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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the world's health systems for more than two years. This disease causes a high mortality rate followed by cytokine storm–induced oxidative stress and acute respiratory distress syndrome (ARDS). Therefore, many drugs have been considered with emphasis on their anti-inflammatory and antioxidant effects in controlling the consequences of SARS-CoV-2 infection. Icariin is a major bioactive pharmaceutical compound derived from Epimedium plants, which is known due to its anti-inflammatory and antioxidant effects. Additionally, the protective effects of icariin have been studied in different pathologies through modulating intracellular pathways. In addition to the potential effect of this compound on inflammation and oxidative stress caused by SARS-CoV-2 infection, it appears to interfere with intracellular pathways involved in viral entry into the cell. Therefore, this paper aims to review the molecular mechanisms of anti-inflammatory and antioxidant properties of icariin, and hypothesizes its potential to inhibit SARS-CoV-2 entry into host cells through modulating the intracellular pathways. [ABSTRACT FROM AUTHOR]

Novel coronavirus pneumonia (COVID-19) is spreading worldwide, causing great harm and stress to humans. Since patients with novel coronavirus (SARS-CoV-2) have a high probability of developing acute respiratory distress syndrome (ARDS) in severe cases, the pathways through which SARS-CoV-2 causes lung injury have become a major concern in the scientific field. In this paper, we investigate the relationship between SARS-CoV-2 and lung injury and explore the possible mechanisms of COVID-19 in ARDS from the perspectives of angiotensin-converting enzyme 2 protein, cytokine storm, activation of the immune response, triggering of Fas/FasL signaling pathway to promote apoptosis, JAK/STAT pathway, NF-κB pathway, type I interferon, vitamin D, and explore the possibility of prevention and treatment of COVID-19. To explore the possibility of SARS-CoV-2, and to provide new ideas to stop the development of ARDS in COVID-19 patients. [ABSTRACT FROM AUTHOR]

New coronavirus disease 2019 (COVID‐19), as a pandemic disaster, has drawn the attention of researchers in various fields to discover suitable therapeutic approaches for the management of COVID‐19 patients. Currently, there are many worries about the rapid spread of COVID‐19; there is no approved treatment for this infectious disease, despite many efforts to develop therapeutic procedures for COVID‐19. Emerging evidence shows that mesenchymal stromal/stem cell (MSC) therapy can be a suitable option for the management of COVID‐19. These cells have many biological features (including the potential of differentiation, high safety and effectiveness, secretion of trophic factors and immunoregulatory features) that make them suitable for the treatment of various diseases. However, some studies have questioned the positive role of MSC therapy in the treatment of COVID‐19. Accordingly, in this paper, we will focus on the therapeutic impacts of MSCs and their critical role in cytokine storm of COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Objective: Treatment for COVID-19 is still urgent need for the critically ill and severe cases. UC-MSC administration has a therapeutic benefit for severe COVID-19 patients even in the recovery period. In this paper, we aimed to present our clinical experience with UC-MSC treatment in severe and critical severe COVID-19 patients. Methods: In this study we evaluated the clinical outcome of severe/critically severe 210 COVID-19 patients treated with UC-MSCs, 1–2 × 106 per kilogram to 210 patients from 15/10/2020 until 25/04/2021. Results: Out of 99 critically severe intubated patients we have observed good clinical progress/discharged from ICU in 52 (52.5%) patients. Where as 86 (77.5%) of 111 severe unintubated patients discharged from ICU. Intubated 47 (47.5%) patients and unintubated 25 (22.5%) patients pass away. Significantly higher survival was observed in patients who underwent UC-MSCs before intubation (OR = 1.475, 95% CI = 1.193–1.824 p < 0.001). It was observed that the SaO2 parameter tended to improve after UC-MSC therapy compared to all groups. But SaO2 parameter between intubated and unintubated groups was not statistically significant (p > 0.05), while in discharged cases SaO2 parameter was statistically significant (p = 0.01). Besides, there was a statistically significant relation with intubation status, age (OR = 3.868, 95% CI = 0.574–7.152 p = 0.02) and weigh (OR = 6.768, 95% CI = 3.423–10.112 p < 0.001) thus presented an elevated risk for COVID-19. The linear regression analysis confirmed that the high weight was associated with the risk of intubation in COVID-19 (p = 0.001). Conclusions: According to our results and from recent studies, UC-MSC treatment is safe with high potential to be used as an added therapeutic treatment for severe COVID-19 patients. Our experience showed that UC-MSC therapy may restore oxygenation and downregulate cytokine storm in patients hospitalized with severe COVID-19. We advice wider randomised studies to discover the detailed therapeutic pathophysiology of the MSCs on COVID-19 patients. MSCs transplantation improves the damaging effects of the cytokine storm through immunomodulation and improving tissue and organ repair. Severe patients who were unintubated were in the Phase I, while critical patients who were intubated were in the Phase II. The figure is created via biorender application, (BioRender.com). [ABSTRACT FROM AUTHOR]

