Identification and Analysis of Genomic Homing Endonuclease Target Sites

2014 ◽  
pp. 245-264 ◽  
Author(s):  
Stefan Pellenz ◽  
Raymond J. Monnat
Keyword(s):  
Homing Endonuclease ◽  
Target Sites

Design and Delivery of Therapeutic siRNAs: Application to MERS-Coronavirus

2018 ◽  
Vol 24 (1) ◽  
pp. 62-77 ◽  
Author(s):  
Sayed Sartaj Sohrab ◽  
Sherif Aly El-Kafrawy ◽  
Zeenat Mirza ◽  
Mohammad Amjad Kamal ◽  
Esam Ibraheem Azhar
Keyword(s):  
Enzymatic Degradation ◽  
Polymeric Nanoparticles ◽  
Genetic Disorders ◽  
Inorganic Nanoparticles ◽  
Innovative Technology ◽  
Viral Diseases ◽  
Viral Gene ◽  
Efficient Delivery ◽  
Disease Therapy ◽  
Target Sites

Background: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published. Methods: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential siRNA can be designed to silence a desired gene by considering many factors like target site, specificity, length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses. The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles, inorganic nanoparticles and polymeric nanoparticles. Conclusion: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV.

Fusion Protein Targeted Antiviral Peptides: Fragment-Based Drug Design (FBDD) Guided Rational Design of Dipeptides Against SARS-CoV-2

2020 ◽  
Vol 21 (10) ◽  
pp. 938-947
Author(s):  
Sounik Manna ◽  
Trinath Chowdhury ◽  
Piyush Baindara ◽  
Santi M. Mandal
Keyword(s):  
Public Health ◽  
Drug Design ◽  
Infectious Diseases ◽  
Fusion Protein ◽  
Fusion Process ◽  
Viral Fusion ◽  
Enveloped Viruses ◽  
Antiviral Peptides ◽  
Target Sites ◽  
Tract Infections

: Infectious diseases caused by viruses have become a serious public health issue in the recent past, including the current pandemic situation of COVID-19. Enveloped viruses are most commonly known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major key event in the case of enveloped viruses that is required for their entry into the cell. Viral fusion proteins play an important role in the fusion process and in infection establishment. Because of this, the fusion process targeting antivirals become an interest to fight against viral diseases caused by the enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus (SARS-CoV) are examples of such enveloped viruses that are at the top in public health issues. Here, we summarized the viral fusion protein targeted antiviral peptides along with their mechanism and specific design to combat the viral fusion process. The pandemic COVID-19, severe respiratory syndrome disease is an outbreak worldwide. There are no definitive drugs yet, but few are in on-going trials. Here, an approach of fragmentbased drug design (FBDD) methodology is used to identify the broad spectrum agent target to the conserved region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from the library and designed by the systematic combination along with their possible modifications of amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = - 62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Anyone of the active peptides from the developed libraries may help to block the target sites competitively to successfully control COVID-19.

Sign in / Sign up

Export Citation Format

Share Document