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HGNC Genes

SARS-CoV-2 proteins

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    Multiple Sites on SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD Protein are Susceptible to Proteolysis by Cathepsins B, K, L, S, and V

    Authors: Keval Bollavaram; Tiffanie Leeman; Akhil Kulkarni; Sophia Upshaw; Maggie Lee; Jiabei Yang; Hannah Song; Manu O Platt

    doi:10.1101/2021.02.17.431617 Date: 2021-02-17 Source: bioRxiv

    SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic MESHD. Proteases are central to the infection process of SARS-CoV-2 MESHD. Cleavage of the spike protein PROTEIN on the virus capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2 HGNC, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein PROTEIN must be identified. We identified amino acid sequences in all regions of spike protein PROTEIN, including the S1/S2 region critical for activation and viral entry, that are susceptible to cleavage by furin HGNC and cathepsins B, K, L, S, and V using PACMANS, a computational platform that identifies and ranks preferred sites of proteolytic cleavage on substrates, and verified with molecular docking analysis and immunoblotting to determine if binding of these proteases can occur on the spike protein PROTEIN that were identified as possible cleavage sites. Together, this study highlights cathepsins B, K, L, S, and V for consideration in SARS-CoV-2 infection MESHD and presents methodologies by which other proteases can be screened to determine a role in viral entry. This highlights additional proteases to be considered in COVID-19 MESHD studies, particularly regarding exacerbated damage in inflammatory preconditions where these proteases are generally upregulated.

    Fibrinolysis influences SARS-CoV-2 infection MESHD in ciliated cells

    Authors: Myoung Ryoul Park; Chunmei Cai; Min-Jung Seo; Hong-Tae Yun; Soo-Kwon Park; Man-Soo Choi; Chang-Hwan Park; Jung Kyung Moon

    doi:10.1101/2021.01.07.425801 Date: 2021-01-08 Source: bioRxiv

    Rapid spread of COVID-19 MESHD has caused an unprecedented pandemic worldwide, and an inserted furin HGNC site in SARS-CoV-2 spike PROTEIN protein (S PROTEIN) may account for increased transmissibility. Plasmin HGNC, and other host proteases, may cleave the furin HGNC site of SARS-CoV-2 S protein PROTEIN and {gamma} subunits of epithelial sodium channels ({gamma} ENaC), resulting in an increment in virus infectivity and channel activity. As for the importance of ENaC in the regulation of airway surface and alveolar fluid homeostasis MESHD, whether SARS-CoV-2 will share and strengthen the cleavage network with ENaC proteins at the single-cell level is urgently worthy of consideration. To address this issue, we analyzed single-cell RNA sequence (scRNA-seq) datasets, and found the PLAU HGNC (encoding urokinase plasminogen activator), SCNN1G HGNC ({gamma}ENaC), and ACE2 HGNC (SARS-CoV-2 receptor) were co-expressed in alveolar epithelial MESHD, basal, club, and ciliated epithelial cells. The relative expression level of PLAU HGNC, TMPRSS2 HGNC, and ACE2 HGNC were significantly upregulated in severe COVID-19 MESHD patients and SARS-CoV-2 infected MESHD cell lines using Seurat and DESeq2 R packages. Moreover, the increments in PLAU HGNC, FURIN HGNC, TMPRSS2 HGNC, and ACE2 HGNC were predominately observed in different epithelial cells and leukocytes. Accordingly, SARS-CoV-2 may share and strengthen the ENaC fibrinolytic proteases network in ACE2 HGNC positive airway and alveolar MESHD epithelial cells, which may expedite virus infusion into the susceptible cells and bring about ENaC associated edematous respiratory condition MESHD.

    Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration

    Authors: Jana Koch; Zina M Uckeley; Patricio Doldan; Megan L Stanifer; Steeve Boulant; Pierre-Yves Lozach

    doi:10.1101/2020.12.22.423906 Date: 2020-12-23 Source: bioRxiv

    SARS-CoV-2 is a newly emerged coronavirus (CoV) that spread through human populations worldwide in early 2020. CoVs rely on host cell proteases for activation and infection. The trypsin-like protease TMPRSS2 HGNC at the cell surface, cathepsin L HGNC in endolysosomes, and furin HGNC in the Golgi have all been implicated in the SARS-CoV-2 proteolytic processing. Whether SARS-CoV-2 depends on endocytosis internalization and vacuolar acidification for infectious entry remains unclear. Here, we examined the dynamics of SARS-CoV-2 activation during the cell entry process in tissue culture. Using four cell lines representative of lung, colon MESHD, and kidney epithelial tissues, we found that TMPRSS2 HGNC determines the SARS-CoV-2 entry pathways. In TMPRSS2 HGNC-positive cells, infection was sensitive to aprotinin, a TMPRSS2 HGNC inhibitor, but not to SB412515, a drug that impairs cathepsin L HGNC. Infectious penetration was marginally dependent on endosomal acidification, and the virus passed the protease-sensitive step within 10 min. In a marked contrast, in TMPRSS2 HGNC-negative cells cathepsin L HGNC and low pH were required for SARS-CoV-2 entry. The cathepsin L HGNC-activated penetration occurred within 40-60 min after internalization and required intact endolysosomal functions. Importantly, pre-activation of the virus allowed it to bypass the need for endosomal acidification for viral fusion and productive entry. Overall, our results indicate that SARS-CoV-2 shares with other CoVs a strategy of differential use of host cell proteases for activation and infectious penetration. This study also highlights the importance of TMPRSS2 HGNC in dictating the entry pathway used by SARS-CoV-2. SignificancePreventing SARS-CoV-2 spread requires approaches affecting early virus-host cell interactions before the virus enters and infects target cells. Host cell proteases are critical for coronavirus activation and infectious entry. Here, we reconcile apparent contradictory observations from recent reports on endosomal acidification and the role of furin HGNC, TMPRSS2 HGNC, and cathepsin L HGNC in the productive entry and fusion process of SARS-CoV-2. Investigating authentic virus in various cell types, we demonstrated that SARS-CoV-2 developed the ability to use different entry pathways, depending on the proteases expressed by the target cell. Our results have strong implications for future research on the apparent broad tropism of the virus in vivo. This study also provides a handle to develop novel antiviral strategies aiming to block virus entry, as illustrated with the several drugs that we identified to prevent SARS-CoV-2 infection MESHD, some with low IC50.

    Furin HGNC cleaves SARS-CoV-2 spike PROTEIN-glycoprotein at S1/S2 and S2'for viral fusion/entry: indirect role for TMPRSS2

    Authors: Rachid Essalmani; Jaspreet Jain; Delia Susan-Resiga; Ursula Andreo; Alexandra Evagelidis; Rabeb Mouna Derbali; David Huynh; Frederic Dallaire; Melanie Laporte; Adrien Delpal; Priscila Sutto-Ortiz; Bruno Coutard; Claudine Mapa; Keith Wilcoxen; Etienne Decroly; Tram Pham; Eric A. Cohen; Nabil G. G Seidah; Massimo Zollo; Achille Iolascon; Mario Capasso; Nour Albes; Hani M. Al-Afghani; Bader Alghamdi; Mansour Almutair; Ebrahim Sabri Mahmoud; Leen Abu Safie; Hadeel El Bardisy; Fawz S. Al Harthi; Abdulraheem Alshareef; Bandar Ali Suliman; Saleh Alqahtani; Abdulaziz AlMalik; May M. Alrashed; Salam Massadeh; Vincent Mooser; Mark Lathrop; Yaseen Arabi; Hamdi Mbarek; Chadi Saad; Wadha Al-Muftah; Radja Badji; Asma Al Thani; Said I. Ismail; Ali G. Gharavi; Malak S. Abedalthagafi; J Brent Richards; David B. Goldstein; Krzysztof Kiryluk