Introduction: This systematic review and meta‐analysis aims to investigate the mutual impact of COVID‐19 and psoriasis to inform clinical practice and future research. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta‐analysis protocol for systematic reviews and searched PubMed, Web of Science, Scopus, and Google Scholar until May 1, 2022. Eligibility criteria included full‐text articles in English reporting COVID‐19 treatment outcomes in psoriasis patients. Studies on animals, letters to editors, non‐English studies, and studies with no access to full articles were excluded. Search results were screened and data were extracted by two groups of reviewers with any discrepancies resolved by the senior author. The risk of bias was assessed using ROBINS‐I for nonrandomized studies. The hospitalization rate, Intensive Care Unit (ICU) admission rate, case fatality rate, odds ratios of COVID‐19 infection and hospitalization rate in psoriasis patients were extracted and analyzed using random effects analysis to calculate pooled prevalence and odds ratios, as well as to explore heterogeneity. Results: We found 1980 records from four databases and included 20 studies after screening and removing duplicates. These studies evaluated 185,000 psoriasis patients and included eight retrospective cohort studies, one case‐control study, three cross‐sectional studies, and eight case series studies. The impact of the COVID‐19 pandemic on psoriasis treatment and the outcome of COVID‐19 infection in psoriasis patients receiving different forms of treatment were evaluated. The pooled data from included studies showed that the incidence rate of COVID‐19 infection among psoriasis patients was 0.03% (confidence interval [CI]: 0.01–0.06), with a pooled odds ratio of 1.97 (CI: 0.69–5.60) compared to the general population. The hospitalization rate, ICU admission rate, and case fatality rate for psoriasis patients with COVID‐19 were 0.17 (CI: 0.10–0.31), 0.06 (CI: 0.06–0.46), and 0.02 (CI: 0.01–0.04), respectively. Additionally, psoriasis patients receiving systemic nonbiologic therapy had a pooled odds ratio of 2.32 (CI: 1.18–4.57) for hospitalization compared to those using biologic agents. Conclusion: Studies have shown that biologic therapy for psoriasis did not increase the risk of hospitalization due to COVID‐19 infection and may have even offered some protection. Treatment adherence was higher in psoriasis patients receiving biologic therapies than those receiving conventional therapies. These findings suggest that psoriasis treatment did not negatively impact COVID‐19 infection and that treatment could be continued on a case‐by‐case basis during the pandemic. Highlights: The use of immunosuppressive treatments in patients with pre‐existing immune‐mediated diseases, such as psoriasis, who become infected with COVID‐19 is a controversial issue.COVID‐19 can cause cytokine storm in the body, which may exacerbate diseases with inflammation‐based pathophysiology.Current information about the dynamic association between COVID‐19 and pre‐existing immune‐mediated diseases, as well as the impact of COVID‐19 infection and its treatments on the course of the underlying disease, is limited and controversial.There are concerns that discontinuing or altering routine medications due to COVID‐19 may change the course of the underlying disease, and flare‐ups may occur.However, evidence suggests that biologics and nonbiologic drugs may have desirable effects on overcoming the hyperinflammation state caused by COVID‐19, and withholding biologics due to COVID‐19 infection is not advisable.Patients who had discontinued their psoriasis medications prior or after being afflicted with COVID‐19 were more likely to experience severe psoriasis flare‐ups.Patients who had not missed their scheduled biologic administration were likely to experience mild COVID‐19 symptoms while their psoriasis condition remained unchanged.Using glucocorticoids is one of the main therapeutic strategies in patients with severe COVID‐19 symptoms, but in psoriatic patients, administration of glucocorticoids during the course of COVID‐19 infection might affect the patient's psoriasis presentation. It is crucial to further investigate this matter, as there is still no general agreement.Infection with COVID‐19 does not increase the possibility of exacerbation and flare‐up of psoriasis. [ABSTRACT FROM AUTHOR]

