preVIEW: COVID-19

Corpus overview

Overview

MeSH Disease

Severe Acute Respiratory Syndrome (2241)

COVID-19 (1846)

Coronavirus Infections (362)

Pneumonia (174)

Death (125)


HGNC Genes

angiotensin I converting enzyme 2 (343)

interleukin 6 (61)

transmembrane serine protease 2 (55)

C-reactive protein (34)

CD4 molecule (24)


SARS-CoV-2 proteins

ProteinS (510)

ProteinN (122)

NSP5 (64)

ComplexRdRp (37)

ProteinE (32)


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    The impact of Spike mutations on SARS-CoV-2 neutralization

    Authors: Chloe Rees-Spear; Luke Muir; Sarah A Griffith; Judith Heaney; Yoann Aldon; Jonne Snitselaar; Peter Thomas; Carl Graham; Jeffrey Seow; Nayung Lee; Annachiara Rosa; Chloe Roustan; Catherine F Houlihan; Rogier W Sanders; Ravindra K Gupta; Peter Cherepanov; Hans Stauss; Eleni Nastouli; Katie J Doores; Marit J van Gils; Laura E McCoy; Max Crispin; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.15.426849 Date: 2021-01-19 Source: bioRxiv

    Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike PROTEIN. Antibodies from SARS-CoV-2 infection MESHD neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus MESHD or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5-10-fold. This work highlights that changes in the SARS-CoV-2 Spike PROTEIN can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

    Sterically-Confined Rearrangements of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein Control Cell Invasion

    Authors: Esteban Dodero Rojas; Jose Nelson Onuchic; Paul Whitford; Merissa Chen; Gokul N Ramadoss; Xiaoyan Guo; Alice Mac Kain; Quang Dinh Tran; Shion A Lim; Irene Lui; James Nunez; Sarah J Rockwood; Na Liu; Jared Carlson-Stevermer; Jennifer Oki; Travis Maures; Kevin Holden; Jonathan S Weissman; James A Wells; Bruce Conklin; Marco Vignuzzi; Martin Kampmann; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.18.427189 Date: 2021-01-19 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is highly contagious, and transmission involves a series of processes that may be targeted by vaccines and therapeutics. During transmission, host cell invasion is controlled by a large-scale conformational change of the Spike protein PROTEIN. This conformational rearrangement leads to membrane fusion, which creates transmembrane pores through which the viral genome is passed to the host. During Spike-protein PROTEIN-mediated fusion, the fusion peptides must be released from the core of the protein and associate with the host membrane. Interestingly, the Spike protein PROTEIN possesses many post-translational modifications, in the form of branched glycans that flank the surface of the assembly. Despite the large number of glycosylation sites, until now, the specific role of glycans during cell invasion has been unclear. Here, we propose that glycosylation is needed to provide sufficient time for the fusion peptides to reach the host membrane, otherwise the viral particle would fail to enter the host. To understand this process, an all-atom model with simplified energetics was used to perform thousands of simulations in which the protein transitions between the prefusion and postfusion conformations. These simulations indicate that the steric composition of the glycans induces a pause during the Spike protein PROTEIN conformational change. We additionally show that this glycan-induced delay provides a critical opportunity for the fusion peptides to capture the host cell. This previously-unrecognized role of glycans reveals how the glycosylation state can regulate infectivity of this pervasive pathogen.

    Tropism of SARS-CoV-2 MESHD for Developing Human Cortical Astrocytes

    Authors: Madeline G Andrews; Tanzila Mukhtar; Ugomma C Eze; Camille R Simoneau; Yonatan Perez; Mohammed A Mostajo-Radji; Shaohui Wang; Dmitry Velmeshev; Jahan Salma; G. Renuka Kumar; Alex A Pollen; Elizabeth E Crouch; Melanie Ott; Arnold R Kriegstein

    doi:10.1101/2021.01.17.427024 Date: 2021-01-18 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) readily infects MESHD a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms MESHD, which range in severity, accompany a significant proportion of COVID-19 MESHD cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 HGNC expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 HGNC and CD147 HGNC. Inhibition of DPP4 HGNC reduced infection and decreased expression of the cell stress marker, ARCN1 HGNC. We find tropism of SARS-CoV-2 MESHD for human astrocytes mediated by DPP4 HGNC, resulting in reactive gliosis-type injury MESHD.

