and provides detailed information on the structural basis of receptor binding by human SARS-CoV-2, which will crucial for the development of novel inhibitors or drugs to combat against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.