Biogenic polyamines spermine and spermidine activate RNA polymerase and inhibit RNA helicase of hepatitis C virus

Abstract

Influence of the biogenic polyamines spermine, spermidine, and putrescine as well as their derivatives on the replication enzymes of hepatitis C virus (HCV) was investigated. It was found that spermine and spermidine activate HCV RNA-dependent RNA polymerase (NS5B protein). This effect was not caused by the stabilization of the enzyme or by competition with template-primer complex, but rather it was due to achievement of true maximum velocity V(max). Natural polyamines and their derivatives effectively inhibited the helicase reaction catalyzed by another enzyme of HCV replication - helicase/NTPase (NS3 protein). However, these compounds affected neither the NTPase reaction nor its activation by polynucleotides. Activation of the HCV RNA polymerase and inhibition of the viral helicase were shown at physiological concentrations of the polyamines. These data suggest that biogenic polyamines may cause differently directed effects on the replication of the HCV genome in an infected cell.

Structural Basis of SARS-CoV-2– and SARS-CoV–Receptor Binding and Small-Molecule Blockers as Potential Therapeutics

“…Polyamines also play pivotal roles in viral genome synthesis, including transcription, translation, and genome packaging (63). Studies of chikungunya, Zika, hepatitis C, and Ebola viruses highlight the enhancement of viral polymerase activity by polyamines (86)(87)(88)(89). Further investigation is needed to understand the role(s) of spermidine in SARS-CoV-2 infection.…”

Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology

“…However, long-lasting expression of viral proteins in the context of the full length replicon resulted in a decrease in spermine and spermidine, accompanied by an induction of spermine oxidase. Spermine oxidase may be required for efficient replication of the viral genome, since polyamines were previously shown to inhibit helicase activity of HCV NS3 protein [ 157 ]. Finally, Chlorella virus that infects some algae species encodes enzymes of polyamine biosynthesis itself [ 158 , 159 ].…”

Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1

“…The role played by polyamines in viral genome transcription has also been reported, such as in Marburgvirus and in Ebola virus ( Olsen et al, 2018 ; Olsen et al, 2016 ). The activity of viral polymerases and proteases, specifically HCV, HSV-1 and Coxsackievirus B3 (CVB3), was shown to be regulated by polyamines as well ( Dial et al, 2019 ; Korovina et al, 2012 ; Wallace et al, 1980 ). Interestingly, polyamines also play a role in the attachment stage of CVB3 during its infection ( Kicmal et al, 2019 ).…”