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A “cytokine storm”, i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotidebinding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients [ABSTRACT FROM AUTHOR]

Obesity has been recognized as one of the most significant risk factors for the deterioration and mortality associated with COVID-19, but the significance of obesity itself differs among ethnicity. Multifactored analysis of our single institute-based retrospective cohort revealed that high visceral adipose tissue (VAT) burden, but not other obesity-associated markers, was related to accelerated inflammatory responses and the mortality of Japanese COVID-19 patients. To elucidate the mechanisms how VAT-dominant obesity induces severe inflammation after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, we infected two different strains of obese mice, C57BL/6JHamSlc-ob/ob (ob/ob), C57BLKS/J-db/db (db/db), genetically impaired in the leptin ligand and receptor, respectively, and control C57BL/6 mice with mouse-adapted SARS-CoV-2. Here, we revealed that VAT-dominant ob/ob mice were extremely more vulnerable to SARS-CoV-2 due to excessive inflammatory responses when compared to SAT-dominant db/db mice. In fact, SARS-CoV-2 genome and proteins were more abundant in the lungs of ob/ob mice, engulfed in macrophages, resulting in increased cytokine production including interleukin (IL)-6. Both an anti-IL-6 receptor antibody treatment and the prevention of obesity by leptin replenishment improved the survival of SARS-CoV-2-infected ob/ob mice by reducing the viral protein burden and excessive immune responses. Our results have proposed unique insights and clues on how obesity increases the risk of cytokine storm and death in patients with COVID-19. Moreover, earlier administration of antiinflammatory therapeutics including anti-IL-6R antibody to VAT-dominant patients might improve clinical outcome and stratification of the treatment for COVID-19, at least in Japanese patients. [ABSTRACT FROM AUTHOR]

The potential advantages of sleep concerning suppressing cytokine storms and inflammation in coronavirus disease 2019 (COVID-19) based on its immunopathogenesis are summarized in the current study. COVID-19 as a global pandemic in the past months has afflicted many people. Clinical properties, pathology, and the pathogenesis of acute respiratory disorder caused by coronaviruses or other pathogens are evidence implying the probable contribution of oxidation, excessive inflammation, and excessive immune response, particularly cytokine storm, to the pathology of COVID-19. According to findings by experimental and clinical research on animals and in humans, sleep loss impairs immune function. Sleep loss strongly influences peripheral levels of the immune response's inflammatory mediators, which is accomplished by the generation of various hormones and mediators during sleep. There are a large number of studies supporting the presence of reciprocal regulation between low-intensity inflammatory response and sleep. By improving sleep quality and at the same time adjusting the circadian rhythm, it may be possible to prevent infections and boost immunity. As a result, sufficient (or even more) sleep duration may lower susceptibility to COVID-19 infection as well as increase antibody levels. [ABSTRACT FROM AUTHOR]

