Role of comorbidities like diabetes on severe acute respiratory syndrome coronavirus-2: A review.

Pandemic coronavirus disease-2019, commonly known as COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious disease with a high mortality rate. Various comorbidities and their associated symptoms accompany SARS-CoV-2 infection. Among the various comorbidities like hypertension, cardiovascular disease and chronic obstructive pulmonary disease, diabetes considered as one of the critical comorbidity, which could affect the survival of infected patients. The severity of COVID-19 disease intensifies in patients with elevated glucose level probably via amplified pro-inflammatory cytokine response, poor innate immunity and downregulated angiotensin-converting enzyme 2. Thus, the use of ACE inhibitors or angiotensin receptor blockers could worsen the glucose level in patients suffering from novel coronavirus infection. It also observed that the direct ß-cell damage caused by virus, hypokalemia and cytokine and fetuin-A mediated increase in insulin resistance could also deteriorate the diabetic condition in COVID-19 patients. This review highlights the current scenario of coronavirus disease in pre-existing diabetic patients, epidemiology, molecular perception, investigations, treatment and management of COVID-19 disease in patients with pre-existing diabetes. Along with this, we have also discussed unexplored therapies and future perspectives for coronavirus infection.

Structure-based identification of small molecules against influenza A virus endonuclease: an in silico and in vitro approach.

Influenza viruses are known to cause acute respiratory illness, sometimes leading to high mortality rates. Though there are approved influenza antivirals available, their efficacy has reduced over time, due to the drug resistance crisis. There is a perpetual need for newer and better drugs. Drug screening based on the interaction dynamics with different viral target proteins has been a preferred approach in the antiviral drug discovery process. In this study, the FDA approved drug database was virtually screened with the help of Schrödinger software, to select small molecules exhibiting best interactions with the influenza A virus endonuclease protein. A detailed cytotoxicity profiling was carried out for the two selected compounds, cefepime and dolutegravir, followed by in vitro anti-influenza screening using plaque reduction assay. Cefepime showed no cytotoxicity up to 200 µM, while dolutegravir was non-toxic up to 100 µM in Madin-Darby canine kidney cells. The compounds did not show any reduction in viral plaque numbers indicating no anti-influenza activity. An inefficiency in the translation of the molecular interactions into antiviral activity does not necessarily mean that the molecules were inactive. Nevertheless, testing the molecules for endonuclease inhibition per se can be considered a worthwhile approach.