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Nucleic Acid-Based Anti-monkeypox Drug Discovery Solutions
Monkeypox is a rare disease caused by monkeypox virus infection. In recent years, the monkeypox disease has concentrated and spread rapidly. Based on our extensive experience and advanced platforms, now Creative Biolabs provides novel nucleic acid-based anti-monkeypox drug discovery services for our clients all over the world.
Overview of Nucleic Acid-based Therapy
Viruses are the simplest and most abundant life forms on earth. The replication of a virus depends on the delivery of its genome to a host cell, which subsequently produces viral proteins using the host cell. This process can cause damage to host cells and cause disease. Theoretically, nucleic acids-based antiviral therapeutics are dedicated to inhibiting the expression of viral or host factor genes via DNA or RNA. It is important to note that if the targeted host factors have important cellular functions, their silencing may lead to toxicity. In addition, the simultaneous inhibition of multiple viral targets by a combinatorial approach is also a strategy for coping with the viral infection.
Nucleic acid therapy is based on nucleic acid or its closely related compounds and can be divided into several different groups according to their target molecules, which include target viral proteins, target viral or cellular nucleic acids, as well as target viral nucleic acids or viral proteins
Figure.1 Virus life cycle and possible antiviral mechanism. (Reza, 2021)
Antisense oligonucleotides (ASOs) refer to synthetic chains of nucleotides targeting any genes of interest. According to Watson-Crick base pairing or Hoogsteen base pairing, ASO can bind to the transcribed messenger RNA (mRNA) of the target gene and then modulate gene expression. Compared with traditional drugs targeting proteins, ASO presents various advantages, such as simplicity in design and higher specificity.
Ribozymes are single-stranded RNA molecules that specifically inhibit viral gene expression and replication. Without the requirement of any protein, ribozymes can complex with the target sequences and hydrolyze the target site. Ribozymes are always synthesized in vitro and subsequently delivered into the cell by different transfection methods. Currently, a series of ribozymes have been developed against human papillomaviruses (HPV), acquired immunodeficiency syndrome (AIDS), and the hepatitis C virus (HCV).
Deoxyribozymes ia a non-natural variant of ribozymes. Compared with ribozymes, a minimal number of modifications are required for the construction of stable deoxyribozymes, so that reduce the cost of synthesis and the possibility of non-specific toxic effects. With the capability of cleaving RNA molecules with high efficiency and specificity, deoxyribozymes have been considered promising antiviral agents.
Composed of 68 nucleotides, the chimeric RNA/DNA oligonucleotide is a novel tool to correct point or frameshift gene mutations. As a double-stranded molecule, one strand consists entirely of DNA and the other consists of two 10 nt 2'-O-methyl (2'-O-Me) RNA. For the treatment of severe acute respiratory syndrome (SARS), a chimeric DNA-RNA hammerhead ribozyme has been developed to significantly inhibit the proliferation of mouse hepatitis virus (MHV) in DBT cells.
RNA interference (RNAi) is a naturally occurring gene regulatory process to achieve gene silencing through chromatin remodeling, inhibition of protein translation, or direct mRNA degradation. There are three pathways capable of producing double-stranded RNA (dsRNA) molecules that activate RNAi, including microRNA (miRNA), short interfering RNA (siRNA), and short hairpin RNA (shRNA). As a potential therapeutic tool, RNAi plays a role in all stages of the virus life cycle.
Nucleic acid aptamers are single-stranded oligonucleotides (RNA or DNA) 30 to 100 nt long that can bind to and affect the activity of target molecules with high specificity and affinity. Similar to antibodies, aptamers have a very broad range of applications and can treat viral infections in a variety of ways.
Creative Biolabs is a leading service provider that focuses on drug discovery. We can assist you in designing the best research outline customized to meet the requirements of clients' programs. If you are interested in our services and products, please do not hesitate to contact us for more details.
Reza, M.S.; et al. The Possibility of Nucleic Acids to Act as Anti-Viral Therapeutic Agents—A Review. Open Journal of Medical Microbiology. 2021, 11(3): 198-248.