Teriflunomide and COVID-19: A Friend or Foe?!

Unfortunately, the coronavirus disease 2019 (COVID-19) pandemic has become an irritating universal crisis. Thus, the discovery/identification of prospective drug candidates to disband the branched health issues caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become urgent. This current research sheds light on the repositioning possibility of the potent antirheumatic drug teriflunomide to act as an efficient anti-SARS-CoV-2/anti-COVID-19 remedy. Herein, a motivating in silico molecular docking/modeling study of teriflunomide explores its potential inhibitory actions on the novel coronaviral-2 RNA-dependent RNA polymerase (nCoV-RdRp) enzyme/protein was reported. Interestingly, the computational analysis of the teriflunomide superior inhibitory binding mode in the binding cavity of one of the active sites of the nCoV-RdRp detected that teriflunomide molecule shows considerably stronger inhibitory binding interactions and better inhibitory binding affinities (it shows lower binding energies which reached -9.70 kcal/mol) than both used references. It was reported that teriflunomide potently impairs viral replication/reproduction by employing two distinct action mechanisms. Thus, the existing study's findings surprisingly uphold teriflunomide's double mode of action. In conclusion, the presented research work paves the way to biologically and clinically begin exploring the promising properties of teriflunomide to strongly hit the SARS-CoV-2 particles of the different strains and inhibit their pathogenic replication in an integrative triple mode of action. Hopingly, the potential sextet COVID-19 attacker teriflunomide can be rapidly subjected to the various in vitro/in vivo/clinical anti-COVID-19 assays/trials in a serious attempt to assess its comprehensive bioactivities against COVID-19 to be effectively used in SARS-CoV-2 infections therapy soon.