Background. The potential role of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) pneumonia provides the rationale for investigating IL-6 signaling inhibitors. Objectives. To evaluate and report treatment responses to tocilizumab (TCZ) in COVID-19 patients and compare mortality outcomes with those of standard care. Materials and methods. Patients hospitalized with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, diagnosed with reverse transcription polymerase chain reaction (RT-PCR) between March 2020 and April 2021, were enrolled in this single-center retrospective cohort study. Propensity score matching was performed in order to reduce confounding effects secondary to imbalances in receiving TCZ treatment. Results. A total of 364 patients were included in this study. Two hundred thirty-six patients received standard care, while 128 patients were treated with TCZ in addition to standard care (26 (20.3%) patients received a dose of 400 mg intravenously once, while 102 (79.7%) patients received a total dose of 800 mg intravenously). In the propensity score-matched population, less noninvasive mechanical ventilation (p = 0.041) and mechanical ventilation support (p = 0.015), and fewer deaths (p = 0.008) were observed among the TCZ-treated patients. The multivariate adjusted Cox regression model showed a significantly higher survival rate among TCZ patients compared to controls (hazard ratio (HR): 0.157, 95% confidence interval (95% CI): 0.026--0.951; p = 0.044). The hazard ratio for mortality in the TCZ group was 0.098 (95% CI: 0.030--0.318; p = 0.0001 using log-rank test). Conclusions. This study determined that TCZ treatment in COVID-19 patients was associated with better survival, reduced need for mechanical ventilation and reduced hospital-associated mortality. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral agent that causes Coronavirus disease 2019 (COVID-19), a disease that causes flu-like symptoms that, when exacerbated, can have life-threatening consequences. COVID-19 has been linked to persistent symptoms, sequelae, and medical complications that can last months after the initial infection. This systematic review aims to elucidate the innate and adaptive immune mechanisms involved and identify potential characteristics of COVID-19 pathology that may increase symptom duration. We also describe he three different stages of COVID-19—viral replication, immune hyperactivation, and post-acute sequelae—as well as each phase's corresponding immune response. Finally, we use this multiphasic approach to describe different treatment approaches for each of the three stages—antivirals, immunosuppressants and monoclonal antibodies, and continued immunosuppressants—to fully curate the treatment to the stage of disease. [ABSTRACT FROM AUTHOR]

Background/aim: As SARS-CoV-2 continues to spread worldwide, this study brings to light the link that anakinra, a recombinant IL-1 receptor antagonist, has in averting grave clinical outcomes. The objectives of this meta-analysis are to investigate the effects of anakinra in interventional groups compared to control/standard of care groups on mortality along with the provision of a prevalence estimate of the variables associated with death (C-reactive protein-CRP, ferritin, acute respiratory distress syndrome-ARDS). Materials and methods: According to the PRISMA 2020 statement guidelines, a systematic search was conducted from December 19, 2020, until December 10, 2021, with keywords including COVID-19, coronavirus, SARS-CoV-2, anakinra, mortality, across the following databases: PubMed/MEDLINE, Scopus, Web of Science, CINAHL Plus, and Cochrane. A random-effects model was applied using RevMan 5.4 for all statistical analyses. Results: The meta-analysis pooled in 1297 participants with 565 (43.6%) patients in the anakinra group. When comparing to the control/standard of care group, the anakinra group had a much lower risk of death (RR = 0.47. 95% CI = 0.37-0.59, Z = 6.44; P < 0.001). In addition to the risk of death being reduced by around 50% in the interventional group, prognostic indicators such as CRP and ferritin were improved with fewer occurrences of severe ARDS. Conclusion: Patients with COVID-19 pneumonia may be treated with anakinra as a safe and viable treatment modality to defer adverse outcomes such as a death in the 28-day period. Despite an auspicious premise, our findings must be used with caution as adequately powered randomized, placebo-controlled trials are required to corroborate these findings. [ABSTRACT FROM AUTHOR]