    doi:10.1101/2020.12.18.423106 Date: 2020-12-20 Source: bioRxiv

    The Spike (S)-protein PROTEIN of SARS-CoV-2 binds host-cell receptor ACE2 HGNC and requires proteolytic 'priming' (S1/S2) and 'fusion-activation' (S2') for viral entry. The S-protein PROTEIN furin HGNC-like motifs PRRAR685{downarrow} and KPSKR815{downarrow} indicated that proprotein convertases promote virus entry. We demonstrate that furin HGNC and PC5A induce cleavage at both sites, ACE2 HGNC enhances S2' processing, and their pharmacological inhibition (BOS-inhibitors) block endogenous cleavages. S1/S2-mutations (S1/S2) limit S-protein PROTEIN-mediated cell-to-cell fusion, similarly to BOS-inhibitors. Unexpectedly, TMPRSS2 HGNC does not cleave at S1/S2 or S2', but it can: (i) cleave/inactivate S-protein PROTEIN into S2a/S2b; (ii) shed ACE2 HGNC; (iii) cleave S1-subunit into secreted S1', activities inhibited by Camostat. In lung-derived Calu-3 cells, BOS-inhibitors and S1/S2 severely curtail 'pH-independent' viral entry, and BOS-inhibitors alone/with Camostat potently reduce infectious viral titer and cytopathic effects. Overall, our results show that: furin HGNC plays a critical role in generating fusion-competent S-protein PROTEIN, and indirectly, TMPRSS2 HGNC promotes viral entry, supporting furin HGNC and TMPRSS2 HGNC inhibitors as potential antivirals against SARS-CoV-2

    Genetic variability in COVID-19 MESHD-related genes in the Brazilian population

    Authors: Rodrigo Secolin; Tania K de Araujo; Marina C. Gonsales; Cristiane S. Rocha; Michel Satya Naslavsky; Luiz De Marco; Maria Bicalho; Vinicius L Vazquez; Mayana Zatz; Wilson A Silva Jr.; Iscia Lopes-Cendes; Sebla B Kutluay; Mei-Ling Li; Gary Brewer; Blanton S Tolbert; Amanda E Hargrove; Alexandra W. Dretler; Ria Gripaldo; Andrea N. Lane; Hao Wu; Saeyun Lee; Mindy Hernandez; Vanessa Engineer; John Varghese; Sang Le; Iñaki Sanz; John L. Daiss; Frances Eun-Hyung Lee

    doi:10.1101/2020.12.04.411736 Date: 2020-12-06 Source: bioRxiv

    SARS-CoV-2 employs the angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptor and the transmembrane serine protease ( TMPRSS2 HGNC) to infect human lung cells. Previous studies have suggested that different host genetic backgrounds in ACE2 HGNC and TMPRSS2 HGNC could contribute to differences in the rate of infection or severity of COVID-19 MESHD. Recent studies also showed that variants in 15 genes related to type I interferon immunity to influenza virus could predispose to life-threatening COVID-19 MESHD pneumonia MESHD. Additional genes ( SLC6A20 HGNC, LZTFL1 HGNC, CCR9 HGNC, FYCO1 HGNC, CXCR6 HGNC, XCR1 HGNC, IL6 HGNC, CTSL HGNC, ABO, and FURIN HGNC) and HLA alleles have also been implicated in response to infection with SARS-CoV-2. Currently, Brazil has recorded the third-highest number of COVID-19 MESHD patients worldwide. We aim to investigate the genetic variation present in COVID-19 MESHD-related genes in the Brazilian population. We analysed 27 candidate genes and HLA alleles in 954 admixed Brazilian exomes. We used the information available in two public databases (http://www.bipmed.org and http://abraom.ib.usp.br/), and additional exomes from individuals born in southeast Brazil, the region with the highest number of COVID-19 MESHD patients in the country. Variant allele frequencies were compared with the 1000 Genomes Project phase 3 (1KGP) and the gnomAD databases. We found 395 non-synonymous variants; of these, 325 were also found in the 1000 Genome Project phase 3 (1KGP) and/or gnomAD. Six of these variants were previously reported as putatively influencing the rate of infection or clinical prognosis for COVID-19 MESHD. The remaining 70 variants were identified exclusively in the Brazilian sample, with a mean allele frequency of 0.0025. In silico prediction of the impact in protein function revealed that three of these rare variants were pathogenic. Furthermore, we identified HLA alleles that were previously associated with COVID-19 MESHD response at loci DQB1 HGNC and DRB1 HGNC. Our results showed genetic variability common to other populations, but also rare and ultra-rare variants exclusively found in the Brazilian population. These findings could potentially lead to differences in the rate of infection or response to infection by SARS-CoV-2 and should be further investigated in patients with the disease.

    Multimodal Single-Cell Omics Analysis of COVID-19 MESHD Sex Differences in Human Immune Systems

    Authors: Yuan Hou; Yadi Zhou; Michaela Gack; Justin Lathia; Asha Kallianpur; Reena Mehra; Timothy Chan; Jae U. Jung; Lara Jehi; Charis Eng; Feixiong Cheng; Emily R Ko; Ephraim L Tsalik; gregory sempowski; Thomas N Denny; Thomas W Burke; Micah T McClain; Christopher W. Woods; Xiling Shen; Daniel R Saban; Brea Tinsley; Alan Trudeau; Jitendra Singh; Lindsey Whitmore; Helen Zheng; Matthew Benedek; Jenna Currier; Mark Dresel; Ashish Duvvuru; Britney Dyszel; Emily Fingar; Elizabeth M. Hennen; Michael Kirsch; Ali A. Khan; Charlotte Labrie-Cleary; Stephanie Laporte; Evan Lenkeit; Kailey Martin; Marilyn Orellana; Melanie Ortiz-Alvarez de la Campa; Isaac Paredes; Baleigh Wheeler; Allison Rupert; Andrew Sam; Katherine See; Santiago Soto Zapata; Paul A. Craig; Bonnie L. Hall; Jennifer Jiang; Julia R. Koeppe; Stephen A. Mills; Michael J. Pikaart; Rebecca Roberts; Yana Bromberg; J. Steen Hoyer; Siobain Duffy; Jay Tischfield; Francesc X. Ruiz; Eddy Arnold; Jean Baum; Jesse Sandberg; Grace Brannigan; Sagar D. Khare; Stephen K. Burley

    doi:10.1101/2020.12.01.407007 Date: 2020-12-01 Source: bioRxiv

    Sex differences in the risk of SARS-CoV-2 infection MESHD have been controversial and the underlying mechanisms of COVID-19 MESHD sexual dimorphism remain understudied. Here we inspected sex differences in SARS-CoV-2 positivity, hospitalization, admission to the intensive care unit (ICU), sera immune profiling, and two single-cell RNA-sequencing (snRNA-seq) profiles from nasal tissues and peripheral blood mononuclear cells (PBMCs) of COVID-19 MESHD patients with varying degrees of disease severity. Our propensity score-matching observations revealed that male individuals have a 29% increased likelihood of SARS-CoV-2 positivity, with a hazard ration (HR) 1.32 (95% confidence interval [CI] 1.18-1.48) for hospitalization and HR 1.51 (95% CI 1.24-1.84) for admission to ICU. Sera from male patients at hospital admission had decreased lymphocyte count and elevated inflammatory markers ( C-reactive protein HGNC, procalcitonin, and neutrophils). We found that SARS-CoV-2 entry factors, including ACE2 HGNC, TMPRSS2 HGNC, FURIN HGNC and NRP1 HGNC, have elevated expression in nasal squamous MESHD cells from males with moderate and severe COVID-19 MESHD. Cell-cell network proximity analysis suggests possible epithelium-immune cell interactions and immune vulnerability underlying a higher mortality in males with COVID-19 MESHD. Monocyte-elevated expression of Toll like receptor 7 HGNC ( TLR7 HGNC) and Bruton tyrosine kinase ( BTK HGNC) is associated with severe outcomes in males with COVID-19 MESHD. These findings provide basis for understanding immune responses underlying sex differences, and designing sex-specific targeted treatments and patient care for COVID-19 MESHD.

