Bacteriolyses by Zn2+-induced PGN autolysins, and virucides by Zn2+ released from ZAP, ZnONPs against 2019-nCoV prevention, respiratory and pulmonary COVID-19

Abstract

Bacteriolyses of bacterial cell walls by Zn²⁺-induced peptidoglycan autolysins, and virucides by zinc-finger antiviral protein (ZAP), zinc binding domain (ZBD), zinc oxide nanoparticles (ZnONPs) against human coronavirus and 2019-nCoV or COVID-19 infection are discussed respectively.  Bacterial peptidoglycan (PGN) autolysin AmiA for S. aureus amidase is acted on PGN binding and cleavage. The AmiA distinguishes PGN mostly by the peptide, and the cleavage is facilitated by a zinc-activated water molecule, in order to develop new therapeutics against MRSA. Lytic amidase autolysin LytA associates with the cell wall via its zinc-binding motif.  Autolysin LytF is endopeptidase in B. subtilis that plays a role in cell separation and hydrolase of the peptide. Thus, Zn²⁺ ions induced PGN autolysins for S. aureus is amidase LytA and endopeptidase LytM that are anticipated to be used as antibacterial potential of endogenous PGN-degrading enzymes against S. aureus.  Zinc-dependent endopeptidases (Eps) are predicted to hydrolyze PGN to facilitate cell growth that zinc availability affects strong activity of cell wall hydrolases, and zur-regulated endopeptidases are present in divergent Gram-negative bacteria. AmiB catalyzes the degradation of PGN in Gram-negative bacteria, resulting in a marked increases of sensitivity to oxidative stress and organic acids.   Eps at outer membrane lipoprotein and amidase, peptidase, and carboxy-peptidase in PGN layer against E. coli are anticipated to be employed as E. coli cell wall-hydrolyzing enzymes of anti-bacterial potential. Zinc-dependent PGN autolysin of amidases are enhanced the anti-bacterial activities against both Gram-positive and Gram-negative bacteria. The autolysin-mediated bacteriolysis induced bacterial cell death can contribute to the bactericidal activities. On the other hand, enveloped viruses enter cells and initiate disease-causing cycles of replication in virus-cell interaction. ZNF ZCCHC3 binds RNA and facilitates viral RNA that is critical for RIG-1 like receptor (RLR)-mediated innate immune response to RNA virus. ZAP inhibits entry, replication, and spread of certain viruses, and promotes viral RNA degradation. ZAP also may regulate DNA and RNA virus replication that ZAP controls Retroviral RNA production and HIV-1 infection by promoting the degradation of specific viral mRNAs. ZBD inhibits Nidovirus RNA synthesis and replication, hence the 2019-nCoV may be regulated by ZBD. ZnONPs recently are used in various applications of veterinary science due to their antibacterial and antiviral agents, tissue repair that the ZnONPs are anticipated to be employed in prevention of human coronavirus infection. 2019-nCoV is RNA virus that has high mutation rate, and these high rates are correlated with enhanced virulence and evolvability, traits considered beneficial for viruses. 2019-nCoV (β-CoV) structure has a spike glycoprotein (S) that the coronavirus protein mediates coronavirus entry into host cells which the evolution of these two critical functions of coronavirus spike proteins, receptor recognition and membrane fusion must be considered to be able to degrade or suppress for the spikes and the membrane by Zn²⁺-centered tetrahed-rally coordinated binding. Zinc ions could inhibit virus entry and membrane fusion of S1 and S2 domains of spike protein with zinc ion-binding interaction. Zn²⁺ ions can prevent in the early stage of 2019-nCoV infected patient with antiviral zinc homeostatic immunity and have important roles for respiratory and pulmonary process of COVID-19 disease.  The antiviral compounds including zinc N-ethyl-N-phenyldithiocarbamate (EPDTC) inhibit the viral protease, preventing humancoxsackie virus strain B3 (CVB3) genome replication. The interactions had been found on the binding specificity by Zn²⁺ ions-centered tetrahedral geometric coordination of the inhibitors against 3C and 3C-like proteases. Thus, Zinc ion drug development is anticipated to be adopted by using ZAP viral gradation via cell surface receptors and Zn²⁺-coordination pattern, causing to lead enhancement of the anti-viral activity.