DEVELOPMENT OF TOPICAL ANTIVIRAL AGENTS FOR TREATING MOLLUSCUM CONTAGIOSUM

DESCRIPTIONprovided by applicantMolluscum contagiosumMCis a highly contagious skin disease caused by the poxvirusMCVMC appears as lesions on the body and face and can last months years before resolvingLesions occur most frequently in childrenand immune compromised individualsThe infection is confined to skin aloneit is not systemicTransmission spreads directly from person person contactautoinoculationscratchingor indirect contact e gtowelsCurrent treatments can be painfulcause scarringpigmentation and psychological distressespecially to children and parentsNone of the current treatments that include a range of physicalchemical and medicinal interventions are uniformly accepted or FDA approvedNo drug has ever been specifically developed for MC because MCV cannot be grown in any type of cultured cell for the purpose of testing new compoundsWe have now made FOUR MAJOR BREAKTHROUGHSFIRSTwe have identified a novel protein target in MCVmDthat is essential for viral replicationmDis a processivity factorwhich together with its hetero dimeric partner mAtether the viral Polymerase to the template to enable synthesis of long strands of DNASECONDwe have discoveredsmall molecule inhibitors with different scaffolds that target the mDPF and block long chain DNA synthesis in vitroTHIRDwe have constructed a new infectious Vaccinia hybrid virusmDVVthat expresses the mDtarget protein and is inhibited from infecting cells by allcompoundsThe mDVV hybrid virus is a major advancement for MC drug development since it provides the first cell based system for screening therapeutics against an essential MCV target proteinmDin poxvirus infected cellsFOURTHwe have now shown the surrogate hybrid virusmDVVcan infectD human skin organ culturesequivalent to human skinand that our most potent lead compoundhas antiviral activity in this systemThusfor the first timewe havea protein targetmDessential for MCV replicationa new surrogate hybrid virus for optimizing analogs directed against the mDviral targeta natural humanD skin organ culture for testing antiviral activity andseveral compounds with antiviral activityAIMSare tightly interconnected in which medicinal chemistry will be applied in an iterative process to optimize drug efficacy and safety through progressive steps that test for inhibition and binding to the target proteinpotent antiviral efficacy in cell and humanD skin organ culturesskin penetration and safetyand efficacy in a cutaneous mouse model of infection with mDVVThe specific goal of this Phase II SBIR will be the identification ofor more advanced leads suitable for IND enabling studiesThe ultimate goal of our program is to provide a topical skin formulation that will safely and rapidly resolve MC lesions that occur mainly in children and immune compromised patients