A DNA intercalating dye-based RT-qPCR alternative to diagnose SARS-CoV-2

RNA Biol. 2021 Dec;18(12):2218-2225. doi: 10.1080/15476286.2021.1926648. Epub 2021 May 26.

Abstract

Early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proven crucial during the efforts to mitigate the effects of the COVID-19 pandemic. Several diagnostic methods have emerged in the past few months, each with different shortcomings and limitations. The current gold standard, RT-qPCR using fluorescent probes, relies on demanding equipment requirements plus the high costs of the probes and specific reaction mixes. To broaden the possibilities of reagents and thermocyclers that could be allocated towards this task, we have optimized an alternative strategy for RT-qPCR diagnosis. This is based on a widely used DNA-intercalating dye and can be implemented with several different qPCR reagents and instruments. Remarkably, the proposed qPCR method performs similarly to the broadly used TaqMan-based detection, in terms of specificity and sensitivity, thus representing a reliable tool. We think that, through enabling the use of vast range of thermocycler models and laboratory facilities for SARS-CoV-2 diagnosis, the alternative proposed here can increase dramatically the testing capability, especially in countries with limited access to costly technology and reagents.

Keywords: COVID-19; RNA; RT-qPCR; RdRP; SARS-CoV-2; SYBR Green; TaqMan; diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzothiazoles / chemistry*
  • COVID-19 / diagnosis*
  • COVID-19 / virology
  • COVID-19 Nucleic Acid Testing / methods*
  • COVID-19 Nucleic Acid Testing / standards
  • DNA / analysis
  • DNA / biosynthesis
  • DNA Primers / chemistry
  • DNA Primers / metabolism
  • Diamines / chemistry*
  • Humans
  • Intercalating Agents / chemistry*
  • Nasopharynx / virology
  • Quinolines / chemistry*
  • RNA, Viral / genetics*
  • Real-Time Polymerase Chain Reaction / methods*
  • Real-Time Polymerase Chain Reaction / standards
  • SARS-CoV-2 / genetics*
  • Sensitivity and Specificity

Substances

  • Benzothiazoles
  • DNA Primers
  • Diamines
  • Intercalating Agents
  • Quinolines
  • RNA, Viral
  • SYBR Green I
  • DNA

Grants and funding

This work was supported by the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT, grant IP-COVID-19 429 to ARK) and by Fondos del Presupuesto del Servicio de Virosis Respiratorias, INEI-ANLIS Malbrán (EB). FFW is an ANPCYT fellow; JCM, JNS, LB, NNM, MP, LS and GC are fellows from Consejo Nacional de Investigaciones Científicas yTécnicas de Argentina (CONICET); JC and VB are support staff for research and development (CPA) from CONICET; MAGH, FRL, CCG, ARK, AS, MdlM, MJM, IES and EP are career investigators from CONICET.