The reaction mechanism of the NS3/NS4A protease with the NS4B/5A and NS4A/4B natural substrates has been investigated using the QM/MM (quantum mechanics/molecular mechanics) approach, and some calculations have been performed on the reaction with the NS5A/5B natural substrate. This study widely extends a previous contribution of our group on the reaction mechanism with the NS5A/5B substrate, th...

members of the Pestivirus genus of the Flaviviridae family causes significant economic losses worldwide to the agricultural industry (Theil et al., 1996). Bovine viral diarrhoea virus (BVDV) has served as the prototype species for this genus, as well as a surrogate virus for hepatitis C virus drug development (Baginski et al., 2000; Bukhtiyarova et al., 2002). BVDV, a positive single-stranded R...

The complete genome sequence of a sub-subgenotype 2.1i isolate of classical swine fever virus (CSFV), GD317/2011, was determined. Notably, GD317/2011 is distant from the sub-subgenotype 2.1b isolate HEBZ at genes of Erns, E1, E2, P7, NS2, NS5A and the 3'-nontranslated region (3'-NTR) but is closely related to that at genes of Npro, Core, NS3, NS4A, NS4B, and NS5B.

Rapid emergence of resistance to monotherapy with virus-specific inhibitors necessitates combination therapy. ACH-806 is a hepatitis C virus NS4A inhibitor with a novel mechanism of action and resistance pathway. This compound was synergistic with NS3 protease inhibitors and NS5B nucleoside and nonnucleoside polymerase inhibitors.

The hepatitis C virus (HCV) nonstructural (NS)3-NS4A serine protease heterocomplex is a prime target for development of novel HCV therapies, due to its essential role in maturation of the viral polyprotein. While the mode of substrate/inhibitor recognition of the HCV NS3/NS4A serine protease has been extensively studied in vitro, important molecular aspects of the mechanism of action for this m...

The viruses of the family Flaviviridae possess a positive-strand RNA genome and express a single polyprotein which is processed into functional proteins. Initially, the nonstructural (NS) proteins, which are not part of the virions, form complexes capable of genome replication. Later on, the NS proteins also play a critical role in virion formation. The molecular basis to understand how the sam...

The N-terminal 198 residues of NS3 (NS3-N) of Hepatitis C virus (HCV) subtype 1b obtained from 29 patients, as well as full-length NS3 (NS3-Full), were analysed for their subcellular localization, interaction with the tumour suppressor p53 and serine protease activity in the presence and absence of the viral cofactor NS4A. Based on the subcellular-localization patterns in the absence of NS4A, N...