scholarly journals Evaluation of SARS-CoV-2 Spike S1 Protein Response on PI3K-Mediated IL-8 Release

2021 ◽  
Vol 9 (2) ◽  
pp. 30
Author(s):  
Christina Borchers ◽  
Anita Thyagarajan ◽  
Christine M. Rapp ◽  
Jeffrey B. Travers ◽  
Ravi P. Sahu
Keyword(s):  
Cellular Responses ◽  
Mechanisms Of Action ◽  
Spike Protein ◽  
Pi3k Signaling ◽  
Therapeutic Approaches ◽  
Structural Configuration ◽  
Cellular Models ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Protein Response

A novel coronavirus related to a condition known as a severe acute respiratory syndrome (SARS) was termed as SARS Coronavirus-19 (SARS-CoV-2 or COVID-19), which has caused an unprecedented global pandemic. Extensive efforts have been dedicated worldwide towards determining the mechanisms of COVID-19 associated pathogenesis with the goals of devising potential therapeutic approaches to mitigate or overcome comorbidities and mortalities. While the mode of SARS-CoV-2 infection, its structural configuration, and mechanisms of action, including the critical roles of the Spike protein have been substantially explored, elucidation of signaling pathways regulating its cellular responses is yet to be fully determined. Notably, phosphoinositide 3-kinases (PI3K) and its downstream pathway have been exploited among potential therapeutic targets for SARS-CoV-2, and its activation modulates the release of cytokines such as IL-8. To that end, the current studies were sought to determine the response of the SARS-CoV-2 Spike S1 protein on PI3K-mediated IL-8 release using relevant and widely used cellular models. Overall, these studies indicate that PI3K signaling does not directly mediate Spike S1 protein-induced IL-8 release in these cellular models.

scholarly journals Food Containing Bioactive Flavonoids and Other Phenolic or Sulfur Phytochemicals With Antiviral Effect: Can We Design a Promising Diet Against COVID-19?

2021 ◽  
Vol 8 ◽  
Author(s):  
Martina Ghidoli ◽  
Federico Colombo ◽  
Stefano Sangiorgio ◽  
Michela Landoni ◽  
Luca Giupponi ◽  
...  
Keyword(s):  
Rational Design ◽  
Complementary Therapy ◽  
Antiviral Effect ◽  
The Novel ◽  
Therapeutic Approaches ◽  
Degree Of Protection ◽  
Global Pandemic ◽  
Cultivated Plant ◽  
Novel Coronavirus ◽  
Inflammatory Action

Since in late 2019, when the coronavirus 2 (SARS-CoV-2) pathogen of coronavirus disease 2019 (COVID-19) started to spread all over the world, causing the awful global pandemic we are still experiencing, an impressive number of biologists, infectious disease scientists, virologists, pharmacologists, molecular biologists, immunologists, and other researchers working in laboratories of all the advanced countries focused their research on the setting up of biotechnological tools, namely vaccines and monoclonal antibodies, as well as of rational design of drugs for therapeutic approaches. While vaccines have been quickly obtained, no satisfactory anti-Covid-19 preventive, or therapeutic approach has so far been discovered and approved. However, among the possible ways to achieve the goal of COVID-19 prevention or mitigation, there is one route, i.e., the diet, which until now has had little consideration. In fact, in the edible parts of plants supplying our food, there are a fair number of secondary metabolites mainly belonging to the large class of the flavonoids, endowed with antiviral or other health beneficial activities such as immunostimulating or anti-inflammatory action that could play a role in contributing to some extent to prevent or alleviate the viral infection and/or counteract the development of SARS induced by the novel coronavirus. In this review, a number of bioactive phytochemicals, in particular flavonoids, proven to be capable of providing some degree of protection against COVID-19, are browsed, illustrating their beneficial properties and mechanisms of action as well as their distribution in cultivated plant species which supply food for the human diet. Furthermore, room is also given to information regarding the amount in food, the resistance to cooking processes and, as a very important feature, the degree of bioavailability of these compounds. Concluding, remarks and perspectives for future studies aimed at increasing and improving knowledge and the possibility of using this natural complementary therapy to counteract COVID-19 and other viral pathologies are discussed.

scholarly journals High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity

2020 ◽  
Author(s):  
Jinghua Lu ◽  
Peter D. Sun
Keyword(s):  
Spike Protein ◽  
Affinity Binding ◽  
Ang Ii ◽  
High Affinity Binding ◽  
Angiotensin Converting Enzyme 2 ◽  
High Affinity ◽  
Global Pandemic ◽  
Biological Substrates ◽  
Novel Coronavirus ◽  
Entry Receptor

