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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (33)

ComplexRdRp (33)

ProteinE (8)

ProteinS (8)

ORF3a (5)


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SARS-CoV-2 Proteins
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    Healthcare workers in elderly care: a source of silent SARS-CoV-2 transmission?

    Authors: Mirjam Jeanne Dorine Dautzenberg; Andrea Eikelenboom-Boskamp; Jacqueline Janssen; Miranda Drabbe; Ewoud de Jong; Eefke Weesendorp; Marion Koopmans; Andreas Voss

    doi:10.1101/2020.09.07.20178731 Date: 2020-09-09 Source: medRxiv

    Importance: Healthcare workers (HCWs), including those with mild symptoms, may be an important source of COVID-19 MESHD within elderly care. Objective: To gain insight into the spread of SARS-CoV-2 among HCWs working in elderly care settings. Design: Cross-sectional study among HCWs working in elderly care in the South-East of the Netherlands, testing for SARS-CoV-2, between March 31 and April 17, 2020. Setting: HCWs working in geriatric rehabilitation, somatic and psychogeriatric wards or small-scale living groups and district nursing, with a total of 5245 HCWs within 4 organisations. Participants: 621 HCWs with mild respiratory symptoms. Main Outcomes: Number of HCWs testing positive for SARS-CoV-2 in pharyngeal swabs, using real-time reverse-transcriptase PCR targeting the SARS-CoV-2 E-gene PROTEIN, N-gene PROTEIN, and RdRP PROTEIN. HCWs filled out a survey to collect information on symptoms and possible sources of infection. Results: 133/615 (21.6%) HCWs tested positive for SARS-CoV-2, ranging from 15.6 to 44.4% per elderly care organisation, and from 0 to 64.3% per separate location of the organizations, respectively. 74.6% of tested HCWs were nursing staff, 1.7% elderly care physicians, 20.3% other HCWs with patient contact and 3.4% HCWs without patient contact. In the univariate analysis, fever MESHD, runny or stuffy nose, anosmia MESHD, general malaise, myalgia MESHD, headache MESHD and ocular pain MESHD were associated with SARS-CoV-2 positivity, while gastro-intestinal symptoms and respiratory symptoms, other than runny or stuffy nose were not. Risk factors for SARS-CoV-2 positivity were contact with patients or colleagues with suspected or proven COVID-19 MESHD. Whole genome sequencing of 22 samples in 2 facilities strongly suggests spread within facilities. Conclusions and Relevance: We found a high SARS-CoV-2 prevalence among HCWs in nursing homes and district nursing, supporting the hypothesis of undetected spread within elderly care facilities. Structural testing of elderly care HCWs, including track and trace of contacts, should be performed to control this spread, even when only mild symptoms are present.

    Temporal landscape of mutation accumulation in SARS-CoV-2 genomes from Bangladesh: possible implications from the ongoing outbreak in Bangladesh

    Authors: Otun Saha; Rokaiya Nurani Shatadru; Nadira Naznin Rakhi; Israt Islam; Md. Shahadat Hossain; Md. Mizanur Rahaman; Leo C James; Madeline A Lancaster; Zhu Shu; Zhiming Yuan; Lei Tong; Han Xia; Jingzhe Pan; Natalie Garton; Manish Pareek; Michael Barer; Craig J Smith; Stuart M Allan; Michelle M. Lister; Hannah C. Howson-Wells; Edward C Holmes; Matthew W. Loose; Jonathan K. Ball; C. Patrick McClure; - The COVID-19 Genomics UK consortium study group; Shi Chen

    doi:10.1101/2020.08.20.259721 Date: 2020-08-21 Source: bioRxiv

    Along with intrinsic evolution, adaptation to selective pressure in new environments might have resulted in the circulatory SARS-CoV-2 strains in response to the geoenvironmental conditions of a country and the demographic profile of its population. Thus the analysis of genomic mutations of these circulatory strains may give an insight into the molecular basis of SARS-CoV-2 pathogenesis and evolution favoring the development of effective treatment and containment strategies. With this target, the current study traced the evolutionary route and mutational frequency of 198 Bangladesh originated SARS-CoV-2 genomic sequences available in the GISAID platform over a period of 13 weeks as of 14 July 2020. The analyses were performed using MEGA 7, Swiss Model Repository, Virus Pathogen Resource and Jalview visualization. Our analysis identified that majority of the circulating strains in the country belong to B and/or L type among cluster A to Z and strikingly differ from both the reference genome and the first sequenced genome from Bangladesh. Mutations in Nonspecific protein 2 ( NSP2 PROTEIN NSP2 HGNC), NSP3 PROTEIN NSP3 HGNC, RNA dependent RNA polymerase PROTEIN ( RdRp PROTEIN), Helicase HGNC, Spike, ORF3a PROTEIN, and Nucleocapsid (N) protein PROTEIN were common in the circulating strains with varying degrees and the most unique mutations(UM) were found in NSP3 HGNC NSP3 PROTEIN (UM-18). But no or limited changes were observed in NSP9 PROTEIN, NSP11 PROTEIN, E (Envelope), NSP7a, ORF 6, and ORF 7b suggesting the possible conserved functions of those proteins in SARS-CoV-2 propagation. However, along with D614G mutation, more than 20 different mutations in the Spike protein PROTEIN were detected basically in the S2 domain. Besides, mutations in SR-rich region of N protein PROTEIN and P323L in RDRP PROTEIN were also present. However, the mutation accumulation showed an association with sex and age of the COVID-19 MESHD positive cases. So, identification of these mutational accumulation patterns may greatly facilitate drug/ vaccine development deciphering the age and the sex dependent differential susceptibility to COVID-19 MESHD.

    Retesting Positive for SARS-CoV-2 RNA in Recovered COVID-19 MESHD Patients Reveals Low Levels of Non-Replicating Virus

    Authors: Flora Marzia Liotti; Giulia Menchinelli; Simona Marchetti; Rosalba Ricci; Brunella Posteraro; Francesco Landi; Maurizio Sanguinetti; Paola Cattani

    doi:10.21203/rