scholarly journals Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations

2020 ◽  
Vol 13 (10) ◽  
pp. 277 ◽  
Author(s):  
Anastasiia I. Petushkova ◽  
Andrey A. Zamyatnin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Genome ◽  
Drug Targets ◽  
Structural Features ◽  
The Third ◽  
Frequent Mutations ◽  
Near Future ◽  
Viral Reproduction

Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future.

scholarly journals Comparison of Immune Response between SARS, MERS, and COVID-19 Infection, Perspective on Vaccine Design and Development

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hossein Ansariniya ◽  
Seyed Mohammad Seifati ◽  
Erfan Zaker ◽  
Fateme Zare
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Middle East Respiratory Syndrome ◽  
Immune Stimulation ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
New Vaccines

Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) infections are the three epidemiological diseases caused by the Coronaviridae family. Perceiving the immune responses in these infections and the escape of viruses could help us design drugs and vaccines for confronting these infections. This review investigates the innate and adaptive immune responses reported in the infections of the three coronaviruses SARS, MERS, and COVID-19. Moreover, the present study can trigger researchers to design and develop new vaccines and drugs based on immune system responses. In conclusion, due to the need for an effective and efficient immune stimulation against coronavirus, a combination of several strategies seems necessary for developing the vaccine.

scholarly journals Immune Response to SARS-CoV-2 Infection

2020 ◽  
Vol 03 (10) ◽  
Author(s):  
Dr. Ahmed Al-Shukaili ◽  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Global Health ◽  
Immune Cells ◽  
Current Knowledge ◽  
Adaptive Immune ◽  
Proinflammatory Mediators ◽  
Adaptive Immune Cells ◽  
New Type

In December 2019 a new type of coronaviruses appeared in China and named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the disease associated with this virus is called Coronavirus Disease 2019 or COVID-19. Currently, COVID19 is the main global health threat. In this review, we focus in the current knowledge of immune response to SARS-CoV-2. Dysregulation of immune system, such as elevation levels of proinflammatory mediators and their roles in disease progression and pathogenesis as well as imbalance between innate and adaptive immune cells, are discussed in this review.

scholarly journals Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruirong Chen ◽  
Zhien Lan ◽  
Jujian Ye ◽  
Limin Pang ◽  
Yi Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Distress Syndrome ◽  
The Novel ◽  
Cytokine Storm ◽  
Major Threat ◽  
Primary Determinant ◽  
Multi Organ Dysfunction Syndrome

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.

scholarly journals Choice of Food: A Preventive Measure during Covid-19 Outbreak

2020 ◽  
Vol 2 (1) ◽  
pp. 85-89
Author(s):  
Archana Bhatta
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Research Evidence ◽  
Preventive Measures ◽  
Preventive Measure ◽  
Personal Hygiene ◽  
Immune Functions ◽  
Key Factor ◽  
Research Findings

As the Covid-19 pandemic has affected communities around the globe, people are facing the fear of being infected by it. It is believed that Coronavirus disease 2019 is directly associated to an individual’s immune response, with no documented research evidence found yet. But, Covid-19 is genetically similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), therefore the same immune response is expected for Covid-191. It has also been found that individuals having weaker immune functions are more suspected to infect and have a high fatality rate2. Preventive measures such as good personal hygiene, wearing a mask, avoiding crowded places and sick individuals, practicing quarantine, and proper choice of food can help an individual to be safe from the risk of current COVID-19 infection. Research findings state that nutrition influences immune strength thereby protecting our body from the attack of pathogens3. Increasing intake of a nutritious diet can help to enhance the immune system and makes an individual less susceptible to diseases, which is also considered as a key factor for the prevention of viral infection like COVID-19. Therefore, the incorporation of foods rich in nutrients that boosts our immunity is one of the possible essential preventive measures to fight with this global crisis.

scholarly journals SARS-CoV-2 and Autoimmune Cytopenia

Hemato ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 463-476
Author(s):  
Ryann Quinn ◽  
Irina Murakhovskaya
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Thrombocytopenic Purpura ◽  
Clinical Course ◽  
Clinical Manifestations ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Autoimmune Cytopenias ◽  
Autoimmune Cytopenia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a variety of clinical manifestations related to viral tissue damage, as well as a virally induced immune response. Hyperstimulation of the immune system can serve as a trigger for autoimmunity. Several immune-mediated manifestations have been described in the course of SARS-CoV-2 infection. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are the most common hematologic autoimmune disorders seen in the course of SARS-CoV-2 infection. Vaccine-induced thrombocytopenia is a unique autoimmune hematologic cytopenia associated with SARS-CoV-2 vaccination. This paper will review the current literature on the association of SARS-CoV-2 infection and vaccination with autoimmune cytopenias and the clinical course of autoimmune cytopenias in patients with COVID-19.