AbstractA novel coronavirus (SARS-CoV-2) has emerged to a global pandemic and caused significant damages to public health. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides Ang II to control vasodilatation and permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we wonder how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ~3-10 fold when fluorogenic caspase-1 substrate and Bradykinin-analog peptides were used to characterize ACE2 activity. In addition, the enhancement was mediated by ACE2 binding of RBD domain of SARS-CoV-2 spike. These results highlighted the altered activity of ACE2 during SARS-CoV-2 infection and would shed new lights on the pathogenesis of COVID-19 and its complications for better treatments.

scholarly journals Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19

2020 ◽  
Vol 9 (4) ◽  
pp. 1131 ◽  
Author(s):  
Jiansheng Huang ◽  
Wenliang Song ◽  
Hui Huang ◽  
Quancai Sun
Keyword(s):  
Rna Polymerase ◽  
The United States ◽  
Spike Protein ◽  
Therapeutic Approaches ◽  
Rna Dependent Rna Polymerase ◽  
S Protein ◽  
Functional Relationships ◽  
Human Lung Cells ◽  
Novel Coronavirus

An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. In the United States, one case of COVID-19 was successfully treated with compassionate use of remdesivir in January of 2020. In addition, a clinically proven protease inhibitor, camostat mesylate, has been demonstrated to inhibit Calu-3 infection with SARS-CoV-2 and prevent SARS-2-spike protein (S protein)-mediated entry into primary human lung cells. Here, we systemically discuss the pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase and S protein for treatment of SARS-CoV-2 infection. This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.

scholarly journals SARS-CoV-2 Assays To Detect Functional Antibody Responses That Block ACE2 Recognition in Vaccinated Animals and Infected Patients

2020 ◽  
Vol 58 (11) ◽  
Author(s):  
Susanne N. Walker ◽  
Neethu Chokkalingam ◽  
Emma L. Reuschel ◽  
Mansi Purwar ◽  
Ziyang Xu ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
The United States ◽  
Spike Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Single Experiment ◽  
Severe Respiratory Distress ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Significant Mortality

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and nonhuman primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor blocking of sera from SARS-CoV-2-infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and assess the efficacy of vaccines.

scholarly journals Virtual Screening and In Silico Interactions Studies for Potential Antivirals and Diagnostics against the Spike protein from the Novel Coronavirus SARS-Cov-2

2021 ◽  
Vol 1192 (1) ◽  
pp. 012025
Author(s):  
F I Che Abd Aziz ◽  
F A Ahmad Fuad ◽  
S Tanbin
Keyword(s):  
Monoclonal Antibodies ◽  
Binding Energy ◽  
Virtual Screening ◽  
Spike Protein ◽  
Protein Protein Interaction ◽  
Entry Pathway ◽  
Therapeutic Drugs ◽  
Global Pandemic ◽  
Potential Spike ◽  
Novel Coronavirus

Abstract COVID-19 is a newly-emerged respiratory disease that is caused by the SARS-CoV-2, the seventh known Coronaviruses strain that has struck a global pandemic. The sharp increase in the number of positive cases worldwide necessitates highly-sensitive diagnostics kits and effective antiviral drugs to be developed for the populations. One of the antigens that is targeted for antibody neutralisation is the coronavirus Spike protein that consists of the S1 and S2 subunits, which mediated the entry pathway into the host’s cell. Thus, the Spike protein has been suggested as a potential target for Covid-19 diagnostics and drug design. This study aims to evaluate the interactions between the SARS-CoV-2 Spike protein and the known monoclonal antibodies from Coronaviruses and to screen for potential Spike protein inhibitors. Virtual screening was conducted based on two compounds, N‐acetyl‐D‐glucosamine (NAG) and Hesperetin, which is a small molecule that binds to the SARS-CoV-2 Spike protein structure and a natural compound that has prophylactic agents against SARS-CoV-2 infection as it binds to Spike protein, respectively. Protein-protein interaction studies were conducted by using the STRING webserver, prior to performing rigid docking using SWISSDOCK and visualised using USCF Chimera. Meanwhile, ligand-based screening was conducted through Ultrafast Shape Recognition Virtual Screening Database (USR-VS), and structure-based screening was performed via AutoDock4 software. The toxicity of the compounds was predicted using ProTox-II database. Possible interactions have been observed between the known monoclonal antibodies with the SARS-CoV-2 Spike protein, where M396 monoclonal antibody has shown the strongest interaction with a binding energy of -8.50 kcal/mol. Meanwhile, virtual screening has yielded several compounds that indicate the possibility to inhibit the SARS-CoV-2 Spike protein, where Tamarixetin has shown the strongest binding energy of -7.93 kcal/mol. These findings have potentials to be further evaluated in the future for the development of improved diagnostic kits and potential therapeutic drugs that specifically target the Spike protein of SARS-CoV-2.

scholarly journals Potential Plants for Treatment and Management of COVID-19 in Nigeria

