TABLE 2

Overview of US28-targeting and modulating agents

Molecule ClassMolecule Name/ScaffoldMode of ActionInfection StateIn Vitro/In VivoFunctional EffectReference
Small moleculePiperazinyldibenzothiepins; cinchonine derivates; cinchonidines derivates; arylamines; benzamidesAntagonistsIn vitroLigand blockingVischer et al. (2014)
Methiothepin; Octoclothepin; S-(−)-IodobenzamideAntagonist/partial inverse agonistIn vitroLigand blocking and partial inhibition of US28 constitutive activityVischer et al. (2010)
VUF2274Antagonist/full inverse agonistLatent infectionIn vitroFull reactivation of latently infected cells resulting in T-cell–mediated cell deathCasarosa et al. (2003b); Krishna et al. (2017a)
Derivates of flavonoids; biphenyl amides; CX3CR1 antagonists; VUF2274Agonist; antagonist; inverse agonistIn vitroLigand blocking/enhanced US28 signaling/partial inhibition of US28 constitutive activityKralj et al. (2011), (2013), (2014); Lückmann et al. (2017); Amărandi et al. (2018)
NanobodyUS28-NbAntagonistCancer settingIn vitroLigand blockingHeukers et al. (2018)
Bivalent US28-NbAntagonist/partial inverse agonistCancer settingIn vitro/in vivoPartial inhibition of US28-mediated enhanced glioblastoma tumor growthHeukers et al. (2018)
VUN100-PSAntagonist/photosensitizer-induced cell deathCancer settingIn vitroSelective killing of US28-expressing glioblastoma cellsDe Groof et al. (2019b)
Toxin-coupled chemokineF49A-FTPToxin-induced cell deathLytic infectionIn vitro/in vivoSelective killing of HCMV-infected cellsSpiess et al. (2015b)
Latent infectionIn vitroKrishna et al. (2017b)