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Reduction of viral load by HCQ. Upon glycosylation, angiotensin converting enzyme 2 (ACE2) translocates to the membrane. SARS-CoV2 uses the glycosylated ACE2 receptor to enter into the cell. The fusion of viral and endosomal membranes leading to the release of the viral genome into the cytosol occurs at acidic pH. The genomic RNA is translated to proteins to assemble copies of the virus followed by exocytosis of SARS-CoV2 and infection of neighboring cells. HCQ inhibits the glycosylation of ACE2 receptors and increases the pH to prevent the fusion of viral and endosomal membrane
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Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much...
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The coronavirus disease 2019 (COVID-19) has become a global pandemic, which is induced by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with systemic lupus erythematosus (SLE) are susceptible to infections due to the chronic use of immunosuppressive drugs and the autoimmune disorders. Now we report a case of SL...
Citations
... Higher levels of estrogen-regulated ACE2 receptors in women play a protective role against lung injury, while the TMPRSS2 gene is regulated by an androgenresponsive promoter. In addition, estrogen promotes both innate and acquired immune responses, whereas testosterone suppresses immune function and counteracts estrogeninfluenced pathways, potentially leading to greater susceptibility to infectious diseases in men [39,40]. Furthermore, female hormones contribute to a protective effect on ocular vascularization when vascular resistance in the large vessels of the eye is reduced [41,42]. ...
Background and objectives: We aimed to investigate changes in the radial peripapillary capillary (RPC) network using optical coherence tomography angiography (OCTA) in patients who recovered from coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study of patients hospitalized due to COVID-19 bilateral pneumonia between March and May 2021. The control group included healthy individuals matched for age and sex. Two months after discharge, the patients underwent ophthalmological examination, including optical coherence tomography (OCT) imaging. The RPC network and retinal nerve fiber layer (RNFL) of the optic disc (RNFL optic disc) were automatically evaluated and compared between the study groups. Additionally, the RPC parameters were compared between the men and women in the COVID-19 group, and correlations between the RPC and RNFL optic disc parameters were assessed. Results: A total of 63 patients (120 eyes) with bilateral pneumonia caused by severe acute respiratory syndrome coronavirus 2 infection were examined. No ophthalmic symptoms were reported by the patients. No significant differences were observed in the RPC parameters between the patients from the COVID-19 group and the 43 healthy controls. Moreover, the RPC parameters did not differ between the men and women in the COVID-19 group. A positive correlation was found between the RPC and RNFL optic disc parameters in the COVID-19 patients (p < 0.001). Conclusions: No changes in the RPC network were observed among the patients with COVID-19 bilateral pneumonia in the early period after hospital discharge. However, a longer follow-up is needed to monitor COVID-19–related changes in the microvasculature of the optic nerve head.
... Also, Bialek et al., (2020) report that SARS-COV-2 occurs more frequently in old age individuals and those in high susceptibility to ICU admission and mortality in United States. The high infection rate of SARS-COV-2 among old age may be due to several comorbidities among them was observed (Pahan and Pahan, 2020). In addition to poor clinical outcome ( Wortham, 2020). ...
Acute respiratory syndrome caused by the Corona virus has spread
rapidly, conquering the world and causing the death of more than six
million people. Therefore, this study aims to isolate and diagnose the
types of fungi associated with infection with the Corona virus, determine
the causes of the disease, some symptoms, and some diseases associated
with the patients under study, as well as estimate the level of some
hematological and immunological parameters and determine the genetic
polymorphisms of some genes.
... The primary causes of higher costs were consistent across countries and included intensive care unit (ICU) admission and in-hospital resource utilization such as mechanical ventilation, which resulted in cost increases ranging from $2082. 65 ± 345.04 to $2990. 76 ± 545.98 [6]. ...
... In terms of sialic acid receptor inhibition, both CQ/HCQ were effective in inhibiting sialic acids (particularly the 9-O-SIA variant), which is required to promote SARS-CoV-2 entrance in the upper respiratory route in addition to the previously recognized ACE2 receptor [64]. Regarding the prevention of pH-mediated S protein cleavage at the ACE2 binding site, it was established that CQ/HCQ plays an important role in inhibiting glycosylation of ACE2 receptors, hence reducing SARS-CoV-2 entry into host organisms [65]. Finally, in terms of its action through the prevention of cytokine storm, HCQ inhibits the antigen processing in the antigen-presenting cells (APC) and the presentation of autoantigen mediated by the major histocompatibility complex (MHC) class II to T cells. ...
