Virus World

The COVID-19 pandemic has claimed the lives of more than one million people worldwide. The causative agent, SARS-CoV-2, is a member of the Coronaviridae family, which are viruses that cause respiratory infections of varying severity. The cellular host factors and pathways co-opted by SARS-CoV-2 and other coronaviruses in the execution of their life cycles remain ill-defined. To develop an extensive compendium of host factors required for infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E), we performed parallel genome-scale CRISPR knockout screens.

These screens uncovered multiple host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, and glycosylphosphatidylinositol biosynthesis, as well as an unexpected requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and all other coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus spillover events.

Preprint available in bioRxiv (October 8, 2020):

https://doi.org/10.1101/2020.10.07.326462

The kit has been granted approval under ‘emergency use’ provisions, and should help to ease testing backlogs in the country. The US drug regulator has granted its first emergency-use approval for a new coronavirus test that takes advantage of the gene-editing technology CRISPR. 

The US Food and Drug Administration’s (FDA) emergency-use authority allows it to make tests and drugs available faster than usual in a public-health emergency. The new diagnostic kit is based on an approach co-developed by CRISPR pioneer Feng Zhang at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. It will be used to test for the novel coronavirus behind the ongoing pandemic, SARS-CoV-2, in laboratories that are certified to provide clinical-test results. Although the United States has ramped up testing in the past week — averaging nearly 250,000 tests per day, according to the non-profit organization The COVID Tracking Project — there are test shortages in some places. Widespread use of the new FDA-approved kit could help to alleviate backlogs and increase testing, says Mitchell O’Connell, a biochemist at the University of Rochester in New York, who was not involved in developing the test. But O’Connell cautions that it remains to be seen how well the test performs in real-world conditions, such as hospitals, compared with standard tests.

The CRISPR-based diagnostic kit has been developed by Sherlock Biosciences, a biotechnology company also based in Cambridge. It works by programming the CRISPR machinery, which has the ability to home in on certain genetic sequences, to detect a snippet of SARS-CoV-2 genetic material in a nose, mouth or throat swab, or in fluid from the lungs. If the virus’s genetic material is found, a CRISPR enzyme generates a fluorescent glow. The test can return results in about an hour, according to the company....