CRISPR Cas13: a potential therapeutic option of COVID-19

CRISPR Cas13: a potential therapeutic option of COVID-19
Melika Lotfi,^1,*
1. Zanjan University of Medical sciences
Introduction: The novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be considered as the most important current global issue, as it has caused the novel coronavirus disease (COVID-19) pandemic, which has resulted in high mortality and morbidity rates all around the world. Although scientists are trying to discover novel therapies and develop and evaluate various previous treatments, at the time of writing this paper, there was no definite therapy and vaccine for COVID-19. So, as COVID-19 has called ideas for treatment, controlling, and diagnosis, we decided to present our hypothesis, which has received less attention, about treating COVID-19 through CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Cas13.
Methods: searching online on google scholar, PubMed, and Scopus based on the keywords including COVID-19, CRISPR Cas13, SARS-CoV-2, genome, and treatment.
Results: COVID-19 outbreak, accompanying numerous of pneumonia cases caused by SARS-CoV-2, emerged in Wuhan, a city in the Hubei province of China, late 2019. Although it was indicated that the patients infected with SARS-CoV-2 (formerly named 2019-nCoV ) in China might have used (as a source of food) or encountered infected animals in the seafood market, more inquiry displayed some patients with no record of visiting the seafood market. So, the person-to-person contagion of the virus through coughing, sneezing, aerosols that could infiltrate to lungs via nose or mouth is inevitable. There are seven coronaviruses that caused disease in humans. Two strains with zoonotic origination containing Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) were connected to the emergence of severe respiratory diseases in humans in 2003 and 2012 subsequently, and now, SARS-COV-2 as the seventh virus of the coronavirus family has caused severe respiratory diseases pandemic in humans. As it is severely contagious, there is a rapid progression in morbidity and mortality rates of COVID-19, and there is no certain vaccine and treatment for that, the best solution for controlling the pandemic in addition to following preventive methods can be suggesting and finding probable effective therapies. In this paper, we have suggested CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Cas13 as a potential therapy, in various aspects, of COVID-19. Clinical manifestations Clinical manifestations are variable based on various reasons. Although the primary symptoms of COVID-19 are prevalently identified as cough, fever, shortness of breath, in another investigation, confusion, chest pain, nausea, and vomiting were the most prominent COVID-19 symptoms and coma was reported in one study. Not only the American Academy of Otolaryngology has reported the loss of sense of smell and taste disorder (anosmia and dyspepsia) in some COVID-19 patients, but also they were even the unique signs in some of them. It must be noticed that viral conjunctivitis must be regarded as a probable early manifestation of COVID-19. Besides, SARS-CoV-2 can cause acute kidney failure and involve the cardiovascular system and the Gastrointestinal system. 2019-nCoV features Although the viral genome analysis revealed that SARS-CoV-2 (formerly named 2019-nCoV) is 88% similar to bat-SL-CoVZC45, bat-SL-CoVZXC21 and 96.2% identical to a bat CoV RaTG13, recent studies proposed Malaysian smuggled pangolins to China, along with some probable alternative intermediate hosts like turtles and snacks as the probabilistic provenance of the virus. Moreover, the most genomic encoded proteins of SARS-CoV-2 are 79.5% and 51% identical to SARS-CoV and MERS-CoV respectively, and resembling SARS-CoV it uses ACE2 receptor for cellular entry which the high virus affinity to the ACE2 receptor is perhaps due to natural selection rather than premeditated manipulation. Coronavirus spike (S) protein has been ascertained as a substantial determinative of virus entry into host cells as the receptor-binding domain (RBD) for binding to ACE2 receptor, and direct membrane fusion between the virus and plasma membrane has been placed on the head of that. Furthermore, alongside the membrane fusion, the clathrin-dependent and -independent endocytosis mediates the SARS-CoV entry. After admittance, the viral RNA genome is liberated into the cytoplasm and is translated into two polyproteins and structural proteins, after which the viral genome begins replication. The newly formed envelope glycoproteins are intromitted into the membrane of the endoplasmic reticulum or Golgi, and the nucleocapsid is composed via compounding the genomic RNA and nucleocapsid protein. Afterward, viral particles bud into the endoplasmic reticulum-Golgi mediator compartment (ERGIC). Eventually, for releasing the virus out of the infected cell, the vesicles containing the virus particles fuse to the plasma membrane. Novel coronavirus or 2019-nCoV is an enveloped, positive-sense, and single-stranded RNA beta-coronavirus, which is about 29.9 kb with a cap structure at its 5′ end and a poly-A tail at the 3′ end. Like other coronaviruses, it has particular viral replicase genes in a variable number (6–14) open reading frame (ORF), which codifies vital proteins (27-29 ones) for viral replication, nucleocapsid, and spikes formation. Two-thirds of viral RNA, principally placed in the 5′-terminal in the first ORF (ORF1a/b) translates two polyproteins, pp1a and pp1b, which codifies 16 non-structural proteins (NSP), whereas the rest of ORFs encode at least 8 accessory proteins (ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF9a, ORF9b, and ORF10) intervening with the host innate immune response. It must be mentioned that there are intra-viral protein-protein intercommunications between most of these proteins, which make the situation more complicated than before.
Conclusion: In conclusion, among various potential therapeutic options of COVID-19, CRISPR Cas13 has been omitted. However, it has the potential to be successful against SARS-CoV-2.
Keywords: CRISPR Cas13, SARS-CoV-2, genome, and treatment.