Human cytomegalovirus protease (Assemblin) (HCMV protease)

Human cytomegalovirus (HCMV) protease, also known as assemblin, is a virally encoded serine protease essential for the replication of HCMV, a member of the Betaherpesvirinae subfamily [9, 11]. It is encoded by the UL80 gene and plays a critical role in the maturation of the viral capsid by cleaving the assembly protein precursor (pUL80.5) [11, 15]. This proteolytic processing is required to remove the internal scaffolding from the procapsid, allowing for the packaging of the viral DNA and the formation of infectious virions [6, 11]. Structurally, HCMV protease is unique among serine proteases, featuring a novel fold and a Ser-His-His catalytic triad (Ser132, His63, His157) that differs from the classic Ser-His-Asp triad found in human proteases [9, 15]. HCMV is a major cause of morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients, and is a leading cause of congenital infections [13, 18]. The structural uniqueness of the HCMV protease makes it an attractive therapeutic target for highly specific antiviral drugs, as inhibitors can be designed to minimize cross-reactivity with host enzymes [7, 15]. While several experimental inhibitors, including peptidomimetics and monocyclic beta-lactam derivatives, have been investigated, no protease inhibitors are currently approved for clinical use [7, 14]. Additionally, the protease is being explored for the site-specific activation of prodrugs, such as ganciclovir derivatives, to improve efficacy and reduce systemic toxicity [5].

Other names

AssemblinUL80 proteaseHHV-5 proteaseMaturational proteaseHuman betaherpesvirus 5 protease

Inhibition of the proteolytic cleavage of the viral assembly protein precursor, which prevents capsid maturation and the production of infectious virions.