Abstract
Currently, the COVID-19 pandemic is an international challenge, largely due to lack of effective therapies. Pharmacotherapy has not yet been able to find a definitive treatment for COVID-19. Since SARS-CoV-2 affects several organs, treatment strategies that target the virus in a wider range are expected to be ultimately more successful. To this end, a two-step treatment strategy has been presented. In the first phase of the disease, when the patient is newly infected with the virus and the cytokine storm has not yet been developed, a chimeric peptide is used to inhibit virus entry into the host cell cytosol (by inhibiting endosomal pH acidification) and viral replication. After the virus entry and decrease of angiotensin converting enzyme 2 (ACE2) level, some people are unable to properly compensate for the ACE2 pathway and progress toward the cytokine storm. In the beginning of the cytokine storm, sACE2 protein is very effective in regulating the immune system toward the anti-inflammatory pathway, including M2 macrophages. Hence, the genes of 8P9R chimeric peptide and sACE2 would be inserted in an episomal vector with a separate promoter for each gene: the chimeric peptide gene promoter is a CMV promoter, while the sACE2 gene promoter is a NF-κB-sensitive promoter. The NF-κB-sensitive promoter induces the expression of sACE2 gene soon after elevation of NF-κB which is the main transcription factor of inflammatory genes. Thus, as the expression of inflammatory cytokines increases, the expression of sACE2 increases simultaneously. In this condition, sACE2 can prevent the cytokine storm by inhibiting the pro-inflammatory pathways. To deliver the designed vector to the target cells, mesenchymal stem cell-derived (MSC-derived) exosome-liposome hybrids are used. Herein, the strategy can be considered as a personalized clinical therapy for COVID-19, that can prevent morbidity and mortality in the future.
Highlights
Acute respiratory disease caused by COVID-19 has become a public health emergency and is a major health problem causing respiratory tract infection which can range from an asymptomatic form to severe acute respiratory distress syndrome (ARDS)
After treating with vectorcontaining exosome-liposome hybrids, the viral load could be measured by VNT assay and cellular viability will be measured by TUNNEL assay
After more than a year from the rise of COVID-19, several antiviral drugs and other pharmaceutical agents have been investigated as potential therapeutic candidates, but shockingly, most of them had been failed during clinical trials and yet supportive treatment strategies are the foremost critical portion of administration in serious cases of COVID-19 (CDC, 2021)
Summary
Acute respiratory disease caused by COVID-19 has become a public health emergency and is a major health problem causing respiratory tract infection which can range from an asymptomatic form to severe acute respiratory distress syndrome (ARDS). ARDS is one of the most common complications and the major cause of respiratory failure in severe COVID-19 patients. 33% of hospitalized COVID-19 patients develop ARDS. The mortality rate in COVID-19-associated ARDS is 45%, and the prevalence of ARDS in patients who died from COVID-19 is about 90% (Tzotzos et al, 2020). COVID19 can lead to multi-organ dysfunction and failure in severe cases. The therapeutic strategies are mainly based on supportive care and non-specific antiviral drugs. Due to its devastating consequences, it is essential to identify a potential therapeutic option to prevent and repair the destruction caused by the disease
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have