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 have 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.

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