A Defective Viral Particle Approach to COVID-19

Abstract

The novel coronavirus SARS-CoV-2 has caused a pandemic resulting in millions of deaths worldwide. While multiple vaccines have been developed, insufficient vaccination combined with adaptive mutations create uncertainty for the future. Here, we discuss novel strategies to control COVID-19 relying on Defective Interfering Particles (DIPs) and related particles that arise naturally during an infection. Our intention is to encourage and to provide the basis for the implementation of such strategies by multi-disciplinary teams. We therefore provide an overview of SARS-CoV-2 for a multi-disciplinary readership that is specifically tailored to these strategies, we identify potential targets based on the current knowledge of the properties and functions of coronaviruses, and we propose specific strategies to engineer DIPs and other interfering or therapeutic nanoparticles.

Keywords: COVID-19; antivirus; aptamer; coronavirus; defective interfering particle; extracellular vesicle; immunity; synthetic defective viral genome; therapy.

Figure 1

Harnessing EV properties to combat SARS-CoV-2 infection or treat COVID-19. (A) EVs can be used to deliver nucleic acid sequences that either modulate the expression of specific targets, express genes of interests, or encode for viral products. (B) EVs can be used to deliver compounds of interest. (C) EVs derived from a specific cell type or tissue could be used to mitigate disease and trigger tissue regeneration. (D) EVs carrying the spike protein can be used to antagonize viral entry into a host cell. (E) EVs carrying the virus entry receptor ACE2 could serve as decoys for the virus. (F) EVs carrying viral antigens could be used for vaccine development. The image was generated with BioRender.com (accessed on 13 September 2021).

Figure 2

The SARS-CoV-2 genome. On entry into the host cell, a coronavirus particle is uncoated, and its single-stranded positive-sense RNA genome enters the cytoplasm. Two-thirds of the coronavirus genome is occupied by two large overlapping open reading frames (ORF1a and ORF1b) that are translated into polyproteins and that are processed to generate 16 non-structural proteins (nsp1 to nsp16). The rest of the genome includes ORFs for the structural proteins and several accessory proteins. The 5′-UTR is 265 nucleotides long, while the 3′-UTR is 358 nucleotides. The major distinction between other coronaviruses related to SARS-CoV and SARS-CoV-2 is in orf3b, Spike and orf8 but especially in the highly variable Spike S1 and orf8, which are recombination hot spots.