    A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro

    Authors: Mary Hongying Cheng; Rebecca A. Porritt; Magali Noval Rivas; James Krieger; Asli Beyza Ozdemir; Gustavo Garcia Jr.; Vaithilingaraja Arumugaswami; Bettina C. Fries; Moshe Arditi; Ivet Bahar; Jinan Suliman; Elias Tayar; Hasan Ali Kasem; Meynard J. A. Agsalog; Bassam K. Akkarathodiyil; Ayat A. Alkhalaf; Mohamed Morhaf M. H. Alakshar; Abdulsalam Ali A. H. Al-Qahtani; Monther H. A. Al-Shedifat; Anas Ansari; Ahmad Ali Ataalla; Sandeep Chougule; Abhilash K. K. V. Gopinathan; Feroz J. Poolakundan; Sanjay U. Ranbhise; Saed M. A. Saefan; Mohamed M. Thaivalappil; Abubacker S. Thoyalil; Inayath M. Umar; Zaina Al Kanaani; Abdullatif Al Khal; Einas Al Kuwari; Adeel A. Butt; Peter Coyle; Andrew Jeremijenko; Anvar Hassan Kaleeckal; Ali Nizar Latif; Riyazuddin Mohammad Shaik; Hanan F. Abdul Rahim; Hadi M. Yassine; Gheyath K. Nasrallah; Mohamed G. Al Kuwari; Odette Chaghoury; Hiam Chemaitelly; Laith J Abu-Raddad

    doi:10.1101/2020.11.24.395079 Date: 2020-11-24 Source: bioRxiv

    We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B MESHD ( SEB MESHD SEB HGNC), near the S1/S2 cleavage site of SARS-CoV-2 Spike PROTEIN protein, which might explain the multisystem-inflammatory syndrome MESHD ( MIS-C MESHD MIS-C HGNC) observed in children and cytokine storm in severe COVID-19 MESHD patients. We show here that an anti- SEB MESHD SEB HGNC monoclonal antibody (mAb), 6D3, can bind this viral motif, and in particular its PRRA insert, to inhibit infection by blocking the access of host cell proteases, TMPRSS2 HGNC or furin HGNC, to the cleavage site. The high affinity of 6D3 for the furin HGNC-cleavage site originates from a poly-acidic segment at its heavy chain CDR2 HGNC, a feature shared with SARS-CoV-2-neutralizing mAb 4A8. The affinity of 6D3 and 4A8 for this site points to their potential utility as therapeutics for treating COVID-19 MESHD, MIS HGNC-C, or common cold caused by human coronaviruses (HCoVs) that possess a furin HGNC-like cleavage site.

    The furin HGNC cleavage site of SARS-CoV-2 spike PROTEIN protein is a key determinant for transmission due to enhanced replication in airway cells.

    Authors: Thomas P. Peacock; Daniel H. Goldhill; Jie Zhou; Laury Baillon; Rebecca Frise; Olivia C. Swann; Ruthiran Kugathasan; Rebecca Penn; Jonathan C. Brown; Raul Y. Sanchez-David; Maia Kavanagh Williamson; Jack A. Hassard; Ecco Staller; Brian Hanley; Michael Osborn; Andrew D. Davidson; Wendy S. Barclay; Mohammad Mohiuddin; Naznin Sultana; Kakon Nag

    doi:10.1101/2020.09.30.318311 Date: 2020-09-30 Source: bioRxiv

    SARS-CoV-2 enters cells via its spike glycoprotein PROTEIN which must be cleaved sequentially at the S1/S2, then the S2' cleavage sites (CS) to mediate membrane fusion. SARS-CoV-2 has a unique polybasic insertion at the S1/S2 CS HGNC, which we demonstrate can be cleaved by furin HGNC. Using lentiviral pseudotypes and a cell-culture adapted SARS-CoV-2 virus with a S1/S2 deletion, we show that the polybasic insertion is selected for in lung cells and primary human airway epithelial cultures but selected against in Vero E6, a cell line used for passaging SARS-CoV-2. We find this selective advantage depends on expression of the cell surface protease, TMPRSS2 HGNC, that allows virus entry independent of endosomes thus avoiding antiviral IFITM proteins. SARS-CoV-2 virus lacking the S1/S2 furin CS was shed to lower titres from infected ferrets and was not transmitted to cohoused sentinel animals. Thus, the polybasic CS is a key determinant for efficient SARS-CoV-2 transmission.