Background: Cytokine storm (CS) is a systemic inflammatory syndrome and a major cause of multi-organ failure and even death in COVID-19 patients. With the increasing number of COVID-19 patients, there is an urgent need to develop effective therapeutic strategies for CS. Baicalin is an anti-inflammatory and antiviral traditional Chinese medicine. In the present study, we aimed to evaluate the therapeutic mechanism of baicalin against CS through network analysis and experimental validation, and to detect key targets of CS that may bind closely to baicalin through molecular docking. Method: Access to potential targets of baicalin and CS in public databases. We constructed the protein-protein interaction (PPI) network of baicalin and CS by Cytoscape 9.0 software and performed network topology analysis of the potential targets. Then, the hub target was identified by molecular docking technique and validated in the CS model. Finally, GO and KEGG pathway functional enrichment analysis of common targets were confirmed using R language, and the location of overlapping targets in key pathways was queried via KEGG Mapper. Result: A total of 86 overlapping targets of baicalin and CS were identified, among which MAPK14, IL2, FGF2, CASP3, PTGS2, PIK3CA, EGFR, and TNF were the core targets. Moreover, it was found that baicalin bound most closely to TNF through molecular docking, and demonstrated that baicalin can effectively inhibit the elevation of TNF-α in vitro and in vivo. Furthermore, bioenrichment analysis revealed that the TNF signaling pathway and IL-17 signaling pathway may be potential key pathways for baicalin to treat CS. Conclusion: Based on this study, baicalin was identified as a potential drug for the alleviation of CS, and the possible key targets and pathways of baicalin for the treatment of CS were elucidated to reveal the main pharmacological mechanisms. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has shaken the world and triggered drastic changes in our lifestyle to control it. Despite the non-typical efforts, COVID-19 still thrives and plagues humanity worldwide. The unparalleled degree of infection has been met with an exceptional degree of research to counteract it. Many drugs and therapeutic technologies have been repurposed and discovered, but no groundbreaking antiviral agent has been introduced yet to eradicate COVID-19 and restore normalcy. As lethality is directly correlated with the severity of disease, hospitalized severe cases are of the greatest importance to reduce, especially the cytokine storm phenomenon. This severe inflammatory phenomenon characterized by elevated levels of inflammatory mediators can be targeted to relieve symptoms and save the infected patients. One of the promising therapeutic strategies to combat COVID-19 is nucleic acid-based therapeutic approaches, including microRNAs (miRNAs). This work is an up-to-date review aimed to comprehensively discuss the current nucleic acid-based therapeutics against COVID-19 and their mechanisms of action, taking into consideration the emerging SARS-CoV-2 variants of concern, as well as providing potential future directions. miRNAs can be used to run interference with the expression of viral proteins, while endogenous miRNAs can be targeted as well, offering a versatile platform to control SARS-CoV-2 infection. By targeting these miRNAs, the COVID-19-induced cytokine storm can be suppressed. Therefore, nucleic acid-based therapeutics (miRNAs included) have a latent ability to break the COVID-19 infection in general and quell the cytokine storm in particular. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged from Wuhan in China before it spread to the entire globe. It causes coronavirus disease of 2019 (COVID-19) where mostly individuals present mild symptoms, some remain asymptomatic and some show severe lung inflammation and pneumonia in the host through the induction of a marked inflammatory 'cytokine storm'. New and efficacious vaccines have been developed and put into clinical practice in record time, however, there is a still a need for effective treatments for those who are not vaccinated or remain susceptible to emerging SARS-CoV-2 variant strains. Despite this, effective therapeutic interventions against COVID-19 remain elusive. Here, we have reviewed potential drugs for COVID-19 classified on the basis of their mode of action. The mechanisms of action of each are discussed in detail to highlight the therapeutic targets that may help in reducing the global pandemic. The review was done up to July 2021 and the data was assessed through the official websites of WHO and CDC for collecting the information on the clinical trials. Moreover, the recent research papers were also assessed for the relevant data. The search was mainly based on keywords like Coronavirus, SARS-CoV-2, drugs (specific name of the drugs), COVID-19, clinical efficiency, safety profile, side-effects etc.This review outlines potential areas for future research into COVID-19 treatment strategies. • More than one year to the COVID-19 pandemic, still no effective drug treatment exists so far. • We have summarized the drugs showing both positive effect and negative effects for their future application. • Veklury (Remdesivir) is the only FDA-approved drug for adult and pediatric patients • Chloroquine, Hydroxychloroquine, Azithromycin, colchicine and Ivermectin has been removed from the list of potential drugs. • Tocilizumab and Sarilumab has been proven to work and are currently under trials. • Though, Remdesivir has been licensed for emergency and provisional use in different countries, it is not terribly effective. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity and reliability, monoclonal antibodies (mAbs) have emerged as powerful tools to treat and detect numerous diseases. Hence, many researchers have begun to urgently develop Ab-based kits for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ab drugs for use as COVID-19 therapeutic agents. The detailed structure of the SARS-CoV-2 spike protein is known, and since this protein is key for viral infection, its receptor-binding domain (RBD) has become a major target for therapeutic Ab development. Because SARS-CoV-2 is an RNA virus with a high mutation rate, especially under the selective pressure of aggressively deployed prophylactic vaccines and neutralizing Abs, the use of Ab cocktails is expected to be an important strategy for effective COVID-19 treatment. Moreover, SARS-CoV-2 infection may stimulate an overactive immune response, resulting in a cytokine storm that drives severe disease progression. Abs to combat cytokine storms have also been under intense development as treatments for COVID-19. In addition to their use as drugs, Abs are currently being utilized in SARS-CoV-2 detection tests, including antigen and immunoglobulin tests. Such Ab-based detection tests are crucial surveillance tools that can be used to prevent the spread of COVID-19. Herein, we highlight some key points regarding mAb-based detection tests and treatments for the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19. [ABSTRACT FROM AUTHOR]