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a new coronavirus in
the Coronaviridae family. The COVID-19 pandemic, caused by SARS-CoV-2, has undoubtedly been the
largest crisis of the twenty-first century, resulting in over 6.8 million deaths and 686 million confirmed
cases, creating a global public health issue. Hundreds of notable articles have been published since
the onset of this pandemic to justify the cause of viral spread, viable preventive measures, and
future therapeutic approaches. As a result, this review was developed to provide a summary of the
current anti-COVID-19 drugs, as well as their timeline, molecular mode of action, and efficacy. It also
sheds light on potential future treatment options. Several medications, notably hydroxychloroquine
and lopinavir/ritonavir, were initially claimed to be effective in the treatment of SARS-CoV-2 but
eventually demonstrated inadequate activity, and the Food and Drug Administration (FDA) withdrew
hydroxychloroquine. Clinical trials and investigations, on the other hand, have demonstrated the
efficacy of remdesivir, convalescent plasma, and monoclonal antibodies, 6-Thioguanine, hepatitis C
protease inhibitors, and molnupiravir. Other therapeutics, including inhaled medicines, flavonoids,
and aptamers, could pave the way for the creation of novel anti-COVID-19 therapies. As future
pandemics are unavoidable, this article urges immediate action and extensive research efforts to
develop potent specialized anti-COVID-19 medications.
... Chloroquine exerts its mechanism of action by impeding the binding of the virus to angiotensinconverting enzyme 2 (ACE-2) receptors, which are utilized by SARS-CoV-2 for cellular entry. This inhibition occurs through the disruption of ACE2 receptor glycosylation [45]. Additionally, both chloroquine and hydroxychloroquine can hinder the function of sialic acid, particularly the 9-O-SIA variant [46]. ...
The cause of the COVID-19 pandemic can be attributed to the Acute Respiratory Syndrome Virus-2 (SARS-CoV-2). COVID-19 manifests with severe symptoms in the upper respiratory tract and can progress to a critical condition due to an acute hyperinflammatory response that triggers a cytokine storm. The cytokine storm refers to an excessive or impaired production of proinflammatory cytokines, resulting in immune dysregulation and uncontrolled inflammatory activity. To effectively address the hyperinflammatory state induced by SARS-CoV-2 infection, it is imperative to explore promising strategies aimed at overcoming the cytokine storm, such as the prompt initiation of anti-inflammatory therapy. Several classes of drugs can potentially prevent the deterioration of COVID-19 patients by mitigating immune system dysregulation and suppressing uncontrolled inflammatory responses. These drug classes encompass corticosteroids, chloroquine and hydroxychloroquine, inhibitors of interleukin-1 (IL-1), inhibitors of interleukin-6 (IL-6), inhibitors of tumor necrosis factor (TNF), and anti-inflammatory drugs. Additionally, tumor necrosis factor alpha (TNF-α) inhibitors, as well as inhibitors targeting the Janus kinase signaling pathway and activator of transcription (JAK/STAT), have exhibited efficacy in treating COVID-19. This efficacy is evident when considering the drug's mechanism of action and pharmacokinetics, while also taking into account the tolerable side effects associated with their usage
... Thus, it is of highest importance to study these variants and associated mutations. Until now, 12 1.529 (Omicron). Because many variants, including Delta and Omicron, evade the protection provided by available COVID-19 vaccines, we wanted to delineate whether prenol exhibited any efficacy against Delta variant SARS-CoV-2 spike S1, Alpha (N501Y) variant SARS-CoV-2 spike S1, Beta (E484K) variant SARS-CoV-2 spike S1, and Omicron variant SARS-CoV-2 spike S1 in human A549 lung cells. ...
... Accordingly, prenol also decreased the level of TNF-a in serum of SARS-CoV-2 spike S1insulted mice (Fig. 6F). Fever is possibly one of the noticeable symptoms of COVID-19 (12,13), and orally administered prenol also decreased body temperature of SARS-CoV-2 spike S1intoxicated mice (Fig. 6G). ...
