Conformers of a novel lipopeptide antibiotic, Kannurin inhibits SARS-Cov2 replication via interfering with RNA-dependent-RNA polymerase activation and function

Abstract

The key component 'nsp12' of RNA-dependent-RNA polymerase of Corona virus is considered as a primary target for drug intervention purposes. The broad spectrum antimicrobial lipopeptide Kannurin revealed favourable interactions against nsp12 in preliminary in silico experiment. Among the different target sites on nsp12 selected for docking study, the cyclic form of Kannurin was found to interact with the residues Phe 407, Leu 544 and Lys 511 present in the finger subdomain of nsp12 that are facilitating the binding of nsp7 and nsp8 cofactors. Hence it is proposed that Kannurin can act by inhibiting the binding of cofactors with nsp12 and ultimately leading to its inactivation. The second mechanism is by the interaction of linear form of Kannurin with the palm subdomain cavity, specifically with the residue Arg 555 that involved in receiving the incoming nucleotides during replication. The mechanism is closely related to the action of 'Remdesivir'.