Tranexamic Acid and Plasminogen/Plasmin Glaring Paradox in COVID-19.

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.

Cholinergic dysfunction in COVID-19: frantic search and hoping for the best.

A novel coronavirus known as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a potential cause of acute respiratory infection called coronavirus disease 2019 (COVID-19). The binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2) induces a series of inflammatory cellular events with cytopathic effects leading to cell injury and hyperinflammation. Severe SARS-CoV-2 infection may lead to dysautonomia and sympathetic storm due to dysfunction of the autonomic nervous system (ANS). Therefore, this review aimed to elucidate the critical role of the cholinergic system (CS) in SARS-CoV-2 infection. The CS forms a multi-faceted network performing diverse functions in the body due to its distribution in the neuronal and non-neuronal cells. Acetylcholine (ACh) acts on two main types of receptors which are nicotinic receptors (NRs) and muscarinic receptors (MRs). NRs induce T cell anergy with impairment of antigen-mediated signal transduction. Nicotine through activation of T cell NRs inhibits the expression and release of the pro-inflammatory cytokines. NRs play important anti-inflammatory effects while MRs promote inflammation by inducing the release of pro-inflammatory cytokines. SARS-CoV-2 infection can affect the morphological and functional stability of CS through the disruption of cholinergic receptors. SARS-CoV-2 spike protein is similar to neurotoxins, which can bind to nicotinic acetylcholine receptors (nAChR) in the ANS and brain. Therefore, cholinergic receptors mainly nAChR and related cholinergic agonists may affect the pathogenesis of SARS-CoV-2 infection. Cholinergic dysfunction in COVID-19 is due to dysregulation of nAChR by SARS-CoV-2 promoting the central sympathetic drive with the development of the sympathetic storm. As well, nAChR activators through interaction with diverse signaling pathways can reduce the risk of inflammatory disorders in COVID-19. In addition, nAChR activators may mitigate endothelial dysfunction (ED), oxidative stress (OS), and associated coagulopathy in COVID-19. Similarly, nAChR activators may improve OS, inflammatory changes, and cytokine storm in COVID-19. Therefore, nAChR activators like varenicline in virtue of its anti-inflammatory and anti-oxidant effects with direct anti-SARS-CoV-2 effect could be effective in the management of COVID-19.

Selinexor and COVID-19: The Neglected Warden.

A novel severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) has been confirmed as the cause of the global pandemic coronavirus disease 2019 (COVID-19). Different repurposed drugs have been trialed and used in the management of COVID-19. One of these agents was the anti-cancer Selinexor (SXR). SXR is an anti-cancer drug that acts by inhibition of nuclear exportin-1 (XPO1), which inhibits transport of nuclear proteins from the nucleus to the cytoplasm, leading to the induction of cell-cycle arrest and apoptosis. XPO1 inhibitors had antiviral effects, mainly against respiratory syncytial virus (RSV) and influenza virus. SXR inhibits transport of SARS-CoV-2 nuclear proteins to the cytoplasm with further inhibition of SARS-CoV-2 proliferation. SXR has the ability to prevent the development of a cytokine storm in COVID-19 by inhibiting the release of pro-inflammatory cytokines with the augmentation release of anti-inflammatory cytokines. In conclusion, SARS-CoV-2 infection is linked with activation of XPO1, leading to the triggering of inflammatory reactions and oxidative stress. Inhibition of XPO1 by Selinexor (SXR), a selective inhibitor of nuclear export (SINE), can reduce the proliferation of SARS-CoV-2 and associated inflammatory disorders. Preclinical and clinical studies are warranted in this regard.

Heparanase is the possible link between monkeypox and Covid-19: robust candidature in the mystic and present perspective.

Heparanase (HPSE) is an endoglycosidase cleaves heparan sulfate (HS) and this contributes to the degradation and remodeling of the extracellular matrix. HS cleaved by HPSE induces activation of autophagy and formation of autophagosommes which facilitate binding of HPSE to the HS and subsequent release of growth factors. The interaction between HPSE and HS triggers releases of chemokines and cytokines which affect inflammatory response and cell signaling pathways with development of hyperinflammation, cytokine storm (CS) and coagulopathy. HPSE expression is induced by both SARS-CoV-2 and monkeypox virus (MPXV) leading to induction release of pro-inflammatory cytokines, endothelial dysfunction and thrombotic events. Co-infection of MPX with SARS-CoV-2 may occur as we facing many outbreaks of MPX cases during Covid-19 pandemic. Therefore, targeting of HPSE by specific inhibitors may reduce the risk of complications in both SARS-CoV-2 and MPXV infections. Taken together, HPSE could be a potential link between MPX with SARS-CoV-2 in Covid-19 era.

Dantrolene and ryanodine receptors in COVID-19: The daunting task and neglected warden.

Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca2+ release from stores in the sarcoplasmic reticulum. DTN is mainly used in the management of malignant hyperthermia. RyRs are highly expressed in immune cells and are involved in different viral infections, including severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), because Ca2+ is necessary for viral replication, maturation and release. DTN can inhibit the proliferation of SARS-CoV-2, indicating its potential role in reducing entry and pathogenesis of SARS-CoV-2. DTN may increase clearance of SARS-CoV-2 and promote coronavirus disease 2019 (COVID-19) recovery by shortening the period of infection. DTN inhibits N-methyl-D-aspartate (NMDA) mediated platelets aggregations and thrombosis. Therefore, DTN may inhibit thrombosis and coagulopathy in COVID-19 through suppression of platelet NMDA receptors. Moreover, DTN has a neuroprotective effect against SARS-CoV-2 infection-induced brain injury through modulation of NMDA receptors, which are involved in excitotoxicity, neuronal injury and the development of neuropsychiatric disorders. In conclusion, DTN by inhibiting RyRs may attenuate inflammatory disorders in SARS-CoV-2 infection and associated cardio-pulmonary complications. Therefore, DNT could be a promising drug therapy against COVID-19. Preclinical and clinical studies are warranted in this regards.

SARS-COV-2 infection and Parkinson's disease: Possible links and perspectives.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The hallmarks are the presence of Lewy bodies composed mainly of aggregated α-synuclein and immune activation and inflammation in the brain. The neurotropism of SARS-CoV-2 with induction of cytokine storm and neuroinflammation can contribute to the development of PD. Interestingly, overexpression of α-synuclein in PD patients may limit SARS-CoV-2 neuroinvasion and degeneration of dopaminergic neurons; however, on the other hand, this virus can speed up the α-synuclein aggregation. The review aims to discuss the potential link between COVID-19 and the risk of PD, highlighting the need for further studies to authenticate the potential association. We have also overviewed the influence of SARS-CoV-2 infection on the PD course and management. In this context, we presented the prospects for controlling the COVID-19 pandemic and related PD cases that, beyond global vaccination and novel anti-SARS-CoV-2 agents, may include the development of graphene-based nanoscale platforms offering antiviral and anti-amyloid strategies against PD.

Hemolytic anemia in COVID-19.

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.

Nitazoxanide and COVID-19: A review.

Coronavirus disease 2019 (COVID-19) is a current global illness triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) leading to acute viral pneumonia, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and cytokine storm in severe cases. In the COVID-19 era, different unexpected old drugs are repurposed to find out effective and cheap therapies against SARS-CoV-2. One of these elected drugs is nitazoxanide (NTZ) which is an anti-parasitic drug with potent antiviral activity. It is effectively used in the treatment of protozoa and various types of helminths in addition to various viral infections. Thus, we aimed to elucidate the probable effect of NTZ on SARS-CoV-2 infections. Findings of the present study illustrated that NTZ can reduce SARS-CoV-2-induced inflammatory reactions through activation of interferon (IFN), restoration of innate immunity, inhibition of the release of pro-inflammatory cytokines, suppression of the mammalian target of rapamycin (mTOR), and induction of autophagic cell death. Moreover, it can inhibit the induction of oxidative stress which causes cytokine storm and is associated with ALI, ARDS, and multi-organ damage (MOD). This study concluded that NTZ has important anti-inflammatory and immunological properties that may mitigate SARS-CoV-2 infection-induced inflammatory disorders. Despite broad-spectrum antiviral properties of NTZ, the direct anti-SARS-CoV-2 effect was not evident and documented in recent studies. Then, in silico and in vitro studies in addition to clinical trials and prospective studies are needed to confirm the beneficial impact of NTZ on the pathogenesis of SARS-CoV-2 infection.

