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Coronaviruses (CoVs) are positive-sense single-stranded RNA viruses with the largest known genomes among RNA viruses (27-34 kb). CoVs constitute the subfamily Orthocoronavirinae, in the family Coronaviridae. The name coronavirus is derived from the Latin word corona, meaning crown or halo, which can be seen under an electron microscope.
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CpG dinucleotides are under-represented in the genomes of single stranded RNA viruses, and coronaviruses, including SARS-CoV-2, are no exception to this. Artificial modification of CpG frequency is a valid approach for live attenuated vaccine development, and if this is to be applied to SARS-CoV-2, we must first understand the role CpG motifs play...
Citations
... PI3K pathway is intricate in different cellular functions including cell growth, differentiation, proliferation, and inhibition of autophagy. [121][122][123][124][125] Therefore, PI3K inhibitors like ceramide increase the expression of Beclin-1 and improve autophagy function. 126 Sphingosine-1-phosphate, like ceramide, promotes autophagy in many cancer cell lines. ...
Type 2 diabetes (T2D) is a chronic metabolic disorder caused by defective insulin signaling, insulin resistance, and impairment of insulin secretion. Autophagy is a conserved lysosomal‐dependent catabolic cellular pathway involved in the pathogenesis of T2D and its complications. Basal autophagy regulates pancreatic β‐cell function by enhancing insulin release and peripheral insulin sensitivity. Therefore, defective autophagy is associated with impairment of pancreatic β‐cell function and the development of insulin rersistance (IR). However, over‐activated autophagy increases apoptosis of pancreatic β‐cells leading to pancreatic β‐cell dysfunction. Hence, autophagy plays a double‐edged sword role in T2D. Therefore, the use of autophagy modulators including inhibitors and activators may affect the pathogenesis of T2D. Hence, this review aims to clarify the potential role of autophagy inhibitors and activators in T2D.
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... NO suppresses ALI by reducing fibrin deposition and lung inflammation [141]. Therefore, PDE5 Inhibitors can be used as a preventive option for common AngII-induced COVID complications [142,143]. (26) According to multiple studies conducted in animal models, PDE5 Inhibitors can improve immunity in mice. ...
Introduction
Despite the ever-increasing occurrences of the coronavirus disease (COVID-19) cases around the world, very few medications have been validated in the clinical trials to combat COVID-19. Although several vaccines have been developed in the past quarter, the time elapsed between deployment and administration remains a major impediment.
Content
Repurposing of pre-approved drugs, such as phosphodiesterase 5 (PDE5) inhibitors, could be a game-changer while lessening the burden on the current healthcare system. Repurposing and developing phosphodiesterase 5 (PDE5) inhibitors could extrapolate their utility to combat the SARS-CoV-2 infection, and potentially aid in the management of the symptoms associated with its newer variants such as BF.7, BQ.1, BQ.1.1, XBB.1.5, and XBB.1.16.
Summary
Administration of PDE5 inhibitors via the oral and intravenous route demonstrates other potential off-label benefits, including anti-apoptotic, anti-inflammatory, antioxidant, and immunomodulatory effects, by intercepting several pathways. These effects can not only be of clinical importance in mild-to-moderate, but also moderate-to-severe SARS-CoV-2 infections. This article explores the various mechanisms by which PDE5 inhibitors alleviates the symptoms associated with COVID-19 as well as well as highlights recent studies and findings.
Outlook
These benefits of PDE5 inhibitors make it a potential drug in the physicians’ armamentarium in alleviating symptoms associated with SARS-CoV-2 infection. However, adequate clinical studies must be instituted to eliminate any untoward adverse events.
... NO suppresses ALI by reducing fibrin deposition and lung inflammation [141]. Therefore, PDE5 Inhibitors can be used as a preventive option for common AngII-induced COVID complications [142,143]. (26) According to multiple studies conducted in animal models, PDE5 Inhibitors can improve immunity in mice. ...
Introduction:
Despite the ever-increasing occurrences of the coronavirus disease (COVID-19) cases around the world, very few medications have been validated in the clinical trials to combat COVID-19. Although several vaccines have been developed in the past quarter, the time elapsed between deployment and administration remains a major impediment.
Content:
Repurposing of pre-approved drugs, such as phosphodiesterase 5 (PDE5) inhibitors, could be a game-changer while lessening the burden on the current healthcare system. Repurposing and developing phosphodiesterase 5 (PDE5) inhibitors could extrapolate their utility to combat the SARS-CoV-2 infection, and potentially aid in the management of the symptoms associated with its newer variants such as BF.7, BQ.1, BQ.1.1, XBB.1.5, and XBB.1.16.
