Aptamers are nucleic acids with many of the properties of antibodies, but with the advantage that they are selected and synthesized in vitro and have low to no immunogenicity. With high specificity for their targets and being large enough to cover a portion of a protein surface in order to compete with its binding partner, aptamers are excellent candidate drugs for interfering with the viral-cell interactions. As more GP/surface receptor pairs are identified, the possibility increases of developing drugs to interfere with viral cell entry. A drug that can prevent viral glycoprotein (GP) interaction with its surface receptor can effectively stop infection by enveloped viruses. A limitation in finding aptamers that effectively compete with viral-cell interactions is that the appropriate target sites on the viral GP are protected by cloud of carbohydrate that the aptamer needs to penetrate. Many sites on the purified GP protein are also not accessible when the protein is integrated in the virion. Thus, a simple selection against the purified GP is unlikely to identify the appropriate aptamer and selection against the virion is also unlikely to be sufficient due to the presence of other competing targets that are not involved in virus-cell interaction. This is a general challenge for isolating aptamers to many proteins located on the cell surfaces and integrated in viral particles. Here we propose the application of new technologies including deep sequencing, virion binding analysis on the sequencing microarrays and informatics to the challenge of isolating aptamers with better targeting for relevant cell surface or virion membrane associated proteins. This approach will provide an exciting new opportunity to obtain aptamers that target and block the ability of a GP to interact with its receptor. If successful, this work will provide an aptamer that can be developed as a stopgap measure to minimize deaths from the deadly Ebolavirus outbreaks that are becoming increasingly frequent. The aptamer will also be useful for rapid diagnosis of Ebolavirus infection that first presents as a hemorrhagic fever similar to that associated with other viral diseases.
Aptamers are excellent candidates for drugs that interfere with the entry of viruses into cells. The current proposal will apply a strategy that involves several new technologies to isolate unique aptamers with better targeting for the region of the Ebola virus surface that allows it to infect cells. Being readily stored for long periods, these aptamers could provide the first defense against viral infection when an outbreak occurs.
| Shubham, Shambhavi; Hoinka, Jan; Banerjee, Soma et al. (2018) A 2'FY-RNA Motif Defines an Aptamer for Ebolavirus Secreted Protein. Sci Rep 8:12373 |
