The recognition of stem-loop-based RNA structures by coat proteins plays a crucial role in the assembly of many viruses, thus interfering with encapsulation protein recognition by RNA-drug interaction could be a promising strategy for antiviral therapeutics. Tylophorine B showed selectively high affinity for the assembly origin of tobacco mosaic virus RNA, furthermore disrupted in vitro virus assembly through small-molecule-RNA interactions. According to the interaction model, a series of indolocarbazole compounds based on tylophorine B backbone were synthesized. In vivo anti-viral activity showed the protection and curative effect of indolocarbazole with the structure of pyrrolidine at the concentration of 500 �g/mL were 33.3% and 40.5%, respectively, which were a bit higher than that of the commecial anti-viral drug ribovirin, 32.8% and 36.2%, respectively. Our work might shed light on a new antiviral strategy: targeting viral RNA with small molecules to inhibit viral assembly by rational design of antiviral drugs.

Design and synthesis of antivirals based on tobacco mosaic virus assembly inhibition

248th National Meeting (2014)

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