RESUMEN
COVID-19 caused by SARS-CoV-2 is the latest pandemic which has thrown the world into an unprecedented social and economic uncertainties along with huge loss to humanity. Identification of the host factors regulating the replication of SARS-CoV-2 in human host may help in the development of novel anti-viral therapies to combat the viral infection and spread. Recently, some research groups used genome-wide CRISPR/Cas screening to identify the host factors critical for the SARS-CoV-2 replication and infection. A comparative analysis of these significant host factors (p < 0.05) identified fifteen proteins common in these studies. Apart from ACE2 (receptor for SARS-CoV-2 attachment), other common host factors were CSNK2B, GDI2, SLC35B2, DDX51, VPS26A, ARPP-19, C1QTNF7, ALG6, LIMA1, COG3, COG8, BCOR, LRRN2 and TLR9. Additionally, viral interactome of these host factors revealed that many of them were associated with several SARS-CoV-2 proteins as well. Interestingly, some of these host factors have already been shown to be critical for the pathogenesis of other viruses suggesting their crucial role in virus-host interactions. Here, we review the functions of these host factors and their role in other diseases with special emphasis on viral diseases.
Asunto(s)
COVID-19/virología , Interacciones Microbiota-Huesped , Factores Celulares Derivados del Huésped/metabolismo , Pandemias , SARS-CoV-2/fisiología , COVID-19/epidemiología , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Factores Celulares Derivados del Huésped/genética , Humanos , SARS-CoV-2/genéticaAsunto(s)
COVID-19 , Canalopatías , Canales Iónicos/metabolismo , Síndrome de QT Prolongado , Células Musculares , SARS-CoV-2 , COVID-19/complicaciones , COVID-19/metabolismo , COVID-19/fisiopatología , Canalopatías/metabolismo , Canalopatías/fisiopatología , Canalopatías/prevención & control , Canalopatías/virología , Sistema de Conducción Cardíaco/metabolismo , Sistema de Conducción Cardíaco/virología , Interacciones Microbiota-Huesped , Factores Celulares Derivados del Huésped/metabolismo , Humanos , Síndrome de QT Prolongado/etiología , Síndrome de QT Prolongado/metabolismo , Síndrome de QT Prolongado/prevención & control , Síndrome de QT Prolongado/virología , Células Musculares/fisiología , Células Musculares/virología , SARS-CoV-2/patogenicidad , SARS-CoV-2/fisiologíaRESUMEN
Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).