Fruit consumption may be beneficial for fighting infection. Although vitamin C is the celebrity component of fruit, its role in COVID-19 is unclear. Because spike S1 of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and initiate COVID-19, using an α-screen-based assay, we screened vitamin C and other components of fruit for inhibiting the interaction between spike S1 and ACE2. We found that prenol, but neither vitamin C nor other major components of fruit (e.g., cyanidin and rutin), reduced the interaction between spike S1 and ACE2. Thermal shift assays indicated that prenol associated with spike S1, but not ACE2, and that vitamin C remained unable to do so. Although prenol inhibited the entry of pseudotyped SARS-CoV-2, but not vesicular stomatitis virus, into human ACE2-expressing HEK293 cells, vitamin C blocked the entry of pseudotyped vesicular stomatitis virus, not SARS-CoV-2, indicating the specificity of the effect. Prenol, but not vitamin C, decreased SARS-CoV-2 spike S1-induced activation of NF-κB and the expression of proinflammatory cytokines in human A549 lung cells. Moreover, prenol also decreased the expression of proinflammatory cytokines induced by spike S1 of N501Y, E484K, Omicron, and Delta variants of SARS-CoV-2. Finally, oral treatment with prenol reduced fever, decreased lung inflammation, enhanced heart function, and improved locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. These results suggest that prenol and prenol-containing fruits, but not vitamin C, may be more beneficial for fighting against COVID-19.
... 170 Interestingly, several antimalarial drugs including Hydroxychloroquine (HCQ) and Artemisininbased combination therapies (ACTs) were front-runner candidate drugs to combat COVID-19 at least during its onset. 171,172 The mechanisms of action again all infectious agents include the direct killing of microbes and their growth inhibition via the immune system. 173,174 Strong evidence has been accumulated that NO has many beneficial effects on hosts' defense against parasites including malaria protozoans but also requires tight control to limit damage to the body's cells either by cytotoxicity or by inflammation ( Figure 15). ...
Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, and erectile dysfunction. Based on NO's vast biological functions, it further can treat tumors, bacteria/biofilms and other infections, wound healing, eye diseases, and osteoporosis. However, delivering NO is challenging due to uncontrolled blood circulation release and a half-life of under five seconds. With advanced biotechnology and the development of nanomedicine, NO donors packaged with multifunctional nanocarriers by physically embedding or chemically conjugating have been reported to show improved therapeutic efficacy and reduced side effects. Herein, we review and discuss recent applications of NO nanomedicines, their therapeutic mechanisms, and the challenges of NO nanomedicines for future scientific studies and clinical applications. As NO enables the inhibition of the replication of DNA and RNA in infectious microbes, including COVID-19 coronaviruses and malaria parasites, we highlight the potential of NO nanomedicines for antipandemic efforts. This review aims to provide deep insights and practical hints into design strategies and applications of NO nanomedicines.
... They may affect any of the above-discussed mechanisms. Chloroquine phosphate, a drug that has been widely studied for treating COVID-19 is the structural analogue of quinine that is extracted from the cinchona tree bark [389]. Besides antiviral effects, it also modulates immune response [363]. ...
The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the potential available therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary approaches for countering SARS-CoV-2.
... Angiotensin converting enzyme 2 (ACE2) receptor expressing cells play an important role in the pathogenesis of SARS-CoV-2 infection, as the virus uses this receptor to enter the cell [9,[11][12][13]. HCQ impairs the terminal glycosylation of ACE2 and thereby inhibits cellbinding and entry of the virus into the cell [14][15][16]. Furthermore, HCQ also blocks transport of SARS-CoV-2 from early endosomes to endolysosomes, a requirement to release the viral genome [9,10,17]. ...
Rationale
Inhaled antimicrobials enable high local concentrations where needed and, compared to orally administration, greatly reduce the potential for systemic side effects. In SARS-CoV-2 infections, hydroxychloroquine sulphate (HCQ) administered as dry powder via inhalation could be safer than oral HCQ allowing higher and therefore more effective pulmonary concentrations without dose limiting toxic effects.
Objectives
To assess the local tolerability, safety and pharmacokinetic parameters of HCQ inhalations in single ascending doses of 5, 10 and 20 mg using the Cyclops dry powder inhaler.
Methods
Twelve healthy volunteers were included in the study. Local tolerability and safety were assessed by pulmonary function tests, electrocardiogram and recording adverse events. To estimate systemic exposure, serum samples were collected before and 0.5, 2 and 3.5 h after inhalation.
