ABSTRACT
Small interfering RNA (siRNA)-mediated mRNA degradation approach have imparted its eminence against several difficult-to-treat genetic disorders and other allied diseases. Viral outbreaks and resulting pandemics have repeatedly threatened public health and questioned human preparedness at the forefront of drug design and biomedical readiness. During the recent pandemic caused by the SARS-CoV-2, mRNA-based vaccination strategies have paved the way for a new era of RNA therapeutics. RNA Interference (RNAi) based approach using small interfering RNA may complement clinical management of the COVID-19. RNA Interference approach will primarily work by restricting the synthesis of the proteins required for viral replication, thereby hampering viral cellular entry and trafficking by targeting host as well as protein factors. Despite promising benefits, the stability of small interfering RNA in the physiological environment is of grave concern as well as site-directed targeted delivery and evasion of the immune system require immediate attention. In this regard, nanotechnology offers viable solutions for these challenges. The review highlights the potential of small interfering RNAs targeted toward specific regions of the viral genome and the features of nanoformulations necessary for the entrapment and delivery of small interfering RNAs. In silico design of small interfering RNA for different variants of SARS-CoV-2 has been discussed. Various nanoparticles as promising carriers of small interfering RNAs along with their salient properties, including surface functionalization, are summarized. This review will help tackle the real-world challenges encountered by the in vivo delivery of small interfering RNAs, ensuring a safe, stable, and readily available drug candidate for efficient management of SARS-CoV-2 in the future.
ABSTRACT
RNAi (RNA interference)-based technology is emerging as a versatile tool which has been widely utilized in the treatment of various diseases. siRNA can alter gene expression by binding to the target mRNA and thereby inhibiting its translation. This remarkable potential of siRNA makes it a useful candidate, and it has been successively used in the treatment of diseases, including cancer. However, certain properties of siRNA such as its large size and susceptibility to degradation by RNases are major drawbacks of using this technology at the broader scale. To overcome these challenges, there is a requirement for versatile tools for safe and efficient delivery of siRNA to its target site. Lipid nanoparticles (LNPs) have been extensively explored to this end, and this paper reviews different types of LNPs, namely liposomes, solid lipid NPs, nanostructured lipid carriers, and nanoemulsions, to highlight this delivery mode. The materials and methods of preparation of the LNPs have been described here, and pertinent physicochemical properties such as particle size, surface charge, surface modifications, and PEGylation in enhancing the delivery performance (stability and specificity) have been summarized. We have discussed in detail various challenges facing LNPs and various strategies to overcome biological barriers to undertake the safe delivery of siRNA to a target site. We additionally highlighted representative therapeutic applications of LNP formulations with siRNA that may offer unique therapeutic benefits in such wide areas as acute myeloid leukaemia, breast cancer, liver disease, hepatitis B and COVID-19 as recent examples.
ABSTRACT
The recent outbreak of Coronavirus Disease 2019 (COVID-19) calls for rapid mobilization of scientists to probe and explore solutions to this deadly disease. A limited understanding of the high transmissibility of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) relative to other coronavirus strains guides a deeper investigation into the virus/receptor interactions. The cutting-edge studies in thermodynamic and kinetic properties of interactions such as protein-protein interplays have been reviewed in many modeling and analysis studies. Highlighting the thermodynamic assessments of biological interactions and emphasizing the boosted transmissibility of SARS-CoV-2 despite its high similarity in structure and sequence with other coronavirus strains is an important and highly valuable investigation that can lead scientists to discover analytical and fundamental approaches in studying virus's interactions. Accordingly, we have attempted to describe the crucial factors such as conformational changes and hydrophobicity particularities that influence on thermodynamic potentials in the SARS-COV-2 S-protein adsorption process. Discussing the thermodynamic potentials and the kinetics of the SARS-CoV-2 S-protein in its interaction with the ACE2 receptors of the host cell is a fundamental approach that would be extremely valuable in designing candidate pharmaceutical agents or exploring alternative treatments.
ABSTRACT
A novel SARS-like coronavirus (severe acute respiratory syndrome-related coronavirus-2, SARS-CoV-2) outbreak has recently become a worldwide pandemic. Researchers from various disciplinary backgrounds (social to natural science, health and medicine, etc.) have studied different aspects of the pandemic. The current situation has revealed how the ongoing development of nanotechnology and nanomedicine can accelerate the fight against the novel viruses. A comprehensive solution to this and future pandemic outbreaks includes preventing the spread of the virus through anti-viral personal protective equipment (PPE) and anti-viral surfaces, plus efforts to encourage behavior to minimize risks. Studies of previously introduced anti-viral biomaterials and their optimization to fight against SARS-CoV-2 is the foundation of most of the recent progress. The identification of non-symptomatic patients and symptomatic patients is vital. Reviewing published research highlights the pivotal roles of nanotechnology and biomaterials in the development and efficiency of detection techniques, e.g., by applying nanotechnology and nanomedicine as part of the road map in the treatment of coronavirus disease 2019 (COVID-19) patients. In this review, we discuss efforts to deploy nanotechnology, biomaterials, and stem cells in each step of the fight against SARS-CoV-2, which may provide a framework for future efforts in combating global pandemics.
ABSTRACT
COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against the virus. This approach allows specific binding and silencing of therapeutic targets by using short interfering RNA (siRNA) and short hairpin RNA (shRNA) molecules. In this review, we lay out the prospect of the RNAi technology for combatting the COVID-19. We first summarize current understanding of SARS-CoV-2 virology and the host response to viral entry and duplication, with the purpose of revealing effective RNAi targets. We then summarize the past experience with nucleic acid silencers for SARS-CoV, the predecessor for current SARS-CoV-2. Efforts targeting specific protein-coding regions within the viral genome and intragenomic targets are summarized. Emphasizing non-viral delivery approaches, molecular underpinnings of design of RNAi agents are summarized with comparative analysis of various systems used in the past. Promising viral targets as well as host factors are summarized, and the possibility of modulating the immune system are presented for more effective therapies. We place special emphasis on the limitations of past studies to propel the field faster by focusing on most relevant models to translate the promising agents to a clinical setting. Given the urgency to address lung failure in COVID-19, we summarize the feasibility of delivering promising therapies by the inhalational route, with the expectation that this route will provide the most effective intervention to halt viral spread. We conclude with the authors' perspectives on the future of RNAi therapeutics for combatting SARS-CoV-2. Since time is of the essence, a strong perspective for the path to most effective therapeutic approaches are clearly articulated by the authors.