Receptor-dependent effects of sphingosine-1-phosphate (S1P) in COVID-19: the black side of the moon.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection leads to hyper-inflammation and amplified immune response in severe cases that may progress to cytokine storm and multi-organ injuries like acute respiratory distress syndrome and acute lung injury. In addition to pro-inflammatory cytokines, different mediators are involved in SARS-CoV-2 pathogenesis and infection, such as sphingosine-1-phosphate (S1P). S1P is a bioactive lipid found at a high level in plasma, and it is synthesized from sphingomyelin by the action of sphingosine kinase. It is involved in inflammation, immunity, angiogenesis, vascular permeability, and lymphocyte trafficking through G-protein coupled S1P receptors. Reduction of the circulating S1P level correlates with COVID-19 severity. S1P binding to sphingosine-1-phosphate receptor 1 (S1PR1) elicits endothelial protection and anti-inflammatory effects during SARS-CoV-2 infection, by limiting excessive INF-α response and hindering mitogen-activated protein kinase and nuclear factor kappa B action. However, binding to S1PR2 opposes the effect of S1PR1 with vascular inflammation, endothelial permeability, and dysfunction as the concomitant outcome. This binding also promotes nod-like receptor pyrin 3 (NLRP3) inflammasome activation, causing liver inflammation and fibrogenesis. Thus, higher expression of macrophage S1PR2 contributes to the activation of the NLRP3 inflammasome and the release of pro-inflammatory cytokines. In conclusion, S1PR1 agonists and S1PR2 antagonists might effectively manage COVID-19 and its severe effects. Further studies are recommended to elucidate the potential conflict in the effects of S1P in COVID-19.

A perspective study of the possible impact of obeticholic acid against SARS-CoV-2 infection.

The causative agent of CoV disease 2019 is a new coronavirus CoV type 2, affecting the respiratory tract with severe manifestations (SARS-CoV-2). Covid-19 is mainly symptomless, with slight indications in about 85% of the affected cases. Many efforts were done to face this pandemic by testing different drugs and agents to make treatment protocols in different countries. However, the use of these proposed drugs is associated with the development of adverse events. Remarkably, the successive development of SARS-CoV-2 variants which could affect persons even they were vaccinated, prerequisite wide search to find efficient and safe agents to face SARS-CoV-2 infection. Obeticholic acid (OCA), which has anti-inflammatory effects, may efficiently treat Covid-19. Thus, the goal of this perspective study is to focus on the possible medicinal effectiveness in managing Covid-19. OCA is a powerful farnesoid X receptor (FXR) agonist possessing marked antiviral and anti-inflammatory effects. FXR is dysregulated in Covid-19 resulting in hyper-inflammation with concurrent occurrence of hypercytokinemia. Interestingly, OCA inhibits the reaction between this virus and angiotensin-converting enzyme type 2 (ACE2) receptors. FXR agonists control the expression of ACE2 and the inflammatory signaling pathways in this respiratory syndrome, which weakens the effects of Covid-19 disease and accompanied complications. Taken together, FXR agonists like OCA may reveal both direct and indirect impacts in the modulation of immune reaction in SARS-CoV-2 conditions. It is highly recommended to perform many investigations regarding different phases of the discovery of new drugs.

Targeting of neuroinflammation by glibenclamide in Covid-19: old weapon from arsenal.