    SARS-CoV-2 infection MESHD reduces Krüppel-Like Factor 2 HGNC in human lung autopsy MESHD

    Authors: Tzu-Han Lee; David Wu; Robert Guzy; Nathan Schoettler; Ayodeji Adegunsoye; Jeffrey Mueller; Aliya Hussein; Anne Sperling; Gokhan M Mutlu; Yun Fang

    doi:10.1101/2021.01.15.426691 Date: 2021-01-18 Source: bioRxiv

    Acute respiratory distress syndrome ( ARDS MESHD) occurred in ~12% of hospitalized COVID-19 MESHD patients in a recent New York City cohort. Pulmonary endothelial dysfunction MESHD, characterized by increased expression of inflammatory genes and increased monolayer permeability, is a major component of ARDS. Vascular leak results in parenchymal accumulation of leukocytes, protein, and extravascular water, leading to pulmonary edema MESHD, ischemia MESHD, and activation of coagulation associated with COVID-19 MESHD. Endothelial inflammation MESHD further contributes to uncontrolled cytokine storm in ARDS. We have recently demonstrated that Kruppel-like factor 2 HGNC ( KLF2 HGNC), a transcription factor which promotes endothelial quiescence and monolayer integrity, is significantly reduced in experimental models of ARDS. Lung inflammation MESHD and high-tidal volume ventilation result in reduced KLF2 HGNC, leading to pulmonary endothelial dysfunction MESHD and acute lung injury MESHD. Mechanistically, we found that KLF2 HGNC is a potent transcriptional activator of Rap guanine nucleotide exchange factor 3 HGNC ( RAPGEF3 HGNC) which orchestrates and maintains vascular integrity. Moreover, KLF2 HGNC regulates multiple genome-wide association study (GWAS)-implicated ARDS genes. Whether lung KLF2 HGNC is regulated by SARS-CoV-2 infection MESHD is unknown. Here we report that endothelial KLF2 HGNC is significantly reduced in human lung autopsies from COVID-19 MESHD patients, which supports that ARDS due to SARS-CoV-2 is a vascular phenotype possibly attributed to KLF2 HGNC down-regulation. We provide additional data demonstrating that KLF2 is down-regulated in SARS-CoV infection MESHD in mice.

    Large scale genomic and evolutionary study reveals SARS-CoV-2 virus isolates from Bangladesh strongly correlate with European origin and not with China.

    Authors: Mohammad Fazle Alam Rabbi; Md. Imran Khan; Saam Hasan; Mauricio Chalita; Kazi Nadim Hasan; Abu Sufian; Md. Bayejid Hosen; Mohammed Nafiz Imtiaz Polol; Jannatun Naima; Kihyun Lee; Yeong Ouk Kim; Mamudul Hasan Razu; Mala Khan; Md. Mizanur Rahman; Jongsik Chun; Md. Abdul Khaleque; Nur A Hasan; Rita R Colwell; Sharif Akhteruzzaman; Ilana Segal; Danielle Goldsmith; Shi Hong; Vinod Asundi; Erica M Briggs; Ngwe Sin Phyo; Markus Froehlich; Robert J Hogan; Ralph A Tripp; Sanjeev Anand; Thomas W. Campi; Michael Ford; Jonathan C. Reed; Bruce Onisko; Kent Matlack; Debendranath Dey; Jaisri R Lingappa; M Dharma Prasad; Anatoliy Kitaygorodskyy; Dennis Solas; Kumar Paulvannan; Vishwanath R Lingappa

