Remdesivir in Coronavirus Disease 2019 (COVID-19) treatment: a review of evidence.

COVID-19 is an infectious disease caused by a novel ß-coronavirus, belonging to the same subgenus as the Severe Acute Respiratory Syndrome (SARS) virus. Remdesivir, an investigational broad-spectrum antiviral agent has previously demonstrated in vitro activity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and in vivo efficacy against other related coronaviruses in animal models. Its safety profile has been tested in a compassionate use setting for patients with COVID-19. The current therapeutic studies demonstrate clinical effectiveness of remdesivir in COVID-19 patients by shortening time to clinical recovery, and hospital stay. In this review, we critically analyze the current evidence of remdesivir against COVID-19 and dissect the aspects over its safety and efficacy. Based on existing data, remdesivir can be regarded as a potential therapeutic agent against COVID-19. Further large-scale, randomized placebo-controlled clinical trials are, however, awaited to validate these findings.

Are Adequate Vitamin D Levels Helpful in Fighting COVID-19? A Look at the Evidence.

COVID-19 is a global pandemic with high mortality in vulnerable groups. Given the current lack of definitive treatment or vaccine that significantly reduces mortality rate, governments, researchers and healthcare providers are racing to find possible solutions to the crisis. Vitamin D and its analogues have been previously studied for their non-skeletal benefits. In particular, questions regarding their role in the modulation of immunity have re-surfaced, in view of possible epidemiological links observed between COVID-19 and vitamin D levels in selected populations. In this review, we highlight potential mechanisms and summarise the evidence for and against the potential role of vitamin D supplementation in our fight against COVID-19.

Co-regulation of cell polarization and migration by caveolar proteins PTRF/Cavin-1 and caveolin-1.

Caveolin-1 and caveolae are differentially polarized in migrating cells in various models, and caveolin-1 expression has been shown to quantitatively modulate cell migration. PTRF/cavin-1 is a cytoplasmic protein now established to be also necessary for caveola formation. Here we tested the effect of PTRF expression on cell migration. Using fluorescence imaging, quantitative proteomics, and cell migration assays we show that PTRF/cavin-1 modulates cellular polarization, and the subcellular localization of Rac1 and caveolin-1 in migrating cells as well as PKCα caveola recruitment. PTRF/cavin-1 quantitatively reduced cell migration, and induced mesenchymal epithelial reversion. Similar to caveolin-1, the polarization of PTRF/cavin-1 was dependent on the migration mode. By selectively manipulating PTRF/cavin-1 and caveolin-1 expression (and therefore caveola formation) in multiple cell systems, we unveil caveola-independent functions for both proteins in cell migration.

PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9.

Caveolae are specialized plasma membrane subdomains with a distinct lipid and protein composition, which play an essential role in cell physiology by performing trafficking and signalling functions. The structure and functions of caveolae have been shown to require caveolin-1, a major protein component of caveolae. Caveolin-1 expression and secretion are increased in metastatic prostate cancer, and caveolin-1 seems to contribute to prostate cancer growth and metastasis. Recently, a cytoplasmic protein named PTRF (Polymerase I and Transcript Release Factor) or cavin-1 was found to be required, in concert with caveolin-1, for the formation and functions of caveolae. Genetic ablation of PTRF results in loss of caveolae while caveolin-1 is still expressed, albeit at reduced level, but associates with flat plasma membrane. In metastatic PC3 prostate cancer cells that express abundant caveolin-1 but no PTRF, heterologous PTRF expression restores caveola formation and caveolin-1 distribution (Hill et al., 2008; Cell 132, 113-124). We now show that PTRF/cavin-1-expressing PC3 cells exhibit decreased migration, and that this effect is mediated by reduced MMP9 production. PTRF/cavin-1, and to a lesser extent, cavin-2, -3, and -4 all decreased MMP9. We further show that the PTRF/cavin-1-mediated reduction of MMP9 production is independent of caveola formation. Taken together, our results suggest that PTRF/cavin-1 expression alters prostate cancer aggressiveness.

Mango extracts and the mango component mangiferin promote endothelial cell migration.

This study tested the hypothesis that mango extracts contain bioactive molecules capable of modulating endothelial cell migration, an essential step in the formation of new blood vessels or angiogenesis. The formation of new blood vessels is an important therapeutic target for diseases such as limb ischemia, coronary infarction or stroke. We examined the effect of mango peel and flesh extracts as well as the individual polyphenolic molecules, mangiferin and quercetin, on bovine aortic cell migration using a modified Boyden chamber assay. Our results show that mangiferin, and extracts rich in mangiferin, increase endothelial cell migration. The dose-effect relationship for various extracts further suggests that this action of mangiferin is modulated by other components present in the extracts. The promigratory effect of mango extracts or mangiferin was unrelated to an effect on cell proliferation, and did not involve a change in the production of matrix metalloprotease-2 or -9 by the endothelial cells. Taken together, these results suggest that mangiferin present in mango extracts may have health promoting effects in diseases related to the impaired formation of new blood vessels.