Tocilizumab in SARS-CoV-2 Patients with the Syndrome of Cytokine Storm: A Narrative Review

Kulanthaivel, Shanmugaraj

doi:10.2174/18761038mta55otgh5

Cited by 9 publications

(2 citation statements)

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“…The SARS-CoV-2 pandemic represented the third zoonotic introduction of a coronavirus into humans, preceded by the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) epidemics [ 8 , 9 ]. COVID-19 is responsible for a multisystem disease characterized by the presence of a cytokine storm [ 10 , 11 , 12 , 13 ]. During COVID-19, the generalized inflammatory state determines a multi-organ involvement with a synergistic effect in the development of the damage connected to the disease.…”

Section: Introductionmentioning

confidence: 99%

Liver Damage and Impaired Coagulation in COVID-19 Patients: A Case Series

Abenavoli,

Aquila,

Sacco

et al. 2023

Diseases

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the scientific community wonders if liver injury in patients suffering from severe forms is a direct consequence of the virus or secondary manifestations of systemic inflammation. The liver plays an essential role in the development of the inflammatory storm typical of this disease, and its involvement is associated with worse clinical outcomes and a higher risk of morbidity and mortality from Coronavirus disease 2019 (COVID-19). Methods: Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes. Results: The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material. Conclusions: Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.

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Section: Introductionmentioning

confidence: 99%

Liver Damage and Impaired Coagulation in COVID-19 Patients: A Case Series

Abenavoli,

Aquila,

Sacco

et al. 2023

Diseases

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“…These antivirals inhibit SARS-CoV-2 enzymes, such as the SARS-CoV-2 polymerase or protease, or inhibit SARS-CoV-2 viral entry into host cells. Inhibitors such as remdesivir, tocilizumab, and baricitinib are FDA approved (Kalil et al, 2021;Kulanthaivel et al, 2021). Previously developed vaccines and antivirals are extremely effective in reducing hospitalizations and deaths among vaccinated individuals (Shang et al, 2020;Tenforde et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Exploring the disruption of SARS-CoV-2 RBD binding to hACE2

Carter,

Airas,

Gladden

et al. 2023

Front. Chem.

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The COVID-19 pandemic was declared due to the spread of the novel coronavirus, SARS-CoV-2. Viral infection is caused by the interaction between the SARS-CoV-2 receptor binding domain (RBD) and the human ACE2 receptor (hACE2). Previous computational studies have identified repurposed small molecules that target the RBD, but very few have screened drugs in the RBD–hACE2 interface. When studies focus solely on the binding affinity between the drug and the RBD, they ignore the effect of hACE2, resulting in an incomplete analysis. We screened ACE inhibitors and previously identified SARS-CoV-2 inhibitors for binding to the RBD—hACE2 interface, and then conducted 500 ns of unrestrained molecular dynamics (MD) simulations of fosinopril, fosinoprilat, lisinopril, emodin, diquafosol, and physcion bound to the interface to assess the binding characteristics of these ligands. Based on MM-GBSA analysis, all six ligands bind favorably in the interface and inhibit the RBD–hACE2 interaction. However, when we repeat our simulation by first binding the drug to the RBD before interacting with hACE2, we find that fosinopril, fosinoprilat, and lisinopril result in a strongly interacting trimeric complex (RBD-drug-hACE2). Hydrogen bonding and pairwise decomposition analyses further suggest that fosinopril is the best RBD inhibitor. However, when lisinopril is bound, it stabilizes the trimeric complex and, therefore, is not an ideal potential drug candidate. Overall, these results reveal important atomistic interactions critical to the binding of the RBD to hACE2 and highlight the significance of including all protein partners in the evaluation of a potential drug candidate.

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In silico drug repurposing in COVID-19: A network-based analysis

Sibilio¹,

Bini²,

Fiscon³

et al. 2021

Biomedicine & Pharmacotherapy

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The SARS-CoV-2 pandemic is a worldwide public health emergency. Despite the beginning of a vaccination campaign, the search for new drugs to appropriately treat COVID-19 patients remains a priority. Drug repurposing represents a faster and cheaper method than de novo drug discovery. In this study, we examined three different network-based approaches to identify potentially repurposable drugs to treat COVID-19. We analyzed transcriptomic data from whole blood cells of patients with COVID-19 and 21 other related conditions, as compared with those of healthy subjects. In addition to conventionally used drugs (e.g., anticoagulants, antihistaminics, anti-TNFα antibodies, corticosteroids), unconventional candidate compounds, such as SCN5A inhibitors and drugs active in the central nervous system, were identified. Clinical judgment and validation through clinical trials are always mandatory before use of the identified drugs in a clinical setting.

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Tocilizumab in SARS-CoV-2 Patients with the Syndrome of Cytokine Storm: A Narrative Review

Cited by 9 publications

References 0 publications

Liver Damage and Impaired Coagulation in COVID-19 Patients: A Case Series

Liver Damage and Impaired Coagulation in COVID-19 Patients: A Case Series

Exploring the disruption of SARS-CoV-2 RBD binding to hACE2

In silico drug repurposing in COVID-19: A network-based analysis

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