    doi:10.1101/2021.01.17.425424 Date: 2021-01-18 Source: bioRxiv

    Rationale: The global public health is in serious crisis due to emergence of SARS-CoV-2 virus. Studies are ongoing to reveal the genomic variants of the virus circulating in various parts of the world. However, data generated from low- and middle-income countries are scarce due to resource limitation. This study was focused to perform whole genome sequencing of 151 SARS-CoV-2 isolates from COVID-19 MESHD positive Bangladeshi patients. The goal of this study was to identify the genomic variants among the SARS-CoV-2 virus isolates in Bangladesh, to determine the molecular epidemiology and to develop a relationship between host clinical trait with the virus genomic variants. Method: Suspected patients were tested for COVID-19 MESHD using one step commercial qPCR kit for SARS-CoV-2 Virus MESHD. Viral RNA was extracted from positive patients, converted to cDNA which was amplified using Ion AmpliSeq SARS-CoV-2 Research Panel. Massive parallel sequencing was carried out using Ion AmpliSeq Library Kit Plus. Assembly of raw data is done by aligning the reads to a pre-defined reference genome (NC_045512.2) while retaining the unique variations of the input raw data by creating a consensus genome. A random forest-based association analysis was carried out to correlate the viral genomic variants with the clinical traits present in the host. Result: Among the 151 viral isolates, we observed the 413 unique variants. Among these 8 variants occurred in more than 80 % of cases which include 241C to T, 1163A to T, 3037C to T,14408C to T, 23403A to G, 28881G to A, 28882 G to A, and finally the 28883G to C. Phylogenetic analysis revealed a predominance of variants belonging to GR clade, which have a strong geographical presence in Europe, indicating possible introduction of the SARS-CoV-2 virus into Bangladesh through a European channel. However, other possibilities like a route of entry from China cannot be ruled out as viral isolate belonging to L clade with a close relationship to Wuhan reference genome was also detected. We observed a total of 37 genomic variants to be strongly associated with clinical symptoms such as fever MESHD, sore throat, overall symptomatic status, etc. (Fishers Exact Test p-value<0.05). The most mention-worthy among those were the 3916CtoT (associated with causing sore throat, p-value 0.0005), the 14408C to T (associated with protection from developing cough, p-value= 0.027), and the 28881G to A, 28882G to A, and 28883G to C variant (associated with causing chest pain MESHD, p-value 0.025). Conclusion: To our knowledge, this study is the first large scale phylogenomic studies of SARS-CoV-2 virus circulating in Bangladesh. The observed epidemiological and genomic features may inform future research platform for disease management, vaccine development and epidemiological study.

    A Serology Strategy for Epidemiological Studies Based on the Comparison of the Performance of Seven Different Test Systems - The Representative COVID-19 MESHD Cohort Munich

    Authors: Laura Olbrich; Noemi Castelletti; Yannik Schaelte; Merce Gari; Peter Puetz; Abhishek Bakuli; Michael Pritsch; Inge Kroidl; Elmar Saathoff; Jessica Michelle Guggenbuehl Noller; Volker Fingerle; Ronan Le Gleut; Leonard Gilberg; Isabel Brand; Philine Falk; Alisa Markgraf; Flora Deak; Friedrich Riess; Max Diefenbach; Tabea M Eser; Franz Weinauer; Silke Martin; Ernst-Markus Quenzel; Marc Becker; Juergen Durner; Philipp Girl; Katharina Mueller; Katja Radon; Christiane Fuchs; Roman Woelfel; Jan Hasenauer; Michael Hoelscher; Andreas Wieser; Ranvijay Kumar Singh; Ashok Kumar Raman; Suresh Kumar Anandasadagopan; Parimala Karupannan; Subramanian Venkatesan; Harish Kumar Sardana; Anamika Kothari; Rishabh Jain; Anupma Thakur; Devendra Singh Parihar; Anas Saifi; Jasleen Kaur; Virendra Kumar; Avinash Mishra; Iranna Gogeri; Geetha Vani Rayasam; Praveen Singh; Rahul Chakraborty; Gaura Chaturvedi; Pinreddy Karunakar; Rohit Yadav; Sunanda Singhmar; Dayanidhi Singh; Sharmistha Sarkar; Purbasha Bhattacharya; Sundaram Acharya; Vandana Singh; Shweta Verma; Drishti Soni; Surabhi Seth; Firdaus Fatima; Shakshi Vashisht; Sarita Thakran; Akash Pratap Singh; Akanksha Sharma; Babita Sharma; Manikandan Subramanian; Yogendra Padwad; Vipin Hallan; Vikram Patial; Damanpreet Singh; Narendra Vijay Tirpude; Partha Chakrabarti; Sujay Krishna Maity; Dipyaman Ganguly; Jit Sarkar; Sistla Ramakrishna; Balthu Narender Kumar; Kiran A Kumar; Sumit G. Gandhi; Piyush Singh Jamwal; Rekha Chouhan; Vijay Lakshmi Jamwal; Nitika Kapoor; Debashish Ghosh; Ghanshyam Thakkar; Umakanta Subudhi; Pradip Sen; Saumya Raychaudhri; Amit Tuli; Pawan Gupta; Rashmi Kumar; Deepak Sharma; Rajesh P. Ringe; Amarnarayan D; Mahesh Kulkarni; Dhanasekaran Shanmugam; Mahesh Dharne; Syed G Dastager; Rakesh Joshi; Amita P. Patil; Sachin N Mahajan; Abu Junaid Khan; Vasudev Wagh; Rakeshkumar Yadav; Ajinkya Khilari; Mayuri Bhadange; Arvindkumar H. Chaurasiya; Shabda E Kulsange; Krishna khairnar; Shilpa Paranjape; Jatin Kalita; G.Narahari Sastry; Tridip Phukan; Prasenjit Manna; Wahengbam Romi; Pankaj Bharali; Dibyajyoti Ozah; Ravi Kumar Sahu; Elapaval VSSK Babu; Rajeev K Sukumaran; Aishwarya R Nair; Anoop Puthiyamadam; Prajeesh Kooloth Valappil; Adarsh Velayudhanpillai; Kalpana Chodankar; Samir Damare; Yennapu Madhavi; Ved Varun Agrawal; Sumit Dahiya; Anurag Agrawal; Debasis Dash; Shantanu Sengupta