Perspective of molecular immune response of SARS-COV-2 infection

2020 ◽  
Vol 9 (1) ◽  
pp. 58-66
Author(s):  
Martina Kurnia Rohmah ◽  
Arif Rahman Nurdianto
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Organ Damage ◽  
Research Progress ◽  
Respiration Disorders ◽  
Immune Intervention ◽  
The Third ◽  
The Past ◽  
Pro Inflammatory Cytokines

COVID-19 is a type of Pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). When COVID-19 arise in Wuhan China and rapidly spread throughout to the World, we need to learn how pathogenesis and immune responses occur in the bodies in more detail. COVID-19 is the third Severe Respiratory Disease outbreak caused by the Coronavirus in the past two decades after Severe Acute Respiratory Syndrome (SARS) in the 2002 and Middle East Respiratory Syndrome (MERS) in 2012. The Articles from PUBMED and Research Gate were searched for studies on the immune response of COVID-19 infection by SARS-CoV-2. SARS-CoV-2 increases the number of neutrophils, suppresses IFN, increases the activity of Th1/Th17, B cells, CD8+ and CD4+, and causes cytokine storms especially pro-inflammatory cytokines which can increase respiration disorders and multi-organ damage. This review tries to explain about pathogenesis and immune responses of COVID-19 to provide a reference in designing the appropriate immune intervention for treatment and therapeutic such as drug or vaccine based on the recent research progress SARS-CoV-2 and previous studies about SARS CoV and MERS CoV.

scholarly journals Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Farooq Rashid ◽  
Muhammad Suleman ◽  
Abdullah Shah ◽  
Emmanuel Enoch Dzakah ◽  
Shuyi Chen ◽  
...  
Keyword(s):  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Evasion ◽  
Structural Features ◽  
Binding Energies ◽  
Host Immune System ◽  
Structural Protein ◽  
Dynamic Features ◽  
Human Immune System ◽  
Design Structure

Mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made this virus more infectious. Previous studies have confirmed that non-structural protein 13 (NSP13) plays an important role in immune evasion by physically interacting with TANK binding kinase 1 (TBK1) to inhibit IFNβ production. Mutations have been reported in NSP13; hence, in the current study, biophysical and structural modeling methodologies were adapted to dissect the influence of major mutations in NSP13, i.e., P77L, Q88H, D260Y, E341D, and M429I, on its binding to the TBK1 and to escape the human immune system. The results revealed that these mutations significantly affected the binding of NSP13 and TBK1 by altering the hydrogen bonding network and dynamic structural features. The stability, flexibility, and compactness of these mutants displayed different dynamic features, which are the basis for immune evasion. Moreover, the binding was further validated using the MM/GBSA approach, revealing that these mutations have higher binding energies than the wild-type (WT) NSP13 protein. These findings thus justify the basis of stronger interactions and evasion for these NSP13 mutants. In conclusion, the current findings explored the key features of the NSP13 WT and its mutant complexes, which can be used to design structure-based inhibitors against the SARS-CoV-2 new variants to rescue the host immune system.

scholarly journals Lehetőségek és buktatók a SARS-CoV-2-antigén és az ellene termelt antitestek kimutatásában

2021 ◽  
Vol 162 (15) ◽  
pp. 563-570
Author(s):  
Melinda Medgyaszai ◽  
Zalán Péterfi ◽  
Anna Valkó
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Infectious Diseases ◽  
Human Body ◽  
Scientific Knowledge ◽  
Diagnostic Tests ◽  
Serological Testing ◽  
Medical Opinion ◽  
Over Time

