CRISPR-Cas System: An Approach With Potentials for COVID-19 Diagnosis and Therapeutics.

Prashant Kumar,Balasubramanian Ganesh,Senthilkumar Natesan,Mohd Iqbal Yatoo,Yashpal Singh Malik,Somnath Rahangdale,Sharad Saurabh,Ashish Srivastava,Ruchi Tiwari,Kuldeep Dhama,Khan Sharun,Raj Kumar Singh

doi:10.3389/fcimb.2020.576875

Abstract

COVID-19, the human coronavirus disease caused by SARS-CoV-2, was reported for the first time in Wuhan, China in late 2019. COVID-19 has no preventive vaccine or proven standard pharmacological treatment, and consequently, the outbreak swiftly became a pandemic affecting more than 215 countries around the world. For the diagnosis of COVID-19, the only reliable diagnostics is a qPCR assay. Among other diagnostic tools, the CRISPR-Cas system is being investigated for rapid and specific diagnosis of COVID-19. The CRISPR-Cas-based methods diagnose the SARS-CoV-2 infections within an hour. Apart from its diagnostic ability, CRISPR-Cas system is also being assessed for antiviral therapy development; however, till date, no CRISPR-based therapy has been approved for human use. The Prophylactic Antiviral CRISPR in huMAN cells (PAC-MAN), which is Cas 13 based strategy, has been developed against coronavirus. Although this strategy has the potential to be developed as a therapeutic modality, it may face significant challenges for approval in human clinical trials. This review is focused on describing potential use and challenges of CRISPR-Cas based approaches for the development of rapid and accurate diagnostic technique and/or a possible therapeutic alternative for combating COVID-19. The assessment of potential risks associated with use of CRISPR will be important for future clinical advancements.

Highlights

Coronaviruses (CoVs), derived from the Latin word corona, are a group of viruses that have crown-like spikes on their outer surface (Rabi et al, 2020)
The virus causing COVID-19 resembles severe acute respiratory syndrome coronavirus (SARS-CoV), it was termed SARS-CoV-2 by the International Committee on Taxonomy of Viruses (ICTV)
The transcription of CRISPR array occurs in expression processing stage to produce a single long precrRNA which is processed by a distinct set of Cas proteins to generate mature CRISPR RNA (crRNA) (Charpentier et al, 2015; Hochstrasser and Doudna, 2015)

Summary

INTRODUCTION

Coronaviruses (CoVs), derived from the Latin word corona (crown), are a group of viruses that have crown-like spikes on their outer surface (Rabi et al, 2020). CRISPR-Cas system has been identified as a part of adaptive immune system in archaea and bacteria against the virus infections (Brouns et al, 2008) and its applications in humans were found later (Jinek et al, 2012) This system is a promising tool to develop novel diagnostics and for development of therapeutics to eliminate viral infections (Bayat et al, 2018; Jia et al, 2020). The transcription of CRISPR array occurs in expression processing stage to produce a single long precrRNA which is processed by a distinct set of Cas proteins to generate mature crRNA (Charpentier et al, 2015; Hochstrasser and Doudna, 2015) This is followed by the interference stage wherein the mature crRNA, bound to the processing complex, acts as guide RNA to recognize similar sequences in the invading viral RNA that is cleaved and inactivated by one of the Cas proteins (Figure 1; Table 1) (Plagens et al, 2015; Nishiyama et al, 2017; Nishiyama, 2019).

Cas2 3 Cas3 4 Cas4 5 Cas5 6 Cas6 7 Cas7 8 Cas8 9 Cas9

LIMITATIONS

Findings

CONCLUSION AND FUTURE PROSPECTS