Results and discussion
Dry powder HCQ inhalations were well tolerated by the participants, except for transient bitter taste in all participants and minor coughing irritation. There was no significant change in QTc-interval or drop in FEV 1 post inhalation. The serum HCQ concentration remained below 10 μg/L in all samples.
Conclusion
Single doses of inhaled dry powder HCQ up to 20 mg are safe and well tolerated. Our data support that further studies with inhaled HCQ dry powder to evaluate pulmonary pharmacokinetics and efficacy are warranted.
... At present, two antimalarial drugs, HCQ and CQ, widely used to inhibit the fusion of autophagosomes and lysosomes, have been shown to have potential anti-SARS-CoV-2 activity and have achieved promising results in the clinical treatment of COVID-19 patients. In a multicenter clinical trial conducted in China, CQ exhibited significant efficacy and acceptable safety in COVID-19-related pneumonia[209,210]. Mechanistic studies have demonstrated that CQ destroys the endolysosome system, thereby disrupting the stability of the lysosomal membrane and leading to the intracellular release of lysosomal enzymes and an obstacle to AL fusion[211,212]. ...
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late stage of COVID-19. Here, we discuss the autophagy regulation at different stages of COVID-19. Specifically, we highlighted the therapeutic potential of autophagy activators in COVID-19 by inhibiting the NLRP3 inflammasome, thereby avoiding the cytokine storm. We hope this review provides enlightenment for the use of autophagy activators targeting the inhibition of the NLRP3 inflammasome, specifically the combinational therapy of autophagy modulators with the inhibitors of the NLRP3 inflammasome, antiviral drugs, or anti-inflammatory drugs in the fight against COVID-19.
... Hydroxychloroquine (HCQ, (RS)-2-[4-(7-Chloro-4-quinolylamino)pentyl(ethyl)amino]-ethanol) is a 4-aminoquinoline derivative [1] used as a disease-modifying anti-rheumatic drug (DMARD) [2] to treat chronic inflammatory autoimmune diseases including systemic lupus erythematosus, sarcoidosis, Sjögren's syndrome, and rheumatoid arthritis (RA), and, albeit less frequently, as antimalarial [3][4][5][6][7][8]. More recently, HCQ has also been used as a therapeutic option against COVID-19 infection [8] in view of its antiviral effects [9] and capacity to interfere with the glycosylation of SARS-CoV-2 cell receptors [10]. ...
... Hydroxychloroquine (HCQ, (RS)-2-[4-(7-Chloro-4-quinolylamino)pentyl(ethyl)amino]-ethanol) is a 4-aminoquinoline derivative [1] used as a disease-modifying anti-rheumatic drug (DMARD) [2] to treat chronic inflammatory autoimmune diseases including systemic lupus erythematosus, sarcoidosis, Sjögren's syndrome, and rheumatoid arthritis (RA), and, albeit less frequently, as antimalarial [3][4][5][6][7][8]. More recently, HCQ has also been used as a therapeutic option against COVID-19 infection [8] in view of its antiviral effects [9] and capacity to interfere with the glycosylation of SARS-CoV-2 cell receptors [10]. The daily dose ranges from 100 to 1200 mg, and after oral administration about 74% is absorbed within 4 h [11]. ...
A capillary electrophoresis method was developed to detect and measure hydroxychlo-roquine (HCQ) and its active metabolite desethyl hydroxychloroquine (DHCQ) in whole blood in patients with rheumatoid arthritis. The best separation in terms of peak area reproducibility, migration time, peak shape, and resolution of adjacent peaks was obtained in a 60 cm, 75 µm i.d. uncoated fused-silica capillary using a background electrolyte mixture of an aqueous 55 mmol/L TRIS solution brought to pH 2.6 with phosphoric acid and methanol (85:15) and a voltage and a temperature of separation of 20 kV and 30 °C, respectively. Analytes were separated in less than 12 min, with excellent linearity (R 2 ≥ 0.999) in the concentration range of 0.5-8 µmol/L. The recovery of analytes spiked in whole blood was 99-101% for HCQ and 98-99% for DHCQ. Analysis of five samples from patients with rheumatoid arthritis receiving HCQ 400 mg daily yielded mean steady-state concentrations of 2.27 ± 1.61 and 1.54 ± 0.55 µmol/L for HCQ and DHCQ, respectively, with a HCQ to DHCQ ratio of 1.40 ± 0.77.
