Hepatitis A virus 3C cysteine proteinase (HAV 3Cpro)

The Hepatitis A virus (HAV) 3C cysteine proteinase, commonly referred to as 3Cpro or picornain 3C, is an essential enzyme for the replication and maturation of the hepatitis A virus [1, 12]. It belongs to the picornain family of cysteine proteases but is structurally characterized by a chymotrypsin-like fold, featuring a catalytic triad typically composed of His44, Asp84, and Cys172 [3, 5, 11]. The primary biological function of HAV 3Cpro is the proteolytic processing of the viral polyprotein into mature structural and non-structural proteins, a step indispensable for the assembly of new virions [10, 14]. Beyond its role in polyprotein cleavage, the enzyme facilitates viral immune evasion by cleaving host proteins involved in the innate immune response, such as MAVS, TRIF, and NEMO, thereby suppressing interferon production [9, 12, 14]. It also possesses RNA-binding capabilities that assist in viral genome replication [8]. Due to its critical role in the viral life cycle and its distinct substrate specificity, HAV 3Cpro is a primary target for the development of direct-acting antiviral therapies [2, 6]. Research into inhibitors includes various chemical classes such as beta-lactones, peptide aldehydes, and heteroaromatic esters, which aim to block the enzyme's active site and halt viral progression [1, 4, 7].

Other names

3C protease3CproPicornain 3CHAV 3C proteinaseHepatitis A virus-type picornain 3C

Inhibition of the cysteine protease activity by binding to the active site (Cys172), thereby blocking the cleavage of the viral polyprotein and host immune signaling proteins.