    A Meta-analysis of Comorbidities in COVID-19 MESHD: Which Diseases increase the Susceptibility of SARS-CoV-2 Infection MESHD?

    Authors: Srinivasan Ramachandran; Manoj Kumar Singh; Ahmed Mobeen; Amit Chandra; Sweta Joshi

    id:10.20944/preprints202009.0486.v1 Date: 2020-09-21 Source: Preprints.org

    Background: Comorbidities have been frequently reported in COVID-19 MESHD patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection MESHD. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease MESHD(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 HGNC receptor and host proteases, namely FURIN HGNC and TMPRSS2 HGNC that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia MESHD (hereafter, referred as leukemia MESHD). The expression of ACE2 HGNC was also increased in psoriasis MESHD, lung cancer MESHD, Non-alcoholic fatty liver disease MESHD ( NAFLD MESHD), breast cancer MESHD, and pulmonary arterial hypertension MESHD patients. The expression of FURIN HGNC was higher in psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, and in type II diabetic liver MESHD, whereas it was lowered in breast cancer MESHD. Similarly, the expression of TMPRSS2 HGNC was increased during lung cancer MESHD and type II diabetes MESHD; it was decreased during psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, breast cancer MESHD, and cervical cancer MESHD.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia MESHD patients, as shown by the higher expression of IFNA2 HGNC, IFNA8 HGNC, IFNA10 HGNC, IFNA14 HGNC, IFNA16 HGNC, IFNA21 HGNC, IFNB1 HGNC, CXCL10 HGNC, and IL6 HGNC. The expression of JAK1 HGNC, STAT1 HGNC, IL6 HGNC, and CXCL10 HGNC was higher in NAFLD MESHD. Besides, JAK1 HGNC and STAT1 HGNC were upregulated in type II diabetic muscles MESHD. In addition, most of the upregulated genes in COVID-19 MESHD patients showed a similar trend in leukemia MESHD, NAFLD MESHD, and psoriasis MESHD. Furthermore, SARS-CoV-2, SARS-CoV MESHD and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection MESHD are mostly upregulated in leukemia MESHD patients; hence, leukemia MESHD patients are relatively more susceptible to develop COVID-19 MESHD, followed by other chronic disorders MESHD, such as, NAFLD MESHD, type II diabetes MESHD, psoriasis MESHD, and hypertension MESHD. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 MESHD and underlie COVID-19 MESHD associated comorbidities.

    Furin HGNC cleavage of SARS-CoV-2 Spike PROTEIN promotes but is not essential for infection and cell-cell fusion

    Authors: Guido Papa; Donna Mallery; Anna Albecka; Lawrence Welch; Jerome Cattin-Ortola; Jakub Luptak; David Paul; Harvey McMahon; Ian G. Goodfellow; Andrew P Carter; Sean P Munro; Leo C James

    doi:10.1101/2020.08.13.243303 Date: 2020-08-14 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects MESHD cells by binding to the host cell receptor Ace2 HGNC and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2 HGNC, which processes the viral Spike (S) protein PROTEIN to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin HGNC in order to prime S protein PROTEIN for TMPRSS2 HGNC processing. Here we show that CRISPR-Cas9 knockout of furin HGNC reduces, but does not prevent, the production of infectious SARS-CoV-2 MESHD virus. Comparing S processing in furin HGNC knockout cells to multibasic site mutants reveals that while loss of furin HGNC substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S MESHD S protein PROTEIN also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin HGNC in either donor or acceptor cells reduces, but does not prevent, TMPRSS2 HGNC-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin HGNC promotes both SARS-CoV-2 infectivity MESHD and cell-cell spread it is not essential, suggesting furin HGNC inhibitors will not prevent viral spread.

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HGNC Genes
SARS-CoV-2 Proteins


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