scholarly journals Targeting the sAC-Dependent cAMP Pool to Prevent SARS-Cov-2 Infection

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1962
Author(s):  
Muhammad Aslam ◽  
Yury Ladilov
Keyword(s):  
Endocytic Pathway ◽  
Host Cells ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Late Endosomes ◽  
Proven Efficacy ◽  
Potential Impact ◽  
Potential Strategy ◽  
Novel Coronavirus ◽  
High Level

An outbreak of the novel coronavirus (CoV) SARS-CoV-2, the causative agent of COVID-19 respiratory disease, infected millions of people since the end of 2019, led to high-level morbidity and mortality and caused worldwide social and economic disruption. There are currently no antiviral drugs available with proven efficacy or vaccines for its prevention. An understanding of the underlying cellular mechanisms involved in virus replication is essential for repurposing the existing drugs and/or the discovery of new ones. Endocytosis is the important mechanism of entry of CoVs into host cells. Endosomal maturation followed by the fusion with lysosomes are crucial events in endocytosis. Late endosomes and lysosomes are characterized by their acidic pH, which is generated by a proton transporter V-ATPase and required for virus entry via endocytic pathway. The cytoplasmic cAMP pool produced by soluble adenylyl cyclase (sAC) promotes V-ATPase recruitment to endosomes/lysosomes and thus their acidification. In this review, we discuss targeting the sAC-specific cAMP pool as a potential strategy to impair the endocytic entry of the SARS-CoV-2 into the host cell. Furthermore, we consider the potential impact of sAC inhibition on CoV-induced disease via modulation of autophagy and apoptosis.

scholarly journals SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus

2020 ◽  
Author(s):  
Jungang Chen ◽  
Lu Dai ◽  
Lindsey Barrett ◽  
Steven R. Post ◽  
Zhiqiang Qin
Keyword(s):  
Intracellular Signaling ◽  
Host Cells ◽  
The Novel ◽  
Oncogenic Viruses ◽  
Fatal Disease ◽  
Intracellular Signaling Pathways ◽  
Lytic Reactivation ◽  
Increase Risk ◽  
Proven Efficacy ◽  
Novel Coronavirus

SummaryAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of Coronavirus Disease-2019 (COVID-19), a respiratory disease, has infected over 34,000,000 people since the end of 2019, killed over 1,000,000, and caused worldwide social and economic disruption. Due to the mechanisms of SARS-CoV-2 infection to host cells and its pathogenesis remain largely unclear, there are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Besides severe respiratory and systematic symptoms, several comorbidities may also increase risk of fatal disease outcome. Therefore, it is required to investigate the impacts of COVID-19 on pre-existing diseases of patients, such as cancer and other infectious diseases. In the current study, we have reported that SARS-CoV-2 encoded proteins and some anti-COVID-19 drugs currently used are able to induce lytic reactivation of Kaposi’s sarcoma-associated herpesvirus (KSHV), one of major human oncogenic viruses through manipulation of intracellular signaling pathways. Our data indicate that those KSHV+ patients especially in endemic areas exposure to COVID-19 or undergoing the treatment may have increased risks to develop virus-associated cancers, even after they have fully recovered from COVID-19.

scholarly journals SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jungang Chen ◽  
Lu Dai ◽  
Lindsey Barrett ◽  
Jennifer James ◽  
Karlie Plaisance-Bonstaff ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Host Cells ◽  
The Novel ◽  
Oncogenic Viruses ◽  
Fatal Disease ◽  
Intracellular Signaling Pathways ◽  
Lytic Reactivation ◽  
Increase Risk ◽  
Proven Efficacy ◽  
Novel Coronavirus

AbstractAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of Coronavirus Disease-2019 (COVID-19), a respiratory disease, has infected almost one hundred million people since the end of 2019, killed over two million, and caused worldwide social and economic disruption. Because the mechanisms of SARS-CoV-2 infection of host cells and its pathogenesis remain largely unclear, there are currently no antiviral drugs with proven efficacy. Besides severe respiratory and systematic symptoms, several comorbidities increase risk of fatal disease outcome. Therefore, it is required to investigate the impacts of COVID-19 on pre-existing diseases of patients, such as cancer and other infectious diseases. In the current study, we report that SARS-CoV-2 encoded proteins and some currently used anti-COVID-19 drugs are able to induce lytic reactivation of Kaposi’s sarcoma-associated herpesvirus (KSHV), one of major human oncogenic viruses, through manipulation of intracellular signaling pathways. Our data indicate that those KSHV + patients especially in endemic areas exposure to COVID-19 or undergoing the treatment may have increased risks to develop virus-associated cancers, even after they have fully recovered from COVID-19.

scholarly journals Pulmonary Cavitation – An Under-recognized Late Complication of Severe COVID-19 Lung Disease

