“…The incorporation of one or more halogen atoms, especially the fluorine atom, into nucleoside analogs improved their pharmacological properties [ 10 , 11 ]. Recently, multiple research teams have discovered and developed novel 2′-deoxy-2′,2′-dihalonucleosides/tides with high potency against HCV NS5B polymerase [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Some of those analogs (e.g., compounds 6, 8, and 12) displayed better potency as compared to the marketed drug Sofosbuvir [ 12 ] due to the similarity of the van der Waal’s radius of the chlorine atom or bromine with the methyl group, which could provide the steric interference and the polarizability to terminate the RNA chain elongation of the viral replication ( Table 1 ).…”