The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies

Zhao, Ni; Di, Bin; Xu, Lili

doi:10.1016/j.cytogfr.2021.06.002

Cited by 115 publications

(116 citation statements)

References 142 publications

(199 reference statements)

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“…Likewise, bile acids are endogenous inhibitors of the NLRP3 inflammasome via NLRP3 ubiquitination, through the TGR5-cAMP-PKA axis. Bile acids could act through this pathway and regulate the activation of the NLRP3 inflammasome 56 and attenuate COVID-19 57 . Furthermore, it has been reported that UDCA presents anti-apoptotic activity by modulating mitochondrial membrane permeability transition 58 .…”

Section: Discussionmentioning

confidence: 99%

Interaction of Spike protein and lipid membrane of SARS-CoV-2 with Ursodeoxycholic acid, an in-silico analysis

Canales

Mayoral

Hernández-Huerta

et al. 2021

Sci Rep

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Numerous repositioned drugs have been sought to decrease the severity of SARS-CoV-2 infection. It is known that among its physicochemical properties, Ursodeoxycholic Acid (UDCA) has a reduction in surface tension and cholesterol solubilization, it has also been used to treat cholesterol gallstones and viral hepatitis. In this study, molecular docking was performed with the SARS-CoV-2 Spike protein and UDCA. In order to confirm this interaction, we used Molecular Dynamics (MD) in “SARS-CoV-2 Spike protein-UDCA”. Using another system, we also simulated MD with six UDCA residues around the Spike protein at random, naming this “SARS-CoV-2 Spike protein-6UDCA”. Finally, we evaluated the possible interaction between UDCA and different types of membranes, considering the possible membrane conformation of SARS-CoV-2, this was named “SARS-CoV-2 membrane-UDCA”. In the “SARS-CoV-2 Spike protein-UDCA”, we found that UDCA exhibits affinity towards the central region of the Spike protein structure of − 386.35 kcal/mol, in a region with 3 alpha helices, which comprises residues from K986 to C1032 of each monomer. MD confirmed that UDCA remains attached and occasionally forms hydrogen bonds with residues R995 and T998. In the presence of UDCA, we observed that the distances between residues atoms OG1 and CG2 of T998 in the monomers A, B, and C in the prefusion state do not change and remain at 5.93 ± 0.62 and 7.78 ± 0.51 Å, respectively, compared to the post-fusion state. Next, in “SARS-CoV-2 Spike protein-6UDCA”, the three UDCA showed affinity towards different regions of the Spike protein, but only one of them remained bound to the region between the region's heptad repeat 1 and heptad repeat 2 (HR1 and HR2) for 375 ps of the trajectory. The RMSD of monomer C was the smallest of the three monomers with a value of 2.89 ± 0.32, likewise, the smallest RMSF was also of the monomer C (2.25 ± 056). In addition, in the simulation of “SARS-CoV-2 membrane-UDCA”, UDCA had a higher affinity toward the virion-like membrane; where three of the four residues remained attached once they were close (5 Å, to the centre of mass) to the membrane by 30 ns. However, only one of them remained attached to the plasma-like membrane and this was in a cluster of cholesterol molecules. We have shown that UDCA interacts in two distinct regions of Spike protein sequences. In addition, UDCA tends to stay bound to the membrane, which could potentially reduce the internalization of SARS-CoV-2 in the host cell.

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Section: Discussionmentioning

confidence: 99%

Interaction of Spike protein and lipid membrane of SARS-CoV-2 with Ursodeoxycholic acid, an in-silico analysis

Canales

Mayoral

Hernández-Huerta

et al. 2021

Sci Rep

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“…NLRP3-stimulation has been shown to intensely induce cytokine expression during the cytokine storm in COVID-19 and periodontitis [ 20 ]. SARS-CoV-2 might directly activate NLRP3 inflammasome, and dysregulated NLRP3 inflammasome activity has been attributed with severe forms of COVID-19 with tissue damage and relevant cytokine storm [ 26 , 27 ]. Potential therapies targeting inflammasomes have been recently introduced for the treatment of COVID-19 and periodontitis.…”

Section: Immunologic Links Between Covid-19 and Periodontitismentioning

confidence: 99%

COVID-19 Pandemic and Periodontal Practice: The Immunological, Clinical, and Economic Points of View

Darestani

Akbari

Yaghobee

et al. 2022

BioMed Research International

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The recent global health problem, COVID-19, has had far-reaching impacts on lifestyles. Although many effective WHO-approved vaccines have been produced that have reduced the spread and severity of the disease, it appears to persist in humans for a long time and possibly forever as everyday it turns out to have new mutations. COVID-19 involves the lungs and other organs primarily through cytokine storms, which have been implicated in many other inflammatory disorders, including periodontal diseases. COVID-19 is in a close association with dental and periodontal practice from two respects: first, repeated mandatory lockdowns have reduced patient referrals to dentists and limited the dental and periodontal procedures to emergency treatments, whereas it is important to recognize the oral manifestations of COVID-19 as well as the influence of oral and periodontal disease on the severity of COVID-19. Second, dentistry is one of the high-risk professions in terms of close contact with unmasked individuals, necessitating redefining the principles of infection control. The pressures of the economic recession on patients as well as dentists add to the difficulty of resuming elective dental services. Therefore, this study is divided into two parts corresponding to what mentioned above: the first part examines the clinical and immunological associations between COVID-19 and periodontal and oral diseases, and the second part delineates the measures needed to control the disease transmission in dental clinics as well as the economic impact of the pandemic era on dental services.

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“…Activation of immune system during viral infections is highly correlated with NLRP3 (Nod-like receptor family, pyrin domain-containing 3) inflammasome [111] , [112] , [113] . There are numerous literatures linking NLRP3 inflammasome and cytokine storm in the pathogenesis of COVID-19 patients [114] . The viral (SARS-CoV 3a) protein triggers the activation of NLP3 inflammasome in the lipopolysaccharide-primed macrophages and stimulates IL-1β secretion which leads to K + efflux and generation of mitochondrial reactive oxygen species [115] .…”

Section: Emerging Molecular Drug Targets For Covid-19associated Ardsmentioning

confidence: 99%

COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends

Thapa

Verma

Singh

et al. 2021

International Immunopharmacology

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The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies

Abstract: Graphical abstract

Cited by 115 publications

References 142 publications

Interaction of Spike protein and lipid membrane of SARS-CoV-2 with Ursodeoxycholic acid, an in-silico analysis

Interaction of Spike protein and lipid membrane of SARS-CoV-2 with Ursodeoxycholic acid, an in-silico analysis

COVID-19 Pandemic and Periodontal Practice: The Immunological, Clinical, and Economic Points of View

COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends

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