2020 ◽  
Author(s):  
Zaid Zoumot ◽  
Maria-Fernanda Bonilla ◽  
Ali S. Wahla ◽  
Irfan Shafiq ◽  
Mateen Uzbeck ◽  
...  
Keyword(s):  
Lung Disease ◽  
Medical Records ◽  
Late Complication ◽  
Ground Glass ◽  
The Novel ◽  
Radiological Findings ◽  
Imaging Characteristics ◽  
Microbiological Parameters ◽  
Novel Coronavirus ◽  
High Level

Abstract Background: Pulmonary radiological findings of the novel coronavirus disease 2019 (COVID-19) have been well documented and range from scattered ground-glass infiltrates in milder cases to confluent ground-glass change, dense consolidation, and crazy paving in the critically ill. However, lung cavitation has not been commonly described in these patients. The objective of this study was to assess the incidence of pulmonary cavitation in patients with COVID-19 and describe its characteristics and evolution.Methods: We conducted a retrospective review of all patients admitted to our institution with COVID-19 and reviewed electronic medical records and imaging to identify patients who developed pulmonary cavitation.Results: Twelve out of 689 (1.7%) patients admitted to our institution with COVID-19 developed pulmonary cavitation, comprising 3.3% (n=12/359) of patients who developed COVID-19 pneumonia, and 11% (n=12/110) of those admitted to the intensive care unit. We describe the imaging characteristics of the cavitation and present the clinical, pharmacological, laboratory, and microbiological parameters for these patients. In this cohort six patients have died, two are recovering in hospital and four have been discharged home. Conclusion: Cavitary lung disease in patients with severe COVID-19 disease is not uncommon, and is associated with a high level of morbidity and mortality.

scholarly journals Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinsung Yang ◽  
Simon J. L. Petitjean ◽  
Melanie Koehler ◽  
Qingrong Zhang ◽  
Andra C. Dumitru ◽  
...  
Keyword(s):  
Binding Pocket ◽  
Living Cells ◽  
Host Cells ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Force Microscopy ◽  
Binding Interface ◽  
Atomic Force ◽  
Viral Glycoproteins ◽  
Novel Coronavirus

Abstract Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

scholarly journals Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guillaume Carissimo ◽  
Weili Xu ◽  
Immanuel Kwok ◽  
Mohammad Yazid Abdad ◽  
Yi-Hao Chan ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Whole Blood ◽  
Roc Analysis ◽  
Γδ T Cells ◽  
High Sensitivity ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Cell Counts ◽  
Novel Coronavirus

Abstract SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

scholarly journals Student-Designed Cross-Sectional Pandemic Knowledge Survey of 8th−12th Grade Students, Milwaukee, WI, April 2020

2021 ◽  
Vol 9 ◽  
Author(s):  
Krish Vasudev ◽  
Hersh Singh ◽  
August A. Neumann ◽  
William M Zhao ◽  
Lyle Dominic Pelayo Mondano
Keyword(s):  
The Novel ◽  
Cross Sectional ◽  
Safety Measures ◽  
Web Based ◽  
12Th Grade ◽  
Twelfth Grade ◽  
Level Of Understanding ◽  
Novel Coronavirus ◽  
High Level ◽  
Knowledge Survey

Background: The novel coronavirus and its effect on our society are unprecedented. Given the recent pandemic, numerous measures have been taken to protect our communities. We sought to understand our school community's knowledge and the measures that were taken by our school for our safety.Objective: Our objective was to describe the overall understanding and attitudes of 8–12th grade students from a single institution during the initial phase of the Wisconsin's Governor's stay-at-home order.Methods: A voluntary web-based survey was communicated to 8–12th grade students through their online school portal. Data were collected and analyzed using SurveyMonkey.Results: There was a 20.2% response rate. Answers regarding the coronavirus, spread, and response to the coronavirus pandemic showed a high level of understanding of the virus and the actions necessary to prevent its spread.Conclusion: Eight-twelfth grade students have a high level of understanding of the virus, its effects, and the safety measures implemented to protect society.

scholarly journals The methods of training of the Patrol-Guard Service officers in the midst of the novel coronavirus infection

2020 ◽  
pp. 64-72
Author(s):  
Maxim Yurevich Koynov
Keyword(s):  
Distance Learning ◽  
Blended Learning ◽  
Practical Training ◽  
The Novel ◽  
Distance Teaching ◽  
Learning Techniques ◽  
Coronavirus Infection ◽  
Level Of Training ◽  
Novel Coronavirus ◽  
High Level

