Missense mutations in spike protein of SARS-CoV-2 delta variant contribute to the alteration in viral structure and interaction with hACE2 receptor.

INTRODUCTION: Many of the global pandemics threaten human existence over the decades among which coronavirus disease (COVID-19) is the newest exposure circulating worldwide. The RNA encoded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is referred as the pivotal agent of this deadly disease that induces respiratory tract infection by interacting host ACE2 receptor with its spike glycoprotein. Rapidly evolving nature of this virus modified into new variants helps in perpetrating immune escape and protection against host defense mechanism. Consequently, a new isolate, delta variant originated from India is spreading perilously at a higher infection rate. METHODS: In this study, we focused to understand the conformational and functional significance of the missense mutations found in the spike glycoprotein of SARS-CoV-2 delta variant performing different computational analysis. RESULTS: From physiochemical analysis, we found that the acidic isoelectric point of the virus elevated to basic pH level due to the mutations. The targeted mutations were also found to change the interactive bonding pattern and conformational stability analyzed by the molecular dynamic's simulation. The molecular docking study also revealed that L452R and T478K mutations found in the RBD domain of delta variant spike protein contributed to alter interaction with the host ACE2 receptor. CONCLUSIONS: Overall, this study provided insightful evidence to understand the morphological and attributive impact of the mutations on SARS-CoV-2 delta variant.

Three-Dimensional Visualization of Viral Structure, Entry, and Replication Underlying the Spread of SARS-CoV-2.

The global spread of SARS-CoV-2 has proceeded at an unprecedented rate. Remarkably, characterization of the virus using modern tools in structural biology has also progressed at exceptional speed. Advances in electron-based imaging techniques, combined with decades of foundational studies on related viruses, have enabled the research community to rapidly investigate structural aspects of the novel coronavirus from the level of individual viral proteins to imaging the whole virus in a native context. Here, we provide a detailed review of the structural biology and pathobiology of SARS-CoV-2 as it relates to all facets of the viral life cycle, including cell entry, replication, and three-dimensional (3D) packaging based on insights obtained from X-ray crystallography, cryo-electron tomography, and single-particle cryo-electron microscopy. The structural comparison between SARS-CoV-2 and the related earlier viruses SARS-CoV and MERS-CoV is a common thread throughout this review. We conclude by highlighting some of the outstanding unanswered structural questions and underscore areas that are under rapid current development such as the design of effective therapeutics that block viral infection.

The Relation of the Viral Structure of SARS-CoV-2, High-Risk Condition, and Plasma Levels of IL-4, IL-10, and IL-15 in COVID-19 Patients Compared to SARS and MERS Infections.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has a high mortality rate due to widespread infection and strong immune system reaction. Interleukins (ILs) are among the main immune factors contributing to the deterioration of the immune response and the formation of cytokine storms in coronavirus 2019 (COVID-19) infections. INTRODUCTION: This review article aimed at investigating the relationship between virus structure, risk factors, and patient plasma interleukin levels in infections caused by the coronavirus family. METHODS: The keywords "interleukin," "coronavirus structure," "plasma," and "risk factors" were searched to find a relationship among different interleukins, coronavirus structures, and risk factors in ISI, PUBMED, SCOPUS, and Google Scholar databases. RESULTS: Patients with high-risk conditions with independent panels of immune system markers are more susceptible to death caused by SARS-CoV-2. IL-4, IL-10, and IL-15 are probably secreted at different levels in patients with coronavirus infections despite the similarity of inflammatory markers. SARS-CoV-2 and SARS-CoV increase the secretion of IL-4, while it remains unchanged in MERS-CoV infection. MERS-CoV infection demonstrates increased IL-10 levels. Although IL-10 levels usually increase in SARS-CoV infection, different levels are recorded in SARS-CoV-2, i.e., it increases in some patients while it decreases in others. This difference may be due to factors such as the patient's condition and the pathogenicity of SARS-CoV-2. MERS-CoV increases IL-15 secretion while its levels remain unchanged in SARS-CoV-2. The levels of IL-15 in patients with SARS-CoV have not been studied. CONCLUSION: In conclusion, the different structures of SARS-CoV-2, such as length of spike or nonstructural proteins (NSPs) and susceptibility of patients due to differences in their risk factors, may lead to differences in immune marker secretion and pathogenicity. Therefore, identifying and controlling interleukin levels can play a significant role in managing the symptoms and developing individual-specific treatments.

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.

Clinical and molecular aspects of veterinary coronaviruses.

Coronaviruses are a large group of RNA viruses that infect a wide range of animal species. The replication strategy of coronaviruses involves recombination and mutation events that lead to the possibility of cross-species transmission. The high plasticity of the viral receptor due to a continuous modification of the host species habitat may be the cause of cross-species transmission that can turn into a threat to other species including the human population. The successive emergence of highly pathogenic coronaviruses such as the Severe Acute Respiratory Syndrome (SARS) in 2003, the Middle East Respiratory Syndrome Coronavirus in 2012, and the recent SARS-CoV-2 has incentivized a number of studies on the molecular basis of the coronavirus and its pathogenesis. The high degree of interrelatedness between humans and wild and domestic animals and the modification of animal habitats by human urbanization, has favored new viral spreads. Hence, knowledge on the main clinical signs of coronavirus infection in the different hosts and the distinctive molecular characteristics of each coronavirus is essential to prevent the emergence of new coronavirus diseases. The coronavirus infections routinely studied in veterinary medicine must be properly recognized and diagnosed not only to prevent animal disease but also to promote public health.

COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies.

Coronavirus Disease 2019 named as COVID-19 imposing a huge burden on public health as well as global economies, is caused by a new strain of betacoronavirus named as SARS-CoV-2. The high transmission rate of the virus has resulted in current havoc which highlights the need for a fast and effective approach either to prevent or treat the deadly infection. Development of vaccines can be the most prominent approach to prevent the virus to cause COVID-19 and hence will play a vital role in controlling the spread of the virus and reducing mortality. The virus uses its spike proteins for entering into the host by interacting with a specific receptor called angiotensin converting enzyme-2 (ACE2) present on the surface of alveolar cells in the lungs. Researchers all over the world are targeting the spike protein for the development of potential vaccines. Here, we discuss the immunopathological basis of vaccine designing that can be approached for vaccine development against SARS-CoV-2 infection and different platforms that are being used for vaccine development. We believe this review will increase our understanding of the vaccine designing against SARS-CoV-2 and subsequently contribute to the control of SARS-CoV-2 infections. Also, it gives an insight into the current status of vaccine development and associated outcomes reported at different phases of trial.

Superimposition of Viral Protein Structures: A Means to Decipher the Phylogenies of Viruses.

Superimposition of protein structures is key in unravelling structural homology across proteins whose sequence similarity is lost. Structural comparison provides insights into protein function and evolution. Here, we review some of the original findings and thoughts that have led to the current established structure-based phylogeny of viruses: starting from the original observation that the major capsid proteins of plant and animal viruses possess similar folds, to the idea that each virus has an innate "self". This latter idea fueled the conceptualization of the PRD1-adenovirus lineage whose members possess a major capsid protein (innate "self") with a double jelly roll fold. Based on this approach, long-range viral evolutionary relationships can be detected allowing the virosphere to be classified in four structure-based lineages. However, this process is not without its challenges or limitations. As an example of these hurdles, we finally touch on the difficulty of establishing structural "self" traits for enveloped viruses showcasing the coronaviruses but also the power of structure-based analysis in the understanding of emerging viruses.

How the COVID-19 Overcomes the Battle? An Approach to Virus Structure.

Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.