On the 24 th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

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The potential antiproliferative effects of interferon‐α (IFN‐α) in the treatment of hepatocellular carcinoma (HCC) are controversial, and the growth inhibitory mechanisms remain poorly understood. Therefore, the current study was designed to delineate the molecular mechanisms responsible for direct antiproliferative actions of IFN‐α in HCC cells. IFN‐α receptor expression and signal transduction were examined by RT‐PCR, immunoprecipitation, Western analysis, and transient transactivation assays. Effects of IFN‐α on cell growth and cell‐cycle distribution were evaluated based on cell numbers and flow cytometry. Composition and activity of cyclin‐dependent kinase complexes were determined by immunoblotting and histone‐H1‐kinase assays. Expression of IFN‐α receptors was found in all 3 HCC cell lines. IFN‐α binding initiated phosphorylation of Jak1 and Tyk2 kinases leading to Stat1/Stat2 activation, nuclear translocation, and transactivation of an ISRE‐luciferase reporter gene construct. IFN‐α treatment resulted in a time‐ and dose‐dependent reduction of proliferation. Cell cycle analysis of G1‐synchronized, IFN‐α‐treated HCC cells revealed a substantial delay in S‐phase progression but no alteration of G1/S‐phase transition or evidence of apoptotic cell death. Reflecting the time course of S‐phase accumulation, cell cycle‐dependent induction of Cyclin A and Cyclin B was impaired, resulting in reduced activity of Cdk2 and Cdc2 kinases. Furthermore, Cdc25C was selectively down‐regulated. IFN‐α treatment inhibits growth of HCC cells by specifically delaying S‐phase progression, most likely because of inhibition of Cyclin A induction, resulting in decreased activity of the associated Cdk2 and Cdc2 kinases.

IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer. Gut 2010;59:69-78.