siRNA Therapeutics for the Therapy of COVID-19 and Other Coronaviruses.

The ongoing pandemic of global concern has killed about three million humans and affected around 151 million people worldwide, as of April 30, 2021. Although recently approved vaccines for COVID-19 are engendering hope, finding new ways to cure the viral pandemic is still a quest for researchers worldwide. Major pandemics in history have been of viral origin, such as SARS, MERS, H1NI, Spanish flu, and so on. A larger emphasis has been on discovering potential vaccines, novel antiviral drugs, and agents that can mitigate the viral infection symptoms; however, a relatively new area, RNA interference (RNAi), has proven effective as an antiviral agent. The RNAi phenomenon has been largely exploited to cure cancer, neurodegenerative diseases, and some rare diseases. The U.S. Food and Drug Administration has recently approved three siRNA products for human use that garner significant hope in siRNA therapeutics for coronaviruses. There have been some commentaries and communications addressing this area. We have summarized and illustrated the significance and the potential of the siRNA therapeutics available as of April 30, 2021 to combat the ongoing viral pandemic and the emerging new variants such as B.1.1.7 and B.1.351. Numerous successful in vitro studies and several investigations to address the clinical application of siRNA therapeutics provide great hope in this field. This seminal Review describes the significance of siRNA-based therapy to treat diverse viral infections in addition to the current coronavirus challenge. In addition, we have thoroughly reviewed the patents approved for coronaviruses, the major challenges in siRNA therapy, and the potential approaches to address them, followed by innovation and prospects.

Cyclic peptide-selenium nanoparticles as drug transporters.

A cyclic peptide composed of five tryptophan, four arginine, and one cysteine [W5R4C] was synthesized. The peptide was evaluated for generating cyclic peptide-capped selenium nanoparticles (CP-SeNPs) in situ. A physical mixing of the cyclic peptide with SeO3(-2) solution in water generated [W5R4C]-SeNPs via the combination of reducing and capping properties of amino acids in the peptide structure. Transmission electron microscopy (TEM) images showed that [W5R4C]-SeNPs were in the size range of 110-150 nm. Flow cytometry data revealed that a fluorescence-labeled phosphopeptide (F'-PEpYLGLD, where F' = fluorescein) and an anticancer drug (F'-dasatinib) exhibited approximately 25- and 9-times higher cellular uptake in the presence of [W5R4C]-SeNPs than those of F'-PEpYLGLD and dasatinib alone in human leukemia (CCRF-CEM) cells after 2 h of incubation, respectively. Confocal microscopy also exhibited higher cellular delivery of F'-PEpYLGLD and F'-dasatinib in the presence of [W5R4C]-SeNPs compared to the parent fluorescence-labeled drug alone in human ovarian adenocarcinoma (SK-OV-3) cells after 2 h of incubation at 37 °C. The antiproliferative activities of several anticancer drugs doxorubicin, gemcitabine, clofarabine, etoposide, camptothecin, irinotecan, epirubicin, fludarabine, dasatinib, and paclitaxel were improved in the presence of [W5R4C]-SeNPs (50 µM) by 38%, 49%, 36%, 36%, 31%, 30%, 30%, 28%, 24%, and 17%, respectively, after 48 h incubation in SK-OV-3 cells. The results indicate that CP-SeNPs can be potentially used as nanosized delivery tools for negatively charged biomolecules and anticancer drugs.