Összefoglaló. A koronavírus-betegség 2019 (COVID–19)-pandémia komoly kihívás elé állította nemcsak a mikrobiológiai laboratóriumokat, hanem az eredmények interpretálásában a klinikumban dolgozó kollégákat is. Az orvostudomány specializált világában az immunológiai és a fertőző betegségekkel kapcsolatos ismeretek az antimikrobás terápiás megoldások sikeressége, valamint a széles körű vakcináció miatt az idők folyamán számos szakterületen háttérbe szorultak, felfrissítésük sürgető és elengedhetetlen része a pandémiával való megküzdésnek. A diagnosztikai vizsgálatok fontos eszközei a járvány megfékezésének, illetve a betegek ellátásának, azonban a vírus és az emberi szervezet interakciójának megértése elengedhetetlenül szükséges a korrekt epidemiológiai és gyógyászati véleményalkotáshoz. Jelen cikkünk az orvosi gyakorlat számára foglalja össze a súlyos akut légzőszervi szindrómát okozó koronavírus-2 (SARS-CoV-2) kimutatására, valamint az immunrendszer specifikus immunválaszának szerológiai vizsgálatára irányuló, gyakorlatban használatos módszereket, azok helyét, szerepét és értékelésük szempontjait a tudomány jelen állása szerint. Orv Hetil. 2021; 162(15): 563–570. Summary. The coronavirus disease 2019 (COVID-19) pandemic posed a serious challenge not only for microbiology laboratories, but also for the clinicians in interpretation of the results. In the specialized world of medicine, knowledge of immunological and infectious diseases has been relegated to the background in many disciplines over time due to the success of antimicrobial therapies and widespread vaccination, so updating them is an urgent and essential part of the fight against the pandemic. Diagnostic tests are important tools for controlling the epidemic and caring for patients, but understanding the interaction between the virus and the human body is essential to form a correct epidemiological and medical opinion. This paper summarizes the medical methods for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the serological testing of the specific immune response of the immune system, their place, role and criteria of their evaluation according to current scientific knowledge. Orv Hetil. 2021; 162(15): 563–570.

scholarly journals Review of Pathologies on MOR 693: An Allosaurus from the Late Jurassic of Wyoming and Implications for Understanding Allosaur Immune Systems

2019 ◽  
Author(s):  
Jack Wilkin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Soft Tissue ◽  
Late Jurassic ◽  
Tissue Preservation ◽  
Immune Systems ◽  
Soft Tissue Preservation ◽  
The Third ◽  
Bone Infections ◽  
The Right

Palaeopathology is important as it provides remarkable insights into the lifestyles of dinosaurs and other prehistoric animals. The Late Jurassic Allosaurus known as Big Al (MOR 693) from Big Horn County, Wyoming preserves at least 19 injuries. About 2% of all bones showed abnormalities, including osteomyelitis on the right foot, on the first phalanx of the third toe, which may have contributed to the animal's death. There would likely have been many more pathologies that did not make it into the paleontological record due do the lack of soft-tissue preservation. Analysis of MOR 693’s immune response to bone infections and comparing it to other theropods, we can confidently say that dinosaurs possessed an immune system that isolated and localized infections like extant Aves.

scholarly journals PARTICULAR QUALITIES OF THE PROTEOLYTIC SYSTEM IN PATIENTS WITH TUBERCULOSIS DEPENDING ON THE SENSITIVITY OF THE PATHOGEN

2021 ◽  
Vol 74 (1) ◽  
pp. 94-97
Author(s):  
Igor D. Duzhyi ◽  
Halyna P. Oleshchenko ◽  
Ivan A. Hnatenko ◽  
Stanislav O. Holubnychyi
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Pleural Effusion ◽  
Pulmonary Tuberculosis ◽  
Neutrophil Elastase ◽  
Proteolytic System ◽  
The Third ◽  
Pleural Tuberculosis ◽  
Dual Localization ◽  
Tuberculous Pleurisy

The aim: Studying the features of the proteolytic system in patients with tuberculosis depending on the sensitivity of the pathogen. Materials and methods: In the course of the research we studied the level of elastase in the blood of 111 patients. The first group consisted of 66 (59.5%) people with pulmonary tuberculosis (39 were sensitive to antibacterial drugs, 27 were resistant). The second group included 13 (11.7%) patients with tuberculous pleurisy. The third group consisted of 32 (28.8%) patients with dual localization of the process (pulmonary tuberculosis and pleural tuberculosis). Results: The level of neutrophil elastase in patients with tuberculous pleurisy (253.2 nmol / min • ml) was 2.2 times higher than in patients with sensitive pulmonary tuberculosis (110.1 nmol / min • ml) and higher than in patients with resistant pulmonary tuberculosis 3.0 times. In combined pulmonary and pleural tuberculosis (third group) the level of elastase was 1.6 times higher than in pulmonary tuberculosis (176.9 nmol / min • ml)) (p <0.01), but lower than in pleurisy in 1, 4 times. In sensitive combined tuberculosis (lungs and pleura) the level of NE was 1.5 times higher than in patients of subgroup 1a (p <0.01) and 1.4 times lower than in patients with tuberculous pleurisy (p <0.01 ). Conclusions: The highest level of elastase in tuberculous pleurisy can be explained by its increased production, contributes to increased “permeability” of the pleural sheets and the accumulation of pleural effusion. In resistant forms of tuberculosis, the immune response in the form of the activity of the proteolytic system, which is lower than in sensitive forms, can be explained by the exhaustion of the immune system under the influence of aggressive tuberculosis. The above can be associated with both the weakening of the patient’s body and the aggressiveness of the pathogen.

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