2020 ◽  
pp. 69-80
Author(s):  
Ikpa Chiyere B. C. ◽  
Maduka Tochukwu O. D. ◽  
Christian Ebere Enyoh ◽  
Ikezu Uju J. M.
Keyword(s):  
Death Rate ◽  
Allium Sativum ◽  
Curcuma Longa ◽  
Zingiber Officinale ◽  
Viral Proteins ◽  
Natural Compounds ◽  
Therapeutic Approaches ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Potential Use

The recent outburst of novel Coronavirus disease (COVID-19), now a global pandemic highlights an urgent need for therapeutics targeting ‘severe acute respiratory syndrome’ (SARS-CoV-2). In Nigeria, infection cases are on daily rise with death rate of ~3 %. Therefore, slowing the spread of the virus will significantly reduce the strain on the healthcare system and governments. Here, we presented local medicinal plants cultivated in Nigeria as possible therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways. The study focused on some plants containing bioactive compounds that showed promising results against previous coronaviruses. Potential plants identified include Zingiber officinale, Allium cepa, Allium sativum, echinacea, euphorbia hirta, Garcenea kola, Curcuma longa, Aleo vera and olea europaea. Although inhibition of viral replication is seen as the possible mechanism for antiviral activity of most of the natural compounds, recent research has shown that some natural compounds can interact with major viral proteins associated with virulence. Thereby, showing they could be a valuable tool for possible inhibition, management and treatment of SARS-CoV-2. However, further research is required to investigate and validate their potential use as anti-SARS-CoV-2.

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

Novel Coronavirus SARS-CoV-2 (COVID-19) and Pregnancy: A hypothetical view

2020 ◽  
Vol 20 ◽  
Author(s):  
Ahmed RG
Keyword(s):  
Immune System ◽  
Cellular Therapy ◽  
Early Stage ◽  
Control Strategies ◽  
Vital Role ◽  
Healthy Life ◽  
Global Pandemic ◽  
Maternal Immune System ◽  
Perinatal Management ◽  
Novel Coronavirus

Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

scholarly journals Circular RNAs: Potential Applications as Therapeutic Targets and Biomarkers in Breast Cancer

2021 ◽  
Vol 7 (1) ◽  
pp. 2
Author(s):  
Debina Sarkar ◽  
Sarah D. Diermeier
Keyword(s):  
Breast Cancer ◽  
Translational Regulation ◽  
Closed Loop ◽  
Mechanisms Of Action ◽  
Circular Rnas ◽  
Therapeutic Approaches ◽  
Mirna Sponge ◽  
Bodily Fluids ◽  
Potential Applications ◽  
Non Coding Rnas

Circular RNAs (circRNAs) are a class of non-coding RNAs that form a covalently closed loop. A number of functions and mechanisms of action for circRNAs have been reported, including as miRNA sponge, exerting transcriptional and translational regulation, interacting with proteins, and coding for peptides. CircRNA dysregulation has also been implicated in many cancers, such as breast cancer. Their relatively high stability and presence in bodily fluids makes cancer-associated circRNAs promising candidates as a new biomarker. In this review, we summarize the research undertaken on circRNAs associated with breast cancer, discuss circRNAs as biomarkers, and present circRNA-based therapeutic approaches.

scholarly journals Progression and Trends in Virus from Influenza A to COVID-19: An Overview of Recent Studies

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1145
Author(s):  
Hakimeh Baghaei Daemi ◽  
Muhammad Fakhar-e-Alam Kulyar ◽  
Xinlin He ◽  
Chengfei Li ◽  
Morteza Karimpour ◽  
...  
Keyword(s):  
Influenza A ◽  
H1n1 Virus ◽  
World Health ◽  
H1n1 Pandemic ◽  
Global Pandemic ◽  
First Case ◽  
Influenza A H1n1 ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

Influenza is a highly known contagious viral infection that has been responsible for the death of many people in history with pandemics. These pandemics have been occurring every 10 to 30 years in the last century. The most recent global pandemic prior to COVID-19 was the 2009 influenza A (H1N1) pandemic. A decade ago, the H1N1 virus caused 12,500 deaths in just 19 months globally. Now, again, the world has been challenged with another pandemic. Since December 2019, the first case of a novel coronavirus (COVID-19) infection was detected in Wuhan. This infection has risen rapidly throughout the world; even the World Health Organization (WHO) announced COVID-19 as a worldwide emergency to ensure human health and public safety. This review article aims to discuss important issues relating to COVID-19, including clinical, epidemiological, and pathological features of COVID-19 and recent progress in diagnosis and treatment approaches for the COVID-19 infection. We also highlight key similarities and differences between COVID-19 and influenza A to ensure the theoretical and practical details of COVID-19.

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