Antiviral peptides against SARS-CoV-2: therapeutic targets, mechanistic antiviral activity, and efficient delivery.

The global pandemic of COVID-19 is a serious public health concern. Over 625 million confirmed cases and more than 6 million deaths have been recorded worldwide. Although several vaccines and antiviral medications have been developed, their efficacy is limited by the emerging new SARS-CoV-2 strains. Peptide-based therapeutics is a fast-growing class of new drugs and have unique advantages over large proteins and small molecules. Antiviral peptides (AVPs) are short polycationic antivirals with broad-spectrum effects, which have been shown to exert both prophylactic and therapeutic actions against reported coronaviruses. The potential therapeutic targets of AVPs are located either on the virus (e.g., E-protein and S-protein) to prohibit viral binding or host cells, particularly, those present on the cell surface (e.g., ACE2 and TMPRSS2). Despite AVPs having promising antiviral effects, their efficacy is limited by low bioavailability. Thus, nanoformulation is a prerequisite for prolonged bioavailability and efficient delivery. This review aimed to present an insight into the therapeutic AVP targets on both virus and host cells by discussing their antiviral activities and associated molecular mechanisms. Besides, it described the technique for discovering and developing possible AVPs based on their targets, as well as the significance of using nanotechnology for their efficient delivery against SARS-CoV-2.

Development of a Polysaccharide-Based Hydrogel Drug Delivery System (DDS): An Update.

Delivering a drug to the target site with minimal-to-no off-target cytotoxicity is the major determinant for the success of disease therapy. While the therapeutic efficacy and cytotoxicity of the drug play the main roles, the use of a suitable drug delivery system (DDS) is important to protect the drug along the administration route and release it at the desired target site. Polysaccharides have been extensively studied as a biomaterial for DDS development due to their high biocompatibility. More usefully, polysaccharides can be crosslinked with various molecules such as micro/nanoparticles and hydrogels to form a modified DDS. According to IUPAC, hydrogel is defined as the structure and processing of sols, gels, networks and inorganic-organic hybrids. This 3D network which often consists of a hydrophilic polymer can drastically improve the physical and chemical properties of DDS to increase the biodegradability and bioavailability of the carrier drugs. The advancement of nanotechnology also allows the construction of hydrogel DDS with enhanced functionalities such as stimuli-responsiveness, target specificity, sustained drug release, and therapeutic efficacy. This review provides a current update on the use of hydrogel DDS derived from polysaccharide-based materials in delivering various therapeutic molecules and drugs. We also highlighted the factors that affect the efficacy of these DDS and the current challenges of developing them for clinical use.