The SARS-Cov-2 virus caused a high morbidity and mortality rate disease, that is the COVID-19 pandemic. Despite the unprecedented research interest in this field, the lack of specific treatments leads to severe complications in a high number of cases. Current treatment includes antivirals, corticosteroids, immunoglobulins, antimalarials, interleukin-6 inhibitors, anti-GM-CSF, convalescent plasma, immunotherapy, antibiotics, circulation support, oxygen therapy, and circulation support. Due to the limited results, until specific treatments are available, other therapeutic approaches need to be considered. The endocannabinoid system is found in multiple systems within the human body, including the immune system. Its activation can lead to beneficial results such as decreased viral entry, decreased viral replication, and a decrease in pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, TNF-α, or IFN-γ. Moreover, endocannabinoid system activation can lead to an increase in anti-inflammatory cytokines, mainly represented by IL-10. Overall, the cannabinoid system can potentially reduce pulmonary inflammation, increase the immunomodulatory effect, decrease PMN infiltration, reduce fibrosis, and decrease viral replication, as well as decrease the 'cytokine storm'. Although the cannabinoid system has many mechanisms to provide certain benefits in the treatment of SARS-CoV-2 infected patients, research in this field is needed for a better understanding of the cannabinoid impact in this situation. [ABSTRACT FROM AUTHOR]

The inflammatory protease caspase-1 is associated with the release of cytokines. An excessive number of cytokines (a "cytokine storm") is a dangerous consequence of COVID-19 infection and has been indicated as being among the causes of death by COVID-19. The anti-inflammatory drug colchicine (which is reported in the literature to be a caspase-1 inhibitor) and the corticosteroid drugs, dexamethasone and methylprednisolone, are among the most effective active compounds for COVID-19 treatment. The SERM raloxifene has also been used as a repurposed drug in COVID-19 therapy. In this study, inhibition of caspase-1 by these four compounds was analyzed using computational methods. Our aim was to see if the inhibition of caspase-1, an important biomolecule in the inflammatory response that triggers cytokine release, could shed light on how these drugs help to alleviate excessive cytokine production. We also measured the antioxidant activities of dexamethasone and colchicine when scavenging the superoxide radical using cyclic voltammetry methods. The experimental findings are associated with caspase-1 active site affinity towards these compounds. In evaluating our computational and experimental results, we here formulate a mechanism for caspase-1 inhibition by these drugs, which involves the active site amino acid Cys285 residue and is mediated by a transfer of protons, involving His237 and Ser339. It is proposed that the molecular moiety targeted by all of these drugs is a carbonyl group which establishes a S(Cys285)–C(carbonyl) covalent bond. [ABSTRACT FROM AUTHOR]

The outburst of inflammatory response and hypercoagulability are among the factors contributing to increased mortality in severe COVID-19 cases. Pentoxifylline (PTX), a xanthine-derived drug registered for the treatment of vascular claudication, has been reported to display broad-spectrum anti-inflammatory and immunomodulatory properties via adenosine A2A receptor (A2AR)-related mechanisms, in parallel to its rheological actions. Prior studies have indicated the efficacy of PTX in the treatment of various pulmonary diseases, including the management of acute respiratory distress syndrome of infectious causes. Therefore, PTX has been proposed to have potential benefits in the treatment of SARS-CoV-2 symptoms, as well as its complications. The aim of this review is to discuss available knowledge regarding the role of PTX as a complementary therapeutic in SARS-CoV-2. [ABSTRACT FROM AUTHOR]