Trends in electroanalytical assays for COVID-19 diagnosis

The use of electrochemical biosensors is highlighted for SARS-CoV-2 detection and COVID-19 diagnosis. In a brief description of virus structure, fundamental features of proteins and nucleic acid are approached for a comprehensive strategy over biosensor designs. Relevant works are described and related to specific structural proteins used as viral biomarkers. Furthermore, the challenges and perspectives are pointed to the evolution of electroanalysis and the establishment of methods comparable to the gold standard, RT-PCR. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023. All rights reserved.

Current Trend of Virology in the Post COVID-19 Era with Related Topic-Based Tweet Analysis

In light of current trends in virology, we performed social media analysis of 13 main topics in the area of virology and ranked these topics with metrics such as users, posts, engagement, and influence. These metrics were monitored against the 13 keywords on Twitter for the same period (i.e., from 27 November to 6 December 2021) for benchmarking purposes. The 13 main topics were "virological Science", " preventive vaccines", "therapeutic vaccines", "viral pathogenesis", "viral immunology", "antiviral strategies", "virus structure", "virus expression", "viral resistance", "emerging viruses", "interspecies transmission", "viruses and cancer" and " viral diseases". "viral diseases" recorded the highest number of users (i.e., 905 users) and the highest number of post (i.e., about 1K posts). The second-highest number of posts were monitored to be on "therapeutic vaccines" with 729 posts from 691 users. In terms of engagement, "viral diseases" (3.4 K) were found to be on the top followed by "viruses and cancer" (3.1K). Lastly, in terms of influence, "viral diseases" recorded 9.0 million influences followed by 6.6 million influences on "emerging viruses". In summary, "viral diseases" was found to be the most engaging and influential topic highest with the highest number of posts from most of the tweet users. In relation to trending hashtags in virology, #COVID19 recorded the highest number of hashtags, followed by # omicron, #sarscov2, #publichealth, #omicronvarient, #wuhan, #originofcovid, #fauci and #epidemiology. Word clouds showing the main area of discussion were also generated for these 13 main topics.

Status of COVID-19 Pandemic Before the Administration of Vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. Lack of a voice on how to handle the pandemic impacted the management of the disease globally. Publication of the importance of masks and social distancing in preprint servers reduced the spread of the disease and deaths associated with it. Very few countries have invested in science and research and development and that has impacted the development of therapies for the pandemic. Though vaccination against COVID-19 started in December 2020, slower rate of immunizations has resulted in rapid spread of the mutant strains of SARS-CoV-2. Lack of transparency and accountability coupled with anergic leadership was responsible for the high incidence of disease and death associated with the COVID-19 pandemic.

Comparative structural analyses of selected spike protein-RBD mutations in SARS-CoV-2 lineages.

The severity of COVID-19 has been observed throughout the world as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally claimed more than 2 million lives and left a devastating impact worldwide. Recently several virulent mutant strains of this virus, such as the B.1.1.7, B.1.351, and P1 lineages, have emerged with initial predominance in UK, South Africa, and Brazil. Another extremely pathogenic B.1.617 lineage and its sub-lineages, first detected in India, are now affecting some countries at notably stronger spread-rates. The present paper computationally examines the time-based structures of B.1.1.7, B.1.351, and P1 lineages with selected spike protein mutations. The mutations in the more recently found B.1.617 lineage and its sub-lineages are explored, and the implications for multiple point mutations of the spike protein's receptor-binding domain (RBD) are described. The selected S1 mutations within the highly contagious B.1.617.2 sub-lineage, also known as the delta variant, are examined as well.

RCSB Protein Data Bank resources for structure-facilitated design of mRNA vaccines for existing and emerging viral pathogens.

Structural biologists provide direct insights into the molecular bases of human health and disease. The open-access Protein Data Bank (PDB) stores and delivers three-dimensional (3D) biostructure data that facilitate discovery and development of therapeutic agents and diagnostic tools. We are in the midst of a revolution in vaccinology. Non-infectious mRNA vaccines have been proven during the coronavirus disease 2019 (COVID-19) pandemic. This new technology underpins nimble discovery and clinical development platforms that use knowledge of 3D viral protein structures for societal benefit. The RCSB PDB supports vaccine designers through expert biocuration and rigorous validation of 3D structures; open-access dissemination of structure information; and search, visualization, and analysis tools for structure-guided design efforts. This resource article examines the structural biology underpinning the success of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccines and enumerates some of the many protein structures in the PDB archive that could guide design of new countermeasures against existing and emerging viral pathogens.

Distant residues modulate conformational opening in SARS-CoV-2 spike protein.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the attachment of the receptor-binding domain (RBD) of its spike proteins to the ACE2 receptors on the peripheral membrane of host cells. Binding is initiated by a down-to-up conformational change in the spike protein, the change that presents the RBD to the receptor. To date, computational and experimental studies that search for therapeutics have concentrated, for good reason, on the RBD. However, the RBD region is highly prone to mutations, and is therefore a hotspot for drug resistance. In contrast, we here focus on the correlations between the RBD and residues distant to it in the spike protein. This allows for a deeper understanding of the underlying molecular recognition events and prediction of the highest-effect key mutations in distant, allosteric sites, with implications for therapeutics. Also, these sites can appear in emerging mutants with possibly higher transmissibility and virulence, and preidentifying them can give clues for designing pan-coronavirus vaccines against future outbreaks. Our model, based on time-lagged independent component analysis (tICA) and protein graph connectivity network, is able to identify multiple residues that exhibit long-distance coupling with the RBD opening. Residues involved in the most ubiquitous D614G mutation and the A570D mutation of the highly contagious UK SARS-CoV-2 variant are predicted ab initio from our model. Conversely, broad-spectrum therapeutics like drugs and monoclonal antibodies can target these key distant-but-conserved regions of the spike protein.

The antigenic anatomy of SARS-CoV-2 receptor binding domain.

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 µg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

A multiscale model of virus pandemic: Heterogeneous interactive entities in a globally connected world.

This paper is devoted to the multidisciplinary modelling of a pandemic initiated by an aggressive virus, specifically the so-called SARS-CoV-2 Severe Acute Respiratory Syndrome, corona virus n.2. The study is developed within a multiscale framework accounting for the interaction of different spatial scales, from the small scale of the virus itself and cells, to the large scale of individuals and further up to the collective behaviour of populations. An interdisciplinary vision is developed thanks to the contributions of epidemiologists, immunologists and economists as well as those of mathematical modellers. The first part of the contents is devoted to understanding the complex features of the system and to the design of a modelling rationale. The modelling approach is treated in the second part of the paper by showing both how the virus propagates into infected individuals, successfully and not successfully recovered, and also the spatial patterns, which are subsequently studied by kinetic and lattice models. The third part reports the contribution of research in the fields of virology, epidemiology, immune competition, and economy focussed also on social behaviours. Finally, a critical analysis is proposed looking ahead to research perspectives.

Molecular Architecture of the SARS-CoV-2 Virus.

SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen.