Anti-Infective Activities for Bacterial Zn2+-Induced Peptidoglycan Autolysins and Zinc-Binding Antiviral Proteins against Bacterial and Viral Infections

Anti-infective activities of bacterial Zn2+-induced peptidoglycan (PGN) autolysins and zinc-finger antiviral proteins respectively are discussed against both bacterial and viral infections. Bacterial PGN autolysin AmiA for S. aureus amidase is acted on PGN binding and cleavage that amiA distinguishes PGN mostly by the peptide, and cleavage is facilitated by a zinc-activated molecule. The autolytic activity of the recombinant amidase of the Aas (autolysin/adhesin of Staphylococcus saprophyticus) is inhibited and is neccesary for the C-terminal GW repeats, not the N-terminal repeats. AmiB catalyzes the degradation of PGN in bacteria, resulting in a marked increases of sensitivity to oxidative stress and organic acids. Amidase activity of amiC controls cell separation and PGN fragments release. Lytic amidase autolysin LytA associates with the cell wall via its zinc-binding motif. The LytB PGN hydrolase responsible for physical separation of daughter cells cleaves the GlcNAc-β-(1,4)-MurNAc glycosidic bond of PGN building units. LytC, LytD, and LytF are expressed in the same subpopulation of cells and complete flagellar synthesis. Thus, autolysin mediated bacteriolysis induced bacterial cell death can contribute to the bactericidal activities.

The other, enveloped viruses enter cells and initiate disease-causing cycles of replication that in all cases virus-cell fusion is executed by one or more viral surface glycoproteins denoted as the fusion protein, The novel EBV-induced zinc finger gene, ZNFEB, including human protein variants, controls entry and exit from cell cycling in activated lymphocytes. The designed polydactyl zinc finger protein is prepared consisting HIV-1 type integrase fused to the synthetic zinc finger protein (ZNF) E2C. ZNF ZCCHC3 binds RNA and facilitates viral RNA that ZCCHC3 is a co-receptor for the retinoic acid-inducible gene-1 (RIG-1) and antigen MDA5 which is critical for RIG-1 like receptor (RLR)-mediated innate immune response to RNA virus. ZNF Tsip1 controls Cucumber mosaic virus (CMV) RNA replication. Zinc-finger antiviral protein (ZAP) specifically inhibits the replication of certain viruses and promotes viral RNA degradation, ZAP inhibits alphavirus replication that elucidation of the antiviral mechanism, and ZAP inhibit Sindbis virus translation may lead to the development of agents with broad activity against alphaviruses. ZAP also inhibits HIV-1 infection by promoting the degradation of specific viral mRNAs and inhibits influenza A virus (IAV) protein that the short form of ZAPS inhibited IAV PB2 protein expression by reducing the encoding viral mRNA levels and repressing its translation. Thus, ZAPs findings provide insight into how antiviral components are regulated upon virus infection to inhibit virus spread. Viral infections spread based on the ability of viruses to overcome multiple barriers and move from cell to cell, tissue to tissue, and person to person and even across species with via two distinct routes. HIV-1 cell-to-cell transmission likely contributes to HIV-1 spread that the cell-to-cell transmission is sensitive to neutralization. The host cell restriction factors that mediate anti-influenza virus activity and viral countermeasures, limit influenza A infection that the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

Keywords: Bacterial PGN autolysin, Autolysin amidase, ZAP, Viral entry, replication and spread.