Fleximers are different series of flexible, or “split” purine base analogues designed to learn how nucleobase flexibility affects the recognition, binding, and activity of nucleoside(tide) analogues. There is a purine base scaffold in the fleximers. With this purine base scaffold, the imidazole and pyrimidine moieties are combined by a single carbon-carbon bond, rather than being “fused” as is typical for the purines.

In previous reports, a number of novel fleximers have been screened, and these fleximers can combine the flex-base motif with the flexible acyclic sugar scaffold of the FDA-approved drug acyclovir (serves as a polymerase inhibitor). Studies demonstrated that these fleximers can inhibit HCoV-NL63 and MERS-CoV replication in cell culture. However, it is still unknown how these novel analogues disrupt viral replication. In summary, acyclovir fleximers for SARS-CoV-2 are a group of promising drug candidates for the new drug discovery.