In coronavirus disease 2019 (Covid-19) era, neuroinflammation may develop due to neuronal tropism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or associated immune activation, cytokine storm, and psychological stress. SARS-CoV-2 infection and linked cytokine storm may cause blood-brain barrier (BBB) injury through which activated immune cells and SARS-CoV-2 can pass into the brain causing activation of glial cells with subsequent neuroinflammation. Different therapeutic regimens were suggested to alleviate Covid-19-induced neuroinflammation. Since glibenclamide has anti-inflammatory and neuroprotective effects, it could be effective in mitigation of SARS-CoV-2 infection-induced neuroinflammation. Glibenclamide is a second-generation drug from the sulfonylurea family, which acts by inhibiting the adenosine triphosphate (ATP)-sensitive K channel in the regulatory subunit of type 1 sulfonylurea receptor (SUR-1) in pancreatic ß cells. Glibenclamide reduces neuroinflammation and associated BBB injury by inhibiting the nod-like receptor pyrin 3 (NLRP3) inflammasome, oxidative stress, and microglial activation. Therefore, glibenclamide through inhibition of NLRP3 inflammasome, microglial activation, and oxidative stress may attenuate SARS-CoV-2-mediated neuroinflammation.

The potential link between Covid-19 and multiple myeloma: A new saga.

BACKGROUND: Covid-19 is considered a primary respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury and acute respiratory distress syndrome (ARDS). In addition, though, extra-pulmonary manifestations of Covid-19 have been shown. Furthermore, severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) infection may coexist with several malignancies, including multiple myeloma (MM). METHODS: This critical literature review aimed to find the potential association between SARS-CoV-2 infection and MM in Covid-19 patients with underlying MM. Narrative literature and databases search revealed that ARDS is developed in both MM and Covid-19 due to hypercalcemia and proteasome dysfunction. RESULTS: Notably, the expression of angiogenic factors and glutamine deficiency could link Covid-19 severity and MM in the pathogenesis of cardiovascular complications. MM and Covid-19 share thrombosis as a typical complication; unlike thrombosis in Covid-19, which reflects disease severity, thrombosis does not reflect disease severity in MM. In both conditions, thromboprophylaxis is essential to prevent pulmonary thrombosis and other thromboembolic disorders. Moreover, Covid-19 may exacerbate the development of acute kidney injury and neurological complications in MM patients. CONCLUSION: These findings highlighted that MM patients might be a risk group for Covid-19 severity due to underlying immunosuppression and most of those patients need specific management in the Covid-19 era.

Favipiravir in SARS-CoV-2 Infection: Is it Worth it?

Favipiravir is a potential antiviral drug undergoing clinical trials to manage various viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Favipiravir possesses antiviral properties against RNA viruses, including SARS-CoV-2. Unfortunately, these viruses do not have authorized antiviral drugs for the management of diseases resulting from their infection, hence the dire need to accentuate the discovery of antiviral drugs that are efficacious and have a broad spectrum. Favipiravir acts primarily by blocking inward and outward movements of the virus from cells. Favipiravir is a prodrug undergoing intracellular phosphorylation and ribosylation to form an active form, favipiravir-RTP, which binds viral RNA-dependent RNA polymerase (RdRp). Considering the novel mechanism of favipiravir action, especially in managing viral infections, it is vital to pay more attention to the promised favipiravir hold in the management of SARS-CoV-2, its efficacy, and dosage regimen, and interactions with other drugs. In conclusion, favipiravir possesses antiviral properties against RNA viruses, including COVID- 19. Favipiravir is effective against SARS-CoV-2 infection through inhibition of RdRp. Pre-clinical and large-scalp prospective studies are recommended for efficacy and long-term safety of favipiravir in COVID-19.

The potential molecular implications of adiponectin in the evolution of SARS-CoV-2: Inbuilt tendency.

