Amantadine and Rimantadine Analogues—Single-Crystal Analysis and Anti-Coronaviral Activity

Abstract

In this study, we utilized the human coronavirus 229E (HCoV-229E) for evaluating the in vitro efficacy of some analogues of the ion-channel inhibitors and Amantadine and Rimantadine. The application of these investigated compounds did not result in any detectable cytotoxic effects. Furthermore, we observed that the derivatives of both analogues did not affect the viability of MDBK cells. Amantadine and Rimantadine applied at a concentration of 50 μg/mL inhibited the replication by 47% and 36%, respectively. The derivatives of Amantadine displayed a slightly weaker inhibitory effect in comparison with its own inhibitory effect. The derivative 4R of Rimantadine exhibited the same antiviral effect as the Rimantadine control, inhibiting viral replication by 37%. However, the other two derivatives of Rimantadine demonstrated lower activities. The molecular structures of the newly synthesized compounds were investigated thoroughly using single-crystal X-ray analysis. Molecular docking studies were performed using Autodock Vina. Two of the studied compounds 2A and 4A showed a promising binding affinity (−8.3 and −8.0 kcal/mol) towards SARS-CoV-2 RNA-dependent polymerase RNA site and SARS-CoV-2 Nsp3 (207-379, MES site) respectively.

Keywords

• Amantadine
• Rimantadine
• X-ray analysis
• antiviral activity
• coronavirus