COVID-19 infection and nanomedicine applications for development of vaccines and therapeutics: An overview and future perspectives based on polymersomes

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection.

Keywords: 2019-nCoV; Coronavirus; Cytokine storm; Nanomedicine; SARS-CoV-2.

Fig. 1

COVID-19 symptoms according to WHO classification (WHO, 2020a).

Fig. 2

Schematic mechanism of replication of SARS-CoV-2 in a host cell. S protein on the surface of SARS-CoV-2 recognizes the ACE2 receptor on the cellular membrane of the host cell. The conformational changes at the S1 and S2 subunits facilitate the virus-cell fusion via endosomal pathway. The viral genome is released into the cytoplasm and translated through ribosomal frame shifting to generate replicas of polyproteins pp1a and pp1b. Following the genomic and sub-genomic synthesis, the viral proteins and the genomic RNA are inserted into virions and assembled in the ER-Golgi intermediate compartment (ERGIC) and then transported in the vesicles to the plasma membrane before being released out via exocytosis (Al-Hatamleh et al., 2020).

Fig. 3

Potential nanomedicine-based approaches for therapeutic and vaccine formulation against COVID-19.

Fig. 4

Commercial lipids used to encapsulate mRNA-1273 vaccine candidate from Moderna Inc.

Fig. 5

Amphiphilic block copolymers used to formulate polymersomes.

Fig. 6

Potential cellular and molecular mechanism of actions of polymersomes loaded with IL-6 receptor (IL-6R) blockers and DNA demethylation inhibitors against COVID-19 infection. Polymersomes will be synthesized, loaded with IL-6 receptor blockers and DNA demethylation inhibitors, and then functionalized with specific ligands to target cells expressing IL-6. IL-6 receptor blockers (e.g., a monoclonal antibody-based drug) would block the IL-6 receptor signaling pathway, while demethylation inhibitors might lead to epigenetic alteration, resulting in decreased expression of IL-6 receptor gene, thus downregulating IL-6 receptor in the targeted cell. Therefore, co-administration of these two therapeutics might cause effective synergistic effects to calm down the cytokine storm, which results mainly from the interaction of IL-6 and its receptor. The ADAMs (A disintegrin and metalloproteinases) are a family of transmembrane proteins that responsible for cleaving membrane-bound IL-6 receptor, resulting in soluble IL-6 receptor. Glycoprotein 130 (gp130) is a receptor for IL-6/sIL-6 receptor complex.