    doi:10.1101/2021.01.13.21249735 Date: 2021-01-16 Source: medRxiv

    BackgroundSerosurveys are essential to understand SARS-CoV-2 exposure and enable population-level surveillance, but currently available tests need further in-depth evaluation. We aimed to identify testing-strategies by comparing seven seroassays in a population-based cohort. MethodsWe analysed 6,658 samples consisting of true-positives (n=193), true-negatives (n=1,091), and specimens of unknown status (n=5,374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2; and virus-neutralisation, GeneScript(R)cPass, VIRAMED-SARS-CoV-2-ViraChip MESHD(R), and Mikrogen-recomLine-SARS-CoV-2-IgG, including common-cold CoVs, for confirmatory testing. Statistical modelling generated optimised assay cut-off-thresholds. FindingsSensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3%; for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturers/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median titres remained stable for at least 90-120 days after RT-PCR-positivity. Of true-positives with positive RT-PCR (<30 days), 6.7% did not mount detectable seroresponses. Virus-neutralisation was 73.8% sensitive, 100.0% specific (1:10 dilution). Neutralisation surrogate tests (GeneScript(R)cPass, Mikrogen-recomLine-RBD) were >94.9% sensitive, >98.1% specific. Seasonality had limited effects; cross-reactivity with common-cold CoVs 229E and NL63 in SARS-CoV-2 true-positives was significant. ConclusionOptimised cut-offs improved test performances of several tests. Non-reactive serology in true-positives was uncommon. For epidemiological purposes, confirmatory testing with virus-neutralisation may be replaced with GeneScript(R)cPass or recomLine-RBD. Head-to-head comparisons given here aim to contribute to the refinement of testing-strategies for individual and public health use.

    N-(4-Hydroxyphenyl)retinamide suppresses SARS-CoV-2 spike PROTEIN protein-mediated cell-cell fusion and viral infection in vitro  MESHD

    Authors: Yasuhiro Hayashi; Kiyoto Tsuchiya; Mizuki Yamamoto; Yoko Nemoto-Sasaki; Kazunari Tanigawa; Kotaro Hama; Takashi Tanikawa; Jin Gohda; Kenji Maeda; Jun-ichiro Inoue; Atsushi Yamashita

