Nucleic Acid-Based COVID-19 Therapy Targeting Cytokine Storms: Strategies to Quell the Storm.

Coronavirus disease 2019 (COVID-19) has shaken the world and triggered drastic changes in our lifestyle to control it. Despite the non-typical efforts, COVID-19 still thrives and plagues humanity worldwide. The unparalleled degree of infection has been met with an exceptional degree of research to counteract it. Many drugs and therapeutic technologies have been repurposed and discovered, but no groundbreaking antiviral agent has been introduced yet to eradicate COVID-19 and restore normalcy. As lethality is directly correlated with the severity of disease, hospitalized severe cases are of the greatest importance to reduce, especially the cytokine storm phenomenon. This severe inflammatory phenomenon characterized by elevated levels of inflammatory mediators can be targeted to relieve symptoms and save the infected patients. One of the promising therapeutic strategies to combat COVID-19 is nucleic acid-based therapeutic approaches, including microRNAs (miRNAs). This work is an up-to-date review aimed to comprehensively discuss the current nucleic acid-based therapeutics against COVID-19 and their mechanisms of action, taking into consideration the emerging SARS-CoV-2 variants of concern, as well as providing potential future directions. miRNAs can be used to run interference with the expression of viral proteins, while endogenous miRNAs can be targeted as well, offering a versatile platform to control SARS-CoV-2 infection. By targeting these miRNAs, the COVID-19-induced cytokine storm can be suppressed. Therefore, nucleic acid-based therapeutics (miRNAs included) have a latent ability to break the COVID-19 infection in general and quell the cytokine storm in particular.

Phage-choline Kinase Inhibitor Combination to Control Pseudomonas aeruginosa: A Promising Combo.

BACKGROUND: Pseudomonas aeruginosa is one of the most prevalent opportunistic pathogens in humans that has thrived and proved to be difficult to control in this "post-antibiotic era." Antibiotic alternatives are necessary for fighting against this resilient bacterium. Even though phages might not be "the wonder drug" that solves everything, they still provide a viable option to combat P. aeruginosa and curb the threat it imposes. MAIN FINDINGS: The combination of antibiotics with phages, however, poses a propitious treatment option for P. aeruginosa. Choline kinase (ChoK) is the enzyme that synthesizes phosphorylcholine subsequently incorporated into lipopolysaccharide located at the outer membrane of gram-negative bacteria. Recently, inhibition of ChoKs has been proposed as a promising antibacterial strategy. Successful docking of Hemicholinium-3, a choline kinase inhibitor, to the model structure of P. aeruginosa ChoK also supports the use of this inhibitor or its derivatives to inhibit the growth of this microorganism. CONCLUSION: Therefore, the combination of the novel antimicrobial "choline kinase inhibitors (ChoKIs)" with a phage cocktail or synthetic phages as a potential treatment for P. aeruginosa infection has been proposed.

ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents.

Novel antimicrobial agents are crucial to combat antibiotic resistance in pathogenic bacteria. Choline kinase (ChoK) in bacteria catalyzes the synthesis of phosphorylcholine, which is subsequently incorporated into the cell wall or outer membrane. In certain species of bacteria, phosphorylcholine is also used to synthesize membrane phosphatidylcholine. Numerous human ChoK inhibitors (ChoKIs) have been synthesized and tested for anticancer properties. Inhibition of S. pneumoniae ChoK by human ChoKIs showed a promising effect by distorting the cell wall and retarded the growth of this pathogen. Comparison of amino acid sequences at the catalytic sites of putative choline kinases from pathogenic bacteria and human enzymes revealed striking sequence conservation that supports the potential application of currently available ChoKIs for inhibiting bacterial enzymes. We also propose the combined use of ChoKIs and nanoparticles for targeted delivery to the pathogen while shielding the human host from any possible side effects of the inhibitors. More research should focus on the verification of putative bacterial ChoK activities and the characterization of ChoKIs with active enzymes. In conclusion, the presence of ChoK in a wide range of pathogenic bacteria and the distinct function of this enzyme has made it an attractive drug target. This review highlighted the possibility of "choking" bacterial ChoKs by using human ChoKIs.