ABSTRACT
Coronavirus disease 2019 (COVID-19) has been reported to affect nearly all body systems. Kidney affection has been observed in several studies. The effect of COVID-19 on renal function is beyond that occurring in pneumonia or severe respiratory distress cases. Renal affection is attributed to several factors, including the mechanism of viral injury. Patients with preexisting kidney injury are at increased risk of infection. Early detection and management are crucial to avoid morbidity and mortality, prevent the spread and contamination of hemodialysis Units. Early detection and treatment of kidney involvement in COVID-19 are vital to avoid increased morbidity and mortality. Proper selection of drugs and fluid management is vital in cases with kidney involvement. This review aims to discuss the clinical and pathophysiological affection of the kidney in COVID-19.
ABSTRACT
The coronavirus helicase is an essential enzyme required for viral replication/transcription pathways. Structural studies revealed a sulphate moiety that interacts with key residues within the nucleotide-binding site of the helicase. Compounds with a sulphoxide or a sulphone moiety could interfere with these interactions and consequently inhibit the enzyme. The molecular operating environment (MOE) was used to dock 189 sulphoxide and sulphone-containing FDA-approved compounds to the nucleotide-binding site. Zafirlukast, a leukotriene receptor antagonist used to treat chronic asthma, achieved the lowest docking score at -8.75 kcals/mol. The inhibitory effect of the compounds on the SARS-CoV-2 helicase dsDNA unwinding activity was tested by a FRET-based assay. Zafirlukast was the only compound to inhibit the enzyme (IC50 = 16.3 µM). The treatment of Vero E6 cells with 25 µM zafirlukast prior to SARS-CoV-2 infection decreased the cytopathic effects of SARS-CoV-2 significantly. These results suggest that zafirlukast alleviates SARS-CoV-2 pathogenicity by inhibiting the viral helicase and impairing the viral replication/transcription pathway. Zafirlukast could be clinically developed as a new antiviral treatment for SARS-CoV-2 and other coronavirus diseases. This discovery is based on molecular modelling, in vitro inhibition of the SARS-CoV helicase activity and cell-based SARS-CoV-2 viral replication.
Subject(s)
Antiviral Agents/pharmacology , DNA Helicases/antagonists & inhibitors , Indoles/pharmacology , Phenylcarbamates/pharmacology , SARS-CoV-2/drug effects , Sulfonamides/pharmacology , Animals , Chlorocebus aethiops , Fluorescence Resonance Energy Transfer , Quantitative Structure-Activity Relationship , SARS-CoV-2/enzymology , Vero Cells , Virus Replication/drug effects , COVID-19 Drug TreatmentABSTRACT
Objectives: The pandemic of coronavirus disease 2019 (COVID-19) has been one of the major health concerns for all the countries around the globe. This study was aimed to study the potential effect of COVID-19 virus on the level of blood ghrelin appetite hormone in order to determine the influence of this infection on the patient appetite. Methods: This is a cross-sectional study was conducted between July and the end of August 2020 in the western region of Saudi Arabia. A total of 50 confirmed positive patients with COVID-19 (positive group) and 30 control healthy subjects with negative blood samples (negative group) were collected to determine the level of ghrelin appetite hormone using the human ghrelin (GHRL) ELISA technique. A student's t-test was carried out to find out the statistical change between different study groups. Results: The serum total ghrelin concentrations, on average, were 51.32 pg/mL on positive group and 50.37 pg/mL on negative group, respectively. The difference of ghrelin was statistically insignificant between the two groups (P >0.05). Although the sample size of the study was small, the results showed high number of COVID-19 cases in male than female. Conclusion: The current data shows that there are no significant changes in the level of serum ghrelin hormone in COVID-19 patients. Consequently, it might be possible that the ghrelin hormone showed potential changes in the saliva compared to the effect in the blood. Thus, a further analysis of the ghrelin hormone in the saliva of COVID-19 patients will be conducted in the near future.