The research subject is the methods of practical training of the Patrol-Guard Service officers via in-person learning and the inclusion of the distance learning techniques in the midst of the novel coronavirus infection (COVID-19). The research object is legal relations emerging in the process of formation of new educational methods in the midst of the novel coronavirus infection (COVID-19). The author analyzes the situation in the educational sphere connected with the use of various elements of in-person and distance teaching of the Patrol-Guard Service officers. The scientific novelty of the research consists in the consideration of elements of in-person and distance learning and in searching for the balance between these types of learning, and in the formation of the concept of blended learning and the analysis of its effectiveness in the current situation. The author’s contribution to the study of the topic is the analysis of the possibility to integrate blended learning and theoretical distance learning at the first stage, and practical in-person learning at the second stage into the system of block-module-based education used at the educational institutions of the Ministry of Internal Affairs of Russia. The author concludes that the use of the blended method of teaching allows achieving a high-level of training of the Patrol-Guard Service officers in the period of restrictions caused by the novel coronavirus infection (COVID-19).   

scholarly journals The Importance of Building Community Trust for Sustained Malaria Elimination Interventions During Unforeseen Major Disruptive Events Such as COVID-19: A Cambodia Case Study

2020 ◽  
Author(s):  
Mitra Feldman ◽  
Lieven Vernaeve ◽  
James Tibenderana ◽  
Leo Braack ◽  
Mark Debackere ◽  
...  
Keyword(s):  
Rural Communities ◽  
Malaria Elimination ◽  
The Novel ◽  
National Guidelines ◽  
Patients At Risk ◽  
Building Community ◽  
Novel Coronavirus ◽  
High Level ◽  
First Time

Abstract Background Impressive progress in reducing malaria trends combined with the 2018 report of no malaria related deaths for the first time, puts Cambodia well on track to reaching its malaria elimination goals. However, the novel coronavirus SARS-CoV-2 (COVID-19) pandemic presents a potential challenge to this goal. The path towards malaria elimination is dependent on sustained interventions to prevent rapid resurgence, which can quickly set back any gains achieved. Methods Mobile Malaria Workers (MMWs) need to have a strong understanding of the local geography and, most importantly, build and maintain trust among the communities they serve. To achieve this, Malaria Consortium uses a peer-to-peer approach for the MMWs and ensures the same level of trust operates between the MMWs and Malaria Consortium. Malaria Consortium’s policy during COVID-19 has been to follow national guidelines while continuing to support community-based malaria services via the MMWs / mobile malaria posts (MPs) with as minimal disruption as possible. A risk assessment was carried out by Malaria Consortium, with a mitigation plan quickly developed and implemented, to ensure MMWs were able to continue providing services without putting themselves or their patients at risk. Results Malaria Consortium ensured the MMW/ mobile MP program is built on trust, relevance to, and connection with the communities being served. An overall decline in malaria testing was reported from Health Centres and VMWs among all three provinces in March and April, not seen in previous years and possibly attributable to fear of COVID-19. However, Malaria Consortium supported MMWs have not reported any such decline in the utilization of their services and attribute this to the trust they have among the communities. Conclusion Malaria Consortium has effectively demonstrated care and solidarity with and among the MMWs and communities being served. This has ensured a high level of trust, and therefore willingness among the MMWs and communities to continue providing and utilising malaria services as usual despite the fear of COVID-19. Building trust among rural communities builds resilience and ensures uninterrupted and effective malaria elimination activities can continue even during a potential extraneous disruptive force, such as the Covid-19 pandemic.

scholarly journals Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

2020 ◽  
Author(s):  
Guillaume Carissimo ◽  
Weili Xu ◽  
Immanuel Kwok ◽  
Mohammad Yazid Abdad ◽  
Yi-Hao Chan ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Marker ◽  
Whole Blood ◽  
Γδ T Cells ◽  
High Sensitivity ◽  
Strongly Correlated ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Cell Counts ◽  
Novel Coronavirus

AbstractSARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 γδ T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

scholarly journals Controlling the cascade of corona

2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Muneeba Azmat
Keyword(s):  
Public Health ◽  
The Novel ◽  
Limited Data ◽  
Press Releases ◽  
The Public ◽  
Health Measures ◽  
First Case ◽  
Pandemic Response ◽  
Potential Impact ◽  
Novel Coronavirus

The pandemic of the 2019 novel Coronavirus has seen unprecedented exponential growth. Within three months, 192 countries have been affected, crossing more than 1 million confirmed cases and over 60 thousand deaths until the first week of April. Decision making in such a pandemic becomes difficult due to limited data on the nature of the disease and its propagation, course, prevention, and treatment. The pandemic response has varied from country to country and has resulted in a heterogeneous timeline for novel Coronavirus propagation. We compared the public health measures taken by various countries and the potential impact on the spread. We studied 6 countries including China, Italy, South Korea, Singapore, United Kingdom(UK), United States(US), and the special administrative region of Hong Kong. All articles, press releases, and websites of government entities published over a five-month period were included. A comparison of the date of the first diagnosed case, the spread of disease, and time since the first case and major public health policy implemented for prevention and containment and current cases was done. An emphasis on early and aggressive border restriction and surveillance of travelers from infected areas, use of information technology, and social distancing is necessary for control of the novel pandemic. Moving forwards, improvement in infrastructure, and adequate preparedness for pandemics is required.

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