Adiponectin (APN) is an adipokine concerned in the regulation of glucose metabolism, insulin sensitivity and fatty acid oxidation. APN plays a critical role in viral infections by regulating the immune response through its anti-inflammatory/pro-inflammatory axis. Reduction of APN may augment the severity of viral infections because APN inhibits immune cells' response via suppression of inflammatory signaling pathways and stimulation of adenosine monophosphate protein kinase (AMPK). Moreover, APN inhibits the stimulation of nuclear factor kappa B (NF-κB) and regulates the release of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukins (IL-18, IL-6). In COVID-19, abnormalities of the fatty tissue due to oxidative stress (OS) and hyperinflammation may inhibit the production and release of APN. APN has lung-protective effect and can prevent SARS-CoV-2-induced acute lung injury (ALI) through the amelioration of endoplasmic reticulum (ER) stress, endothelial dysfunction (ED) and stimulation of peroxisome proliferator-activated receptor-alpha (PPAR-α). It has been established that there is a potential correlation between inflammatory signal transduction pathways and APN that contributes to the development of SARS-CoV-2 infections. Deregulation of these molecular pathways affects the expression of APN and vice versa. In addition, the reduction of APN effect in SARS-CoV-2 infection could be a potential cause of the exacerbation of pro-inflammatory effects which are associated with the disease severity. In this context, exploratory, developmental, and extensive prospective studies are necessary.

Potential Therapeutic Benefits of Metformin Alone and in Combination with Sitagliptin in the Management of Type 2 Diabetes Patients with COVID-19.

Type 2 diabetes mellitus (T2DM) is a potential risk factor for the development of COVID-19 and is associated with higher severity and mortality rates. T2DM patients are commonly treated with metformin monotherapy or metformin plus sitagliptin. In the present case-control, single-center cohort study, a total number of 112 T2DM patients suffering from COVID-19 and aged 44-62 years old were compared with 78 T2DM patients without COVID-19 and aged 42-56 years old. Both the patient group and the control group were allocated into four groups. Group A: T2DM patients with COVID-19 on metformin treatments plus standard therapy (n = 60); group B: T2DM patients with COVID-19 on metformin plus sitagliptin plus standard therapy (n = 52); group C: T2DM patients without COVID-19 on metformin treatments (n = 40); and group D: T2DM patients without COVID-19 on metformin plus sitagliptin (n = 38). The investigation duration was 2-3 weeks. Anthropometric measurements, serological and biochemical investigations, pulmonary radiological findings, and clinical outcomes were evaluated. Only 101 T2DM patients with COVID-19 continued the study, 71 (70.29%) with mild-moderate COVID-19 and 30 (29.7%) with severe COVID-19 were compared with 78 T2DM patients as a control. Inflammatory biomarkers (C reactive protein, ferritin, and procalcitonin), a lung injury biomarker (lactate dehydrogenase), and a coagulopathy biomarker (D-dimer) were elevated in severe COVID-19 patients compared with mild-moderate COVID-19 (p < 0.05) and T2DM patients (p < 0.05). However, metformin plus sitagliptin was more effective than metformin monotherapy in T2DM patients with COVID-19, as evidenced by the mitigation of oxidative stress, CT scan score, and clinical outcomes. The present study confirmed the protective effects of this combination against the development of COVID-19 severity, as most T2DM COVID-19 patients develop mild-moderate forms. Herein, the combination of metformin and sitagliptin may lead to more beneficial effects than metformin monotherapy.

Central Effects of Ivermectin in Alleviation of Covid-19-induced Dysauto-nomia.

Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immunoinflammatory 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, 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. Ivermectin (IVM) is a robust repurposed drug 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 managing Covid-19-induced dysautonomia.

Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail.

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.

Common NLRP3 inflammasome inhibitors and Covid-19: Divide and conquer.

Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm, and hypercytokinemia due to activation of the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the stimulation and synthesis of natural killer cells (NKs), NFκB, and interferon-gamma (INF-γ), while inhibiting IL-33 expression. Various efforts have identified selective inhibitors of NLRP3 inflammasome. To achieve this, studies are exploring the screening of natural compounds and/or repurposing of clinical drugs to identify potential NLRP3 inhibitors. NLRP3 inflammasome inhibitors are expected to suppress exaggerated immune reaction and cytokine storm-induced-organ damage in SARS-CoV-2 infection. Therefore, NLRP3 inflammasome inhibitors could mitigate the immune-overreaction and hypercytokinemia in Covid-19 infection.