Summary:
Administration of PDE5 inhibitors via the oral and intravenous route demonstrates other potential off-label benefits, including anti-apoptotic, anti-inflammatory, antioxidant, and immunomodulatory effects, by intercepting several pathways. These effects can not only be of clinical importance in mild-to-moderate, but also moderate-to-severe SARS-CoV-2 infections. This article explores the various mechanisms by which PDE5 inhibitors alleviates the symptoms associated with COVID-19 as well as well as highlights recent studies and findings.
Outlook:
These benefits of PDE5 inhibitors make it a potential drug in the physicians' armamentarium in alleviating symptoms associated with SARS-CoV-2 infection. However, adequate clinical studies must be instituted to eliminate any untoward adverse events.
... Downregulation of ACE2 by SARS-Co-2 augments the elevation of AngII, which has pro-inflammatory and proliferative effects ( Figure 1). 6 Covid-19 is linked with the development of cardiometabolic disorders, including dyslipidemia in general and in a particular dysregulation of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). 7 Different human studies illustrated that SARS-Co-2 infection is linked with significant changes in lipid profile, which was suggested as a possible biomarker to support the diagnosis and management of Covid-19. ...
Introduction:
Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia, dysregulation of high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Furthermore, SARS-Co-2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid-19.
Methods:
This paper adopts the literature review method to obtain information about how Covid-19 affects high-risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented.
Results:
Reducing HDL in Covid-19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid-19. SARS-CoV-2 binds HDL, and this complex is attached to the co-localized receptors, facilitating viral entry. Therefore, SARS-CoV-2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid-19 severity.
Conclusions:
Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia in general and dysregulation of high-density lipoprotein and low-density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high-density lipoprotein and Covid-19.
... The current devastating coronavirus disease 2019 (COVID-19) pandemic leads to a worldwide impact with high morbidity and relative mortality in high-risk group patients [1]. The COVID-19 is caused by a novel single-strand RNA virus named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [2,3]. ...
Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms
described as “long-COVID” or “Post-COVID syndrome” (PCS). Patients may have persisting symptoms for weeks after
acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These
symptoms may last for months in some patients. PCS may progress in association with the development of mast cell
activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation
of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women,
and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are
more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated
with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS.
PCS has systemic manifestations that resolve with time with no further complications. However, the fnal outcomes of
PCS are chiefy unknown. Persistence of infammatory reactions, autoimmune mimicry, and reactivation of pathogens
together with host microbiome alterations may contribute to the development of PCS. The deregulated release of
infammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS
during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore,
MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition
of degranulation of mast cells
... Clinical pathological investigations of lung biopsies and dissections of COVID-19 patients demonstrate alveolar discharge along small vessel clots arrangement around the lung periphery 103,104 . Alveolar Hemorrhage is a typical component of the acute respiratory distress syndrome (ARDS), a condition related with COVID-19. ...
Abstract. – OBJECTIVE: With the recent direction in drug repurposing, many approved
drugs have been evaluated to assess their effect on the coronavirus or SARS-CoV-2 infection (COVID-19). Driving this path, chloroquine (CQ) has been used in the treatment of malaria and hydroxychloroquine (HCQ) in immunomodulatory and anti-thrombotic action, playing a leading role in the initial management of the viral infection.
MATERIALS AND METHODS: A literature search was done using Google Scholar, PubMed, and Scopus database using keywords “chloroquine” “SARS-CoV-2” “COVID-19” “mechanism of action” and articles of interest were selected providing evidence of the possible role of CQ in viral infection.
RESULTS: In a bid to understand how and if CQ and HCQ would exert their anti-viral property, mechanistic exegesis was done to review various proposed mechanisms of action. This revealed the inhibition of viral attachment and entry, inhibition of enveloped glycoprotein, inhibition of the development and proliferation of new viral particles as the way they perform their action. There is an interplay between iron metabolism and homeostasis with COVID-19 infection and viral reproduction.
CONCLUSIONS: This study aims to show the functional role of CQ and HCQ, as well as to provide possible mechanistic insight on the role of iron on viral infection, iron starvation, and its downstream cellular pathways involving hepcidin and proinflammatory cytokines. The overall aim of providing a possible mode of action of CQ and HCQ in the management of COVID-19 infection is exhibited via its anti-viral, anti-inflammatory, and anti-thrombotic activities.
