Objective To investigate the impact of 5-fluorouracil (5-FU) and cisplatin on miR-449b expression in human hepatocellular carcinoma (HCC) and elucidate the molecular mechanism of 5-FU and cisplatin inhibiting the migration of HCC cells.Methods Real-time qPCR analysis was conducted to determine the expression of miR-449b in 50 HCC tissues.RT-PCR assay was performed to detect the expression of miR-449b in HCC cells with 5-FU and cisplatin treatment.The migration of HCC cells with the overexpression of miR-449b was determined by wound-healing assay;Rescue assay was employed to investigate the correlation between 5-FU & cisplatin, miR-449b and the migration capacity of HCC cells;The putative targets of miR-449b were predicted and validated using target prediction programs and immunoblots.Results The expression of miR-449b decreased in HCC tissues (P<0.0001).miR-449b expression increased in HCC cells upon the treatment of 5-FU and cisplatin (P<0.001).The overexpression of miR-449b inhibited the migration of HCC cells (P<0.001).Rescue assay revealed that inhibition of miR-449b to prevent 5-FU and cisplatin induction resulted in suppressed migration in SMMC7721 cells(P<0.05).Catenin-δ was a functional target of miR-449b.Conclusions 5-FU and cisplatin inhibit the migration of HCC cells at least partly via inducing the expression of miR-449b.

The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C^pro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (M^pro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of M^pro to inhibit its activity. We demonstrate that targeting the active site cysteine of M^pro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.