Antiviral drug acyclovir exhibits antitumor activity via targeting βTrCP1: Molecular docking and dynamics simulation study

Remission of HPV-Related Diseases by Antivirals for Herpesvirus: Clinical Cases and a Literature Review

“…ACV exhibits antitumor activity targeting βTrCP1, one of the four ubiquitin-protein ligase complex subunits, which regulates multiple cellular processes mediating the degradation of various targets [44,45]. E7 of several HPV genotypes targets βTrCP1, modulating the proteasome activity of the infected cells, suggesting a possible effect of ACV on the HPV life cycle.…”

“…ACV exhibits antitumor activity targeting βTrCP1, one of the four subunits of the ubiquitin protein ligase complex. It has been proposed that ACV abolishes βTrCP1 ligase activity toward the ubiquitination of substrates [44]. Interestingly, is upregulated by the HPV16 E7 oncoprotein [45] and interacts not only with E7 from high-risk alpha HPVs (HPV16, 18, 33, and 39), but also with E7 from beta HPV genotypes (HPV8, 38, and 49), indicating that this target of the HPV protein may be necessary for viral persistence and carcinogenesis [46].…”

The effects of Acyclovir administration to NCI-H1975 non-small cell lung cancer cells

“…Acyclovir (ACV) is a synthetic guanosine analogue that has gained attention not only for its well documented antiviral activity against human herpesviruses (HHVs) (Schaeffer, 1982;Elion, 1993), but also for its potential application as an anticancer drug (Alibek et al, 2012). Indeed, other than its possible use in cytomegalovirus-positive glioblastoma (Solomon et al, 2014), other proposed mechanisms by which ACV could be employed in cancer therapy concern the inhibition of indoleamine 2,3-dioxygenase activity and of βTrCP1 ligase activity (Söderlund et al, 2010;Shafique and Rashid, 2017). The first enzyme is involved in developing immunosuppressive lymphocytes and immunologic tolerance in the tumour microenvironment (Godin-Ethier et al, 2011); the latter is involved in the targeted degradation of various growth and survival factors via ubiquitin-mediated pathway (Frescas and Pagano, 2008).…”