... Primary infection of SARS-CoV-2 targets specific cells, such as nasal and bronchial epithelial cells and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Besides, type 2 transmembrane serine protease (TMPRSS2), present in the host cell, promotes viral uptake by cleaving ACE2 and triggering the SARS-CoV-2 S protein, which facilitates SARS-CoV-2 entry into host cells (figure 2) [7]. ACE2 and TMPRSS2 are expressed in host target cells, predominantly alveolar epithelial type II cells. ...
Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus results in significant mortality and long-term disability. Coronavirus infectious disease 2019 (Covid-19), is caused by SARS-CoV-2 binds by glycoproteins expressed on its surface to the receptor of the angiotensin-converting enzyme 2 (ACE2), which is highly distributed in the respiratory tract epithelium. ACE2 is highly expressed on nervous tissue cells like neurons and astrocytes. Once inside the nerve cell, SARS-CoV-2 can alter the cellular transport function to facilitate its transmission from one neuron to another. Upon infection and because of other forms of damage neuroglial cells become reactive, representing the most classic neuro-pathological situation of the ongoing neuro-inflammation. Consequently, it is likely that the SARS‐CoV‐2 infected brain regions triggers reactive astrogliosis and activation of microglia. The mechanism of involvement of peripheral nervous system is not fully understood. It is mostly thought to be immune-mediated. In patients with rapid evolution of Guillain-Barrè syndrome (GBS) after the onset of COVID-19 symptoms, direct cytotoxic effects of virus on peripheral nerves is a postulated mechanism.
... This virus is usually 0.06-0.14 µm in diameter and displays a crown-like appearance under an electron microscope with spike-like projections on the surface resulting in having the name 'coronavirus' (Latin 'corona' means crown) (Al-Kuraishy and Al-Gareeb, 2020;Singhal, 2020). This disease, with a mean incubation time of 6.5 days, attacks people of all ages being transmitted via cough-and sneeze-generated large droplets from both symptomatic and asymptomatic patients and the virus in these droplets on the surface can remain infectious for days but becomes non-infectious in the presence of regular disinfectants (Hoehl et al., 2020;Kampf et al., 2020;Lai et al., 2020;Rothe et al., 2020). ...
The COVID-19 disease has triggered the death of millions of people worldwide and has been the cause of 4,281 deaths in Bangladesh since 8th March 2020 till 31st August 2020. This cross-sectional study was aimed at discerning the pattern of COVID-19 among the people of this country the testing response, the recovery pattern of the patients and the effect of co-existing conditions on their recovery. An online questionnaire was made and distributed among 565 randomly selected patients for their responses and statistical analysis was performed on those responses. Each participant described multiple symptoms and the most frequently described symptoms were fever, cough and loss of smell (described by 446, 225 and 171 participants, respectively). The majority of the participants (47.16) received their test reports within 3 to 5 days whereas 27.01, 10.76 and 15.07% participants got their reports within 1-2 , 6-10 and in more than 10 days, respectively and their residence area did not affect this time interval in getting the report. Overall 90% recovery rate was found which was different in different age groups being lowest in the group of people aged 70 years or more. Recovery seemed to be influenced by educational level, but not influenced by gender, residence level or professional educational background. Co-morbidities increased the likelihood of getting the disease and some of them (diabetes, hypertension, kidney diseases, cancer and HIV) interfered with the normal recovery process. More extensive studies with larger sample sizes are needed to conclusively discern the COVID-19 disease pattern among Bangladeshi people.
... Primary infection of SARS-CoV-2 targets specific cells, such as nasal and bronchial epithelial cells and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Besides, type 2 transmembrane serine protease (TMPRSS2), present in the host cell, promotes viral uptake by cleaving ACE2 and triggering the SARS-CoV-2 S protein, which facilitates SARS-CoV-2 entry into host cells (figure 2) [7]. ACE2 and TMPRSS2 are expressed in host target cells, predominantly alveolar epithelial type II cells. ...
... Primary infection of SARS-CoV-2 targets specific cells, such as nasal and bronchial epithelial cells and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor . Besides, type 2 transmembrane serine protease (TM-PRSS2), present in the host cell, promotes viral uptake by cleaving ACE2 and triggering the SARS-CoV-2 S protein, which facilitates SARS-CoV-2 entry into host cells(figure 2) [7]. ACE2 and TMPRSS2 are expressed in host target cells, predominantly alveolar epithelial type II cells. ...