    doi:10.21203/rs.3.rs-148750/v1 Date: 2021-01-16 Source: ResearchSquare

    The coronavirus disease ( COVID-19 MESHD) pandemic, caused by severe acute r espiratory syndrome coronavirus 2 MESHD(SARS-CoV-2), persists worldwide with limited therapeutic options. Since membrane fusion between SARS-CoV-2 and host cells is essential for the early step of the i nfection, MESHD the membrane compositions, including sphingolipids, in host cells are considered to affect the v iral infection. MESHD However, the role of sphingolipids in the life cycle of S ARS-CoV-2 MESHDremains unclear. Here, we assessed several inhibitors of sphingolipid metabolism enzymes against SARS-CoV-2 spike PROTEIN protein-mediated cell-cell fusion and v iral infection MESHDin vitro. Among the compounds tested, only N-(4-hydroxyphenyl)retinamide (4-H PR, HGNC also known as fenretinide), an inhibitor of dihydroceramide Δ4-desaturase 1 (D ES1) HGNC and well known for having antitumour activity, suppressed cell-cell fusion (50% effective concentration [EC50] = 4.1 mM) and v iral infection MESHD([EC50] = 4.4 mM), wherein the EC50 values are below its plasma concentration in previous clinical trials on t umours. MESHD D ES1 HGNCcatalyses the introduction of a double bond in dihydroceramide, and the inhibition efficiencies observed were consistent with an increased ratio of saturated sphinganine-based lipids to total sphingolipids and the decreased cellular membrane fluidity. These findings, together with the accumulated clinical data regarding the safety of 4-H PR, HGNC make it a likely candidate drug to treat COVID-19 MESHD.

    Bacterial superinfection pneumonia MESHD in SARS-CoV-2 respiratory failure MESHD

    Authors: Chiagozie O. Pickens; Catherine A. Gao; Michael J. Cuttica; Sean B. Smith; Lorenzo Pesce; Rogan Grant; Mengjia Kang; Luisa Morales-Nebreda; Avni A. Bavishi; Jason Arnold; Anna Pawlowski; Chao Qi; GR Scott Budinger; Benjamin D. Singer; Richard G. Wunderink; - NU COVID Investigators; Natalie J Thornburg; Panayampalli S Satheshkumar; Xiaowu Liang; Richard B Kennedy; Angela Yee; Michael Townsend; Joseph J Campo; Michael W Mather; Rik GH Lindeboom; Emma Dann; Ni Huang; Krzysztof Polanski; Elena Prigmore; Florian Gothe; Jonathan Scott; Rebecca P Payne; Kenneth F Baker; Aidan T Hanrath; Ina CD Schim van der Loeff; Andrew S Barr; Amada Sanchez-Gonzalez; Laura Bergamaschi; Federica Mescia; Josephine L Barnes; Eliz Kilich; Angus de Wilton; Anita Saigal; Aarash Saleh; Sam M Janes; Claire M Smith; Nusayhah Gopee; Caroline Wilson; Paul Coupland; Jonathan M Coxhead; Vladimir Y Kiselev; Stijn van Dongen; Jaume Bacardit; Hamish W King; Anthony J Rostron; A John Simpson; Sophie Hambleton; Elisa Laurenti; Paul A Lyons; Kerstin B Meyer; Marko Z Nikolic; Christopher JA Duncan; Ken Smith; Sarah A Teichmann; Menna R Clatworthy; John C Marioni; Berthold Gottgens; Muzlifah Haniffa

    doi:10.1101/2021.01.12.20248588 Date: 2021-01-15 Source: medRxiv

    BackgroundSevere community-acquired pneumonia MESHD secondary to SARS-CoV-2 is a leading cause of death MESHD. Current guidelines recommend patients with SARS-CoV-2 pneumonia MESHD receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations. MethodsWe obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia MESHD requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia MESHD ( VAP MESHD) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care. ResultsThe 179 ventilated patients with severe SARS-CoV-2 pneumonia MESHD discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days. ConclusionsWith use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia MESHD. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP MESHD in ventilated patients with SARS-CoV-2 pneumonia MESHD are higher than historically reported.

    CAR HGNC-NK Cells Effectively Target the D614 and G614 SARS-CoV-2-infected Cells MESHD

    Authors: Gourab Prasad Pattnaik; Surajit Bhattacharjya; Hirak Chakraborty; Yechun Xu; Chunfan Huang; Can Jin; Zhenyun Du; Xia Chen; Yaqi Ding; Hao Sun; Meixia Li; Rongjuan Pei; Shihai Zhang; Minbo Su; Yi Zhang; Jia Li; Laura Esparcia; Ana Marcos-Jimenez; Santiago Sanchez-Alonso; Irene Llorente; Joan B. Soriano; Carmen Suarez Fernandez; Rosario Garcia-Vicuna; Julio Ancochea; Jesus Sanz; Cecilia Munoz-Calleja; Rafael de la Camara; Alfonso Canabal Berlanga; Isidoro Gonzalez-Alvaro; Laura Cardenoso; John R Bradley

