Loss of Detection of sgN Precedes Viral Abridged Replication in COVID-19-Affected Patients-A Target for SARS-CoV-2 Propagation

Int J Mol Sci. 2022 Feb 9;23(4):1941. doi: 10.3390/ijms23041941.

Abstract

The development of prophylactic agents against the SARS-CoV-2 virus is a public health priority in the search for new surrogate markers of active virus replication. Early detection markers are needed to follow disease progression and foresee patient negativization. Subgenomic RNA transcripts (with a focus on sgN) were evaluated in oro/nasopharyngeal swabs from COVID-19-affected patients with an analysis of 315 positive samples using qPCR technology. Cut-off Cq values for sgN (Cq < 33.15) and sgE (Cq < 34.06) showed correlations to high viral loads. The specific loss of sgN in home-isolated and hospitalized COVID-19-positive patients indicated negativization of patient condition, 3-7 days from the first swab, respectively. A new detection kit for sgN, gene E, gene ORF1ab, and gene RNAse P was developed recently. In addition, in vitro studies have shown that 2'-O-methyl antisense RNA (related to the sgN sequence) can impair SARS-CoV-2 N protein synthesis, viral replication, and syncytia formation in human cells (i.e., HEK-293T cells overexpressing ACE2) upon infection with VOC Alpha (B.1.1.7)-SARS-CoV-2 variant, defining the use that this procedure might have for future therapeutic actions against SARS-CoV-2.

Keywords: 2′-O-methyl antisense RNA; SARS-CoV-2 virus particles; qPCR methods; sgE; sgN.

MeSH terms

  • COVID-19 / virology*
  • Coronavirus Nucleocapsid Proteins / analysis
  • Coronavirus Nucleocapsid Proteins / genetics*
  • Giant Cells / drug effects
  • Giant Cells / virology
  • HEK293 Cells
  • Humans
  • Limit of Detection
  • Nasopharynx / virology
  • Phosphoproteins / analysis
  • Phosphoproteins / genetics
  • RNA, Antisense / pharmacology
  • RNA, Viral
  • Ribonuclease P / genetics
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology*
  • Sensitivity and Specificity
  • Social Isolation
  • Viral Load
  • Viroporin Proteins / genetics
  • Virus Replication / drug effects
  • Virus Replication / physiology*

Substances

  • Coronavirus Nucleocapsid Proteins
  • E protein, SARS coronavirus
  • Phosphoproteins
  • RNA, Antisense
  • RNA, Viral
  • Viroporin Proteins
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • Ribonuclease P