Suppression of Human Coronavirus 229E Infection in Lung Fibroblast Cells via RNA Interference

Abstract

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will result in lower viral load and reduced cell death. Two different categories of nucleic acid delivery systems, Peptide/Lipid-Associated Nucleic Acids (PLANAs) and lipophilic polymers, were investigated for their toxicity in human lung fibroblast cells and their ability to deliver specific siRNAs targeting Spike and Envelope proteins in order to prevent cell death in infected cells. Selected siRNAs were effectively delivered to human lung fibroblast cells with negligible toxicity. Cell death due to viral infection was significantly reduced with individual and combinatorial silencing of selected viral proteins. The combinatorial silencing of Spike and Envelope proteins restored the cell viability completely and eliminated plaques in the investigated system. Our cell culture data indicate promising results for the RNAi based approach as an alternative antiviral treatment.

Antiviral Activity of the Rhamnolipids Mixture from the Antarctic Bacterium Pseudomonas gessardii M15 against Herpes Simplex Viruses and Coronaviruses

“…The antiviral activity of the M15RL mixture produced by P. gessardii M15 was first investigated against HSV-1 and HCoV-229E in both co-treatment and virus pre-treatment experiments through the quantification of plaques reduction. HSV-1 and 229E were chosen to represent a viral model for enveloped DNA and RNA viruses, respectively [45,46]. In the co-treatment experiment, Vero cells were treated simultaneously with viruses and M15RL at different concentrations.…”

Potential of siRNA in COVID-19 therapy: Emphasis on in silico design and nanoparticles based delivery

“…The polymer siRNA complex showed more than 85% cell viability, and their transfection efficiency was similar to reference Lipofectamine ™ (Montazeri Aliabadi et al, 2021). Further, biodegradable cationic polymers with ester bonds, such as poly (beta-amino ester), are used for siRNA delivery as they offer effective endosomal escape, flexible Frontiers in Bioengineering and Biotechnology frontiersin.org conjugate binding capabilities, high stability, and tunable charge density (Nezhad, 2022).…”

“…Also, the lipophilic PEIs was used for carrying the siRNA for the toxicity studies on human lung fibroblast cells and delivery of siRNA against Human Coronavirus 229E. The polymer siRNA complex showed more than 85% cell viability, and their transfection efficiency was similar to reference Lipofectamine™ ( Montazeri Aliabadi et al, 2021 ). Further, biodegradable cationic polymers with ester bonds, such as poly (beta-amino ester), are used for siRNA delivery as they offer effective endosomal escape, flexible conjugate binding capabilities, high stability, and tunable charge density ( Nezhad, 2022 ).…”

Ginkgolic Acid Inhibits Coronavirus Strain 229E Infection of Human Epithelial Lung Cells

“…Although current evidence indicates that the immune response generated by the available vaccines is robust for certain SARS-CoV-2 variants, the effectiveness of long-term immunity remains to be determined. Moreover, vaccine hesitancy and lack of vaccine availability aid in the global dissemination of SARS-CoV-2; hence, there is a growing need for therapeutic agents to mitigate the pathogenesis of the rapidly mutating variants, thereby minimizing morbidity and mortality [9].…”