    doi:10.1101/2021.01.14.426742 Date: 2021-01-15 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly contagious presenting a significant public health issue. Current therapies used to treat coronavirus disease 2019 MESHD ( COVID-19 MESHD) include monoclonal antibody cocktail, convalescent plasma, antivirals, immunomodulators, and anticoagulants, though the current therapeutic options remain limited and expensive. The vaccines from Pfizer and Moderna have recently been authorized for emergency use, which are invaluable for the prevention of SARS-CoV-2 infection MESHD. However, their long-term side effects are not yet to be documented, and populations with immunocompromised conditions (e.g., organ-transplantation and immunodeficient MESHD patients) may not be able to mount an effective immune response. In addition, there are concerns that wide-scale immunity to SARS-CoV-2 may introduce immune pressure that could select for escape mutants to the existing vaccines and monoclonal antibody therapies. Emerging evidence has shown that chimeric antigen receptor ( CAR HGNC)- natural killer (NK) immunotherapy has potent antitumor response in hematologic cancers MESHD with minimal adverse effects in recent studies, however, the potentials of CAR HGNC-NK cells in preventing and treating severe cases of COVID-19 MESHD has not yet been fully exploited. Here, we improve upon a novel approach for the generation of CAR HGNC-NK cells for targeting SARS-CoV-2 and its D614G mutant. CAR HGNC-NK cells were generated using the scFv domain of S309 (henceforward, S309- CAR HGNC-NK), a SARS-CoV and SARS-CoV-2 MESHD neutralizing antibody that targets the highly conserved region of SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN ( S) glycoprotein PROTEIN, therefore would be more likely to recognize different variants of SARS-CoV-2 isolates. S309- CAR HGNC-NK cells can specifically bind to pseudotyped SARS-CoV-2 virus and its D614G mutant. Furthermore, S309- CAR HGNC-NK cells can specifically kill target cells expressing SARS-CoV-2 S protein PROTEIN in vitro and show superior killing activity and cytokine production, compared to that of the recently published CR3022- CAR HGNC-NK cells. Thus, these results pave the way for generating off-the-shelf S309- CAR HGNC-NK cells for treatment in high-risk individuals as well as provide an alternative strategy for patients unresponsive to current vaccines.

    Enhanced Cholesterol-dependent Hemifusion by Internal Fusion Peptide 1 of SARS Coronavirus-2 Compared to its N-terminal Counterpart

    Authors: Gourab Prasad Pattnaik; Surajit Bhattacharjya; Hirak Chakraborty; Yechun Xu; Chunfan Huang; Can Jin; Zhenyun Du; Xia Chen; Yaqi Ding; Hao Sun; Meixia Li; Rongjuan Pei; Shihai Zhang; Minbo Su; Yi Zhang; Jia Li; Laura Esparcia; Ana Marcos-Jimenez; Santiago Sanchez-Alonso; Irene Llorente; Joan B. Soriano; Carmen Suarez Fernandez; Rosario Garcia-Vicuna; Julio Ancochea; Jesus Sanz; Cecilia Munoz-Calleja; Rafael de la Camara; Alfonso Canabal Berlanga; Isidoro Gonzalez-Alvaro; Laura Cardenoso; John R Bradley

    doi:10.1101/2021.01.14.426613 Date: 2021-01-15 Source: bioRxiv

    Membrane fusion is an important step for the entry of the lipid-sheathed viruses into the host cells. The fusion process is being carried out by fusion proteins present in the viral envelope. The class I viruses contains a 20-25 amino acid sequence at its N-terminal of the fusion domain, which is instrumental in fusion, and is termed as fusion peptide. However, Severe Acute Respiratory Syndrome Coronavirus (SARS) coronaviruses MESHD contain more than one fusion peptide sequences. We have shown that the internal fusion peptide 1 ( IFP1 HGNC) of SARS-CoV MESHD is far more efficient than its N-terminal counterpart (FP) to induce hemifusion between small unilamellar vesicles. Moreover, the ability of IFP1 HGNC to induce hemifusion formation increases dramatically with growing cholesterol content in the membrane. Interestingly, IFP1 HGNC is capable of inducing hemifusion, but fails to open pore.

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HGNC Genes
SARS-CoV-2 Proteins

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