COVID-19 and liver injury in individuals with obesity.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.

Cordycepin as a Promising Inhibitor of SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp).

BACKGROUND: SARS-CoV-2, which emerged in Wuhan, China, is a new global threat that has killed millions of people and continues to do so. This pandemic has not only threatened human life but has also triggered economic downturns across the world. Researchers have made significant strides in discovering molecular insights into SARSCoV- 2 pathogenesis and developing vaccines, but there is still no successful cure for SARS-CoV-2 infected patients. OBJECTIVE: The present study has proposed a drug-repositioning pipeline for the design and discovery of an effective fungal-derived bioactive metabolite as a drug candidate against SARS-CoV-2. METHODS: Fungal derivative "Cordycepin" was selected for this study to investigate the inhibitory properties against RNA-dependent RNA polymerase (RdRp) (PDB ID: 6M71) of SARS-CoV-2. The pharmacological profile, intermolecular interactions, binding energy, and stability of the compound were determined utilizing cheminformatic approaches. Subsequently, molecular dynamic simulation was performed to better understand the binding mechanism of cordycepin to RdRp. RESULTS: The pharmacological data and retrieved molecular dynamics simulations trajectories suggest excellent drug-likeliness and greater structural stability of cordycepin, while the catalytic residues (Asp760, Asp761), as well as other active site residues (Trp617, Asp618, Tyr619, Trp800, Glu811) of RdRp, showed better stability during the overall simulation span. CONCLUSION: Promising results of pharmacological investigation along with molecular simulations revealed that cordycepin exhibited strong inhibitory potential against SARSCoV- 2 polymerase enzyme (RdRp). Hence, cordycepin should be highly recommended to test in a laboratory to confirm its inhibitory potential against the SARS-CoV-2 polymerase enzyme (RdRp).