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Diagnostics ; 12(9):2051, 2022.
Article in English | MDPI | ID: covidwho-1997542

ABSTRACT

Coronavirus disease 2019 (COVID-19) is primarily caused by various forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants. COVID-19 is characterized by hyperinflammation, oxidative stress, multi-organ injury (MOI)-like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Different biomarkers are used in the assessment of COVID-19 severity including D-dimer, ferritin, lactate dehydrogenase (LDH), and hypoxia-inducible factor (HIF). Interestingly, growth differentiation factor 15 (GDF15) has recently become a potential biomarker correlated with the COVID-19 severity. Thus, this critical review aimed to determine the critical association between GDF15 and COVID-19. The perfect function of GDF15 remains not well-recognized;nevertheless, it plays a vital role in controlling cell growth, apoptosis and inflammatory activation. Furthermore, GDF15 may act as anti-inflammatory and pro-inflammatory signaling in diverse cardiovascular complications. Furthermore, the release of GDF15 is activated by various growth factors and cytokines including macrophage colony-stimulating factor (M-CSF), angiotensin II (AngII) and p53. Therefore, higher expression of GDF15 in COVID-19 might a compensatory mechanism to stabilize and counteract dysregulated inflammatory reactions. In conclusion, GDF15 is an anti-inflammatory cytokine that could be associated with the COVID-19 severity. Increased GDF15 could be a compensatory mechanism against hyperinflammation and exaggerated immune response in the COVID-19. Experimental, preclinical and large-scale clinical studies are warranted in this regard.

3.
Biomedicines ; 10(8):2032, 2022.
Article in English | MDPI | ID: covidwho-1997513

ABSTRACT

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions and associated local and systematic tissue damage, along with thromboembolic disorders that may increase the risk of acute ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for the vascular endothelial growth factor (VEGF), integrins, and plexins, is involved in the pathogenesis of AIS. NRP-1 is also regarded as a co-receptor for the entry of SARS-CoV-2 and facilitates its entry into the brain through the olfactory epithelium. NRP-1 is regarded as a cofactor for binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2), since the absence of ACE2 reduces SARS-CoV-2 infectivity even in presence of NRP-1. Therefore, the aim of the present study was to clarify the potential role of NRP-1 in COVID-19 patients with AIS. SARS-CoV-2 may transmit to the brain through NRP-1 in the olfactory epithelium of the nasal cavity, leading to different neurological disorders, and therefore about 45% of COVID-19 patients had neurological manifestations. NRP-1 has the potential capability to attenuate neuroinflammation, blood–brain barrier (BBB) permeability, cerebral endothelial dysfunction (ED), and neuronal dysfunction that are uncommon in COVID-19 with neurological involvement, including AIS. Similarly, high NRP-1 serum level is linked with ED, oxidative stress, and the risk of pulmonary thrombosis in patients with severe COVID-19, suggesting a compensatory mechanism to overcome immuno-inflammatory disorders. In conclusion, NRP-1 has an important role in the pathogenesis of COVID-19 and AIS, and could be the potential biomarker linking the development of AIS in COVID-19. The present findings cannot provide a final conclusion, and thus in silico, experimental, in vitro, in vivo, preclinical, and clinical studies are recommended to confirm the potential role of NRP-1 in COVID-19, and to elucidate the pharmacological role of NRP-1 receptor agonists and antagonists in COVID-19.

4.
Curr Protein Pept Sci ; 2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-1993661

ABSTRACT

In Covid-19, the pathological effect of SARS-CoV-2 infection is arbitrated through direct viral toxicity, unusual immune response, endothelial dysfunction, deregulated renin-angiotensin system [RAS], and thrombo-inflammation leading to acute lung injury [ALI], with a succession of acute respiratory distress syndrome [ARDS] in critical conditions. C1 esterase inhibitor [C1INH] is a protease inhibitor that inhibits the spontaneous activation of complement and contact systems and kinin pathway, clotting, and fibrinolytic systems. So, targeting of complement system through activation of C1INH might be a novel therapeutic modality in the treatment of Covid-19. Therefore, this study aims to illustrate the potential nexus between C1INH and the pathophysiology of SARS-CoV-2 infection. C1INH is highly dysregulated in Covid-19 due to inflammatory and coagulation disorders. C1INH is up-regulated in Covid-19 and sepsis as an acute phase response, but this increase is insufficient to block the activated complement system. In addition, the C1INH serum level predicts the development of ARDS in Covid-19 patients, as its up-regulation is associated with the development of cytokine storm. In Covid-19, C1INH might be inhibited or dysregulated by SARS-CoV-2, leading to propagation of complement system activation with subsequent uncontrolled immunological stimulation due to activation of bradykinin and FXII with sequential activation of coagulation cascades and polymerization of fibrin. Thus, suppression of C1INH by SARS-CoV-2 infection leads to thrombosis and excessive inflammation due to uncontrolled activation of complements and contact systems.

5.
Endocr Metab Immune Disord Drug Targets ; 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1987305

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by a severe acute respiratory distress syndrome, coronavirus type 2 (SARS-CoV-2), leading to acute tissue injury and an overstated immune response. In COVID-19, there are noteworthy changes in the fibrinolytic system with the development of coagulopathy. Therefore, modulation of the fibrinolytic system may affect the course of COVID-19. Tranexamic acid (TXA) is an anti-fibrinolytic drug that reduces the conversion of plasminogen to plasmin, which is necessary for SARS-CoV-2 infectivity. In addition, TXA has anti-inflammatory, anti-platelet, and anti-thrombotic effects, which may attenuate the COVID-19 severity. Thus, in this narrative review, we try to find the beneficial and harmful effects of TXA in COVID-19.

6.
Curr Drug Targets ; 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1987282

ABSTRACT

Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immuno-inflammatory abnormality, and deregulation of the renin-angiotensin system (RAS) may increase sympathetic discharge with dysautonomia development. Direct SARS-CoV-2 cytopathic effects and associated inflammatory reaction may lead to neuroinflammation, affecting different parts of the central nervous system (CNS), including the autonomic center in the hypothalamus, causing dysautonomia. High circulating AngII and hypoxia, oxidative stress, high pro-inflammatory cytokines, and emotional stress can also provoke autonomic deregulation and high sympathetic outflow with the development of the sympathetic storm. During SARS-CoV-2 infection with neuro-invasion, GABA-ergic neurons and nicotinic acetylcholine receptor (nAChR) are inhibited in the hypothalamic pre-sympathetic neurons leading to sympathetic storm and dysautonomia. Different therapeutic modalities are applied to treat SARS-CoV-2 infection, like antiviral and anti-inflammatory drugs. One robust repurposed one is Ivermectin (IVM), widely used to prevent and manage mild-moderate Covid-19. IVM activates both GABA-ergic neurons and nAChRs to mitigate SARS-CoV-2 infection-induced dysautonomia. Therefore, in this brief report, we try to identify the potential role of IVM in the management of Covid-19-induced dysautonomia.

7.
Inflamm Res ; 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1976794

ABSTRACT

INTRODUCTION: Fenofibrate is an agonist of peroxisome proliferator activated receptor alpha (PPAR-α), that possesses anti-inflammatory, antioxidant, and anti-thrombotic properties. Fenofibrate is effective against a variety of viral infections and different inflammatory disorders. Therefore, the aim of critical review was to overview the potential role of fenofibrate in the pathogenesis of SARS-CoV-2 and related complications. RESULTS: By destabilizing SARS-CoV-2 spike protein and preventing it from binding angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 entry, fenofibrate can reduce SARS-CoV-2 entry in human cells Fenofibrate also suppresses inflammatory signaling pathways, which decreases SARS-CoV-2 infection-related inflammatory alterations. In conclusion, fenofibrate anti-inflammatory, antioxidant, and antithrombotic capabilities may help to minimize the inflammatory and thrombotic consequences associated with SARSCoV-2 infection. Through attenuating the interaction between SARS-CoV-2 and ACE2, fenofibrate can directly reduce the risk of SARS-CoV-2 infection. CONCLUSIONS: As a result, fenofibrate could be a potential treatment approach for COVID-19 control.

8.
Inflammopharmacology ; 2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-1971761

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) has been identified as the source of a world coronavirus pandemic in 2019. Covid-19 is considered a main respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Although, extrapulmonary manifestations of Covid-19 like neurological, cardiovascular, and gastrointestinal have been confirmed. Exaggerated immune response and release of a high amount of pro-inflammatory cytokines may progress, causing a cytokine storm. Consequently, direct and indirect effects of SARS-CoV-2 infection can evolve into systemic complications due to the progression of hyper inflammation, oxidative stress and dysregulation of the renin-angiotensin system (RAS). Therefore, anti-inflammatory and antioxidant agents could be efficient in alleviating these disorders. Ursolic acid has anti-inflammatory, antioxidant, and antiviral effects; it reduces the release of pro-inflammatory cytokines, improves anti-inflammatory cytokines, and inhibits the production of reactive oxygen species (ROS). In virtue of its anti-inflammatory and antioxidant effects, ursolic acid may minimize SARS-CoV-2 infection-induced complications. Also, by regulating RAS and inflammatory signaling pathways, ursolic acid might effectively reduce the development of ALI in ARDS in Covid-19. In this state, this perspective discusses how ursolic acid can mitigate hyper inflammation and oxidative stress in Covid-19.

9.
Ann Hematol ; 101(9): 1887-1895, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1926021

ABSTRACT

COVID-19 is a global pandemic triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 entry point involves the interaction with angiotensin-converting enzyme 2 (ACE2) receptor, CD147, and erythrocyte Band3 protein. Hemolytic anemia has been linked to COVID-19 through induction of autoimmune hemolytic anemia (AIHA) caused by the formation of autoantibodies (auto-Abs) or directly through CD147 or erythrocyte Band3 protein-mediated erythrocyte injury. Here, we aim to provide a comprehensive view of the potential mechanisms contributing to hemolytic anemia during the SARS-CoV-2 infection. Taken together, data discussed here highlight that SARS-CoV-2 infection may lead to hemolytic anemia directly through cytopathic injury or indirectly through induction of auto-Abs. Thus, as SARS-CoV-2-induced hemolytic anemia is increasingly associated with COVID-19, early detection and management of this condition may prevent the poor prognostic outcomes in COVID-19 patients. Moreover, since hemolytic exacerbations may occur upon medicines for COVID-19 treatment and anti-SARS-CoV-2 vaccination, continued monitoring for complications is also required. Given that, intelligent nanosystems offer tools for broad-spectrum testing and early diagnosis of the infection, even at point-of-care sites.


Subject(s)
Anemia, Hemolytic , COVID-19 , Anemia, Hemolytic/etiology , COVID-19/complications , COVID-19/drug therapy , Humans , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2
10.
Frontiers in medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1918714

ABSTRACT

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses, including the coronavirus, is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2 that is currently ravaging the world. It is therefore necessary to evaluate individual chemicals of the plant for inhibitory potential against SARS-CoV-2 for the purpose of designing drugs for the treatment of COVID-19. In this study, we employed computational techniques comprising molecular docking, binding free energy calculations, pharmacophore modeling, induced-fit docking, molecular dynamics simulation, and ADMET predictions to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, isokaempferide, kaempferol, quercimeritrin, apigenin, penduletin, isoquercitrin, astragalin, luteolin-7-glucoside, and isorhamnetin were ranked the highest, with docking scores ranging from −7.84 to −7.15 kcal/mol compared with the −6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide, and kaempferol, like the standard ligand, interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. Rhamnocitrin demonstrated good stability in the active site of the protein as there were no significant conformational changes during the simulation process. These compounds also possess acceptable druglike properties and a good safety profile. Hence, they could be considered for experimental studies and further development of drugs against COVID-19.

11.
Frontiers in medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1918490

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by a novel virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2-induced hyperinflammation together with alteration of plasma proteins, erythrocyte deformability, and platelet activation, may affect blood viscosity. Thus, this review aimed to study the link between SARS-CoV-2 infection and alteration of blood viscosity in COVID-19 patients. In order to review findings related to hyperviscosity in COVID-19, we suggested a protocol for narrative review of related published COVID-19 articles. Hyperviscosity syndrome is developed in different hematological disorders including multiple myeloma, sickle cell anemia, Waldenstorm macroglobulinemia, polycythemia, and leukemia. In COVID-19, SARS-CoV-2 may affect erythrocyte morphology via binding of membrane cluster of differentiation 147 (CD147) receptors, and B and 3 proteins on the erythrocyte membrane. Variations in erythrocyte fragility and deformability with endothelial dysfunction and oxidative stress in SARS-CoV-2 infection may cause hyperviscosity syndrome in COVID-19. Of interest, hyperviscosity syndrome in COVID-19 may cause poor tissue perfusion, peripheral vascular resistance, and thrombosis. Most of the COVID-19 patients with a blood viscosity more than 3.5 cp may develop coagulation disorders. Of interest, hyperviscosity syndrome is more commonly developed in vaccine recipients who had formerly received the COVID-19 vaccine due to higher underlying immunoglobulin concentrations, and only infrequently in those who have not received the COVID-19 vaccine. Taken together, these observations are untimely too early to give a final connotation between COVID-19 vaccination and the risk for development of hyperviscosity syndrome, consequently prospective and retrospective studies are necessary in this regard.

12.
Curr Protein Pept Sci ; 2022 Jun 28.
Article in English | MEDLINE | ID: covidwho-1910825

ABSTRACT

Natriuretic peptide system [NPS] is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], and natriuretic peptide precursor C [NPC], that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is also produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase [NEP], also known as neprilysin. Coronavirus disease 2019 [Covid-19] pandemic may lead to acute lung injury [ALI] and/or respiratory distress syndrome [ARDS]. The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of a pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in the management of Covid-19.

13.
Sci Rep ; 12(1): 10494, 2022 Jun 21.
Article in English | MEDLINE | ID: covidwho-1900649

ABSTRACT

Mucormycosis is a life-threatening opportunistic angioinvasive fungal infection. We aimed to describe the frequency, presentations, predictors, and in-hospital outcome of mucormycosis patients in the scope of CoronaVirusDisease-19 (COVID-19) during the third viral pandemic wave. This cross-sectional retrospective study included all patients who fulfilled the criteria of mucormycosis with concurrent confirmed covid19 infection admitted to Assuit University Hospital between March 2021 and July 2021. Overall, 433 patients with definite covid-19 infection, of which 33 (7.63%) participants were infected with mucormycosis. Mucormycosis was predominantly seen in males (21 vs. 12; p = 0.01). Diabetes mellitus (35% vs. 63.6%; p < 0.001), hypertension (2% vs.45.5%; p 0.04), and Smoking (26.5% vs. 54.5%; p < 0.001) were all significantly higher in mucormycosis patients. Inflammatory markers, especially E.S.R., were significantly higher in those with mucormycosis (p < 0.001). The dose of steroid intake was significantly higher among patients with mucormycosis (160 mg vs. 40 mg; p < 0.001). Except for only three patients alive by residual infection, 30 patients died. The majority (62%) of patients without mucormycosis were alive. Male sex; Steroid misuse; D.M.; Sustained inflammation; Severe infection were significant risk factors for mucormycosis by univariate analysis; however, D.M.; smoking and raised E.S.R. were predictors for attaining mucormycosis by multivariate analysis.


Subject(s)
COVID-19 , Mucormycosis , Cross-Sectional Studies , Hospitals, University , Humans , Male , Mucormycosis/epidemiology , Mucormycosis/microbiology , Retrospective Studies
14.
Curr Protein Pept Sci ; 2022 Jun 10.
Article in English | MEDLINE | ID: covidwho-1892473

ABSTRACT

The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and associated hyper-inflammatory due to exaggerated immune response. Different experimental and clinical studies revealed that other biomarkers could be used to determine the Covid-19 severity, such as D-dimer, procalcitonin, C-reaction protein (CRP), IL-6, and ferritin. Calprotectin (CP) is associated with intestinal inflammation, intestinal injury, and different respiratory diseases such as cystic fibrosis. Thus, CP might be a possible biomarker linking intestinal injury and acute lung injury (ALI) in Covid-19. Therefore, this study aimed to find a potential role of CP regarding GITI and ALI in Covid-19. CP is a complex protein consisting of S100A8 and S100A9, belongs to the Ca+2-binding proteins S100 family abundant in the cytosol of neutrophils and expressed on the monocyte membranes, macrophages, and intestinal epithelial cells. CP is a proinflammatory protein that acts through activation of the receptor for the advanced glycation end product (RAGE) and toll-like receptor 4 (TLR4). CP is a biomarker of neutrophil activation and is released following the turnover of neutrophils. CP could be controversial; it increases airway inflammation or protects lung and airway epithelium from an exaggerated immune response. Therefore, a high level of CP in different respiratory disorders might be protective and compensate against abnormal immune responses. CP level is high in Covid-19 and correlated with Covid-19 severity and oxygen demand due to activation release of proinflammatory cytokines and inflammatory signaling pathways. Therefore, CP level is elevated in both ALI and intestinal inflammation so that it could be a potential biomarker link the respiratory and intestinal injury in Covid-19.

15.
Future Sci OA ; 8(5): FSO797, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1879356

ABSTRACT

Vinpocetine (VPN) is an alkaloid derivative of vincamine inhibits phosphodiesterase type 1 that increase cyclic guanosine monophosphate and cyclic adenosine monophosphate. VPN have anti-inflammatory and antioxidant effects with suppression release of pro-inflammatory cytokines. Moreover, VPN mitigates oxidative stress (OS) and inflammatory reactions through inhibition of mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, VPN may decrease hyper-inflammation-induced acute lung injury in COVID-19 through modulation of NF-κB pathway. Taken together, VPN has pulmonary and extra-pulmonary protective effects against COVID-19 through mitigation of OS and hyperinflammation. In conclusion, VPN has noteworthy anti-inflammatory and anti-oxidant effects through inhibition of NF-κB/MAPK signaling pathway so, it may reduce SARS-CoV-2-induced hyper inflammatory and OS.

16.
Arch Pharm (Weinheim) ; : e2200188, 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-1877557

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is linked with inflammatory disorders and the development of oxidative stress in extreme cases. Therefore, anti-inflammatory and antioxidant drugs may alleviate these complications. Ginkgo biloba L. folium extract (EGb) is a herbal medicine containing various active constituents. This review aims to provide a critical discussion on the potential role of EGb in the management of coronavirus disease 2019 (COVID-19). The antiviral effect of EGb is mediated by different mechanisms, including blocking SARS-CoV-2 3-chymotrypsin-like protease that provides trans-variant effectiveness. Moreover, EGb impedes the development of pulmonary inflammatory disorders through the diminution of neutrophil elastase activity, the release of proinflammatory cytokines, platelet aggregation, and thrombosis. Thus, EGb can attenuate the acute lung injury and acute respiratory distress syndrome in COVID-19. In conclusion, EGb offers the potential of being used as adjuvant antiviral and symptomatic therapy. Nanosystems enabling targeted delivery, personalization, and booster of effects provide the opportunity for the use of EGb in modern phytotherapy.

17.
Inflammopharmacology ; 30(3): 799-809, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1872585

ABSTRACT

The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up-regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute lung injury and acute respiratory distress syndrome. Different repurposed had been in use in the management of Covid-19, one of these agents is pentoxifylline (PTX) which has anti-inflammatory and antioxidant properties. Therefore, the objective of the present mini-review is to highlight the potential role of PTX in Covid-19 regarding its anti-inflammatory and antioxidant effects. PTX is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate which stimulates protein kinase A and inhibits leukotriene and tumor necrosis factor. PTX has antiviral, anti-inflammatory and immunomodulatory effects, thus it may attenuate SARS-CoV-2-induced hyperinflammation and related complications. As well, PTX can reduce hyper-viscosity and coagulopathy in Covid-19 through increasing red blood cell deformability and inhibition of platelet aggregations. In conclusion, PTX is a non-selective phosphodiesterase drug, that has anti-inflammatory and antioxidant effects thereby can reduce SARS-CoV-2 infection-hyperinflammation and oxidative stress. Besides, PTX improves red blood cells (RBCs) deformability and reduces blood viscosity so can mitigate Covid-19-induced hyper-viscosity and RBCs hyper-aggregation which is linked with the development of coagulopathy. Taken together, PTX seems to be an effective agent against Covid-19 severity.


Subject(s)
COVID-19 , Pentoxifylline , Angiotensin-Converting Enzyme 2 , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome , Humans , Pentoxifylline/pharmacology , Pentoxifylline/therapeutic use , SARS-CoV-2
18.
J Biomol Struct Dyn ; : 1-23, 2022 May 28.
Article in English | MEDLINE | ID: covidwho-1868137

ABSTRACT

The inhibition of capping enzymes such as guanine-N7-methyltransferase (GMT) is an attractive target for regulating viral replication, transcription, virulence, and pathogenesis. Thus, compounds that target the Severe Acute Respiratory Syndrome Corona Virus 2 GMT (S2GMT) will enhance drug development against COVID-19. In this study, an in-house library of 249 phytochemicals from African medicinal plants was screened using computational approaches including homology modeling, molecular docking, molecular dynamic simulations, binding free energy calculations based on molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) and Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) analysis for inhibitors of S2GMT. The top-ten ranked phytochemicals (TTRP) obtained from the docking analysis to S2GMT were further docked to SARS-COV N7-MTase. Among the TTRP, the top-four ranked phytocompounds (TFRP) viz: 3 alkaloids (Isocryptolepine, 10'-Hydroxyusambarensine and Isostrychnopentamine) and a flavonoid (Mulberrofuran F) interacted strongly with critical catalytic residues whose interference either reduce or completely abolish N7-MTase activity, indicating their potential as capping machinery disruptors. The interactions of TFRP with the catalytic residues of S2GMT were preserved in a 100 ns simulated dynamic environment, thereby, demonstrating high degree of structural stability. The MMPBSA binding free energy calculations corroborated the docking scores with biscryptolepine having the highest binding free energy to S2GMT. The TFRP showed favourable drug-likeness and ADMET properties over a wide range of molecular descriptors. Therefore, the TFRP can be further explored as potential S2GMT inhibitors in in vitro and in vivo experiments.Communicated by Ramaswamy H. Sarma.

19.
Clin Exp Med ; 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1859012

ABSTRACT

Hyperviscosity syndrome (HVS) recently emerged as a complication of coronavirus disease 2019 (COVID-19) and COVID-19 vaccines. Therefore, the objectives of this critical review are to establish the association between COVID-19 and COVID-19 vaccines with the development of HVS. HVS may develop in various viral infections due to impairment of humoral and cellular immunity with elevation of immunoglobulins. COVID-19 can increase blood viscosity (BV) through modulation of fibrinogen, albumin, lipoproteins, and red blood cell (RBC) indices. HVS can cause cardiovascular and neurological complications in COVID-19 like myocardial infarction (MI) and stroke. HVS with or without abnormal RBCs function in COVID-19 participates in the reduction of tissue oxygenation with the development of cardio-metabolic complications and long COVID-19. Besides, HVS may develop in vaccine recipients with previous COVID-19 due to higher underlying Ig concentrations and rarely without previous COVID-19. Similarly, patients with metabolic syndrome are at the highest risk for propagation of HVS after COVID-19 vaccination. In conclusion, COVID-19 and related vaccines are linked with the development of HVS, mainly in patients with previous COVID-19 and underlying metabolic derangements. The possible mechanism of HVS in COVID-19 and related vaccines is increasing levels of fibrinogen and immunoglobulins. However, dehydration, oxidative stress, and inflammatory reactions are regarded as additional contributing factors in the pathogenesis of HVS in COVID-19. However, this critical review cannot determine the final causal relationship between COVID-19 and related vaccines and the development of HVS. Prospective and retrospective studies are warranted in this field.

20.
Journal of Chemistry ; : 1-19, 2022.
Article in English | Academic Search Complete | ID: covidwho-1846584

ABSTRACT

The SARS-CoV-2 Omicron variant has spread rapidly and is considered the predominant variant in the world, and its main characteristic is related to evade immunity from natural infection or vaccines, due to its multiple mutations in the spike protein. On the other hand, medicinal plants have been used as alternatives therapies to ameliorate some signs and symptoms in COVID-19, and in our previous work, the cat's claw (Uncaria tomentosa) stem bark has been studied in vitro and showed antiviral activity on SARS-CoV-2 as well as in silico studies on the 3CLpro protein and as disruptor between the ACE-2 human receptor and the spike protein. The aim in this computational study was to determine the main phytochemical constituents from U. tomentosa stem bark against the SARS-CoV-2 Omicron spike protein based on molecular modeling. A molecular docking was carried out on the isolated phytochemicals in a previous work against the SARS-CoV-2 Omicron spike protein-binding domain (PDB ID: 7T9K). Next, a molecular dynamic study was carried out to monitor the stability during the MD simulations. As results proanthocyanidin-C1 (-10.76 kcal/mol), quinovic acid-type 2 (-9.86 kcal/mol), and proanthocyanidin-B2 (-9.82 kcal/mol) were the constituents with the best binding free energy on the SARS-CoV-2 Omicron spike protein, and the best compound was stable during the dynamic simulation under physiological conditions. It is concluded that the anthocyanidin-based compounds determined in the stem bark ethanol extract could be responsible for the potential antiviral activity on SARS-CoV-2 Omicron variant, and the proanthocyanidin-C1 emerged as a powerful candidate to combat new variants. [ FROM AUTHOR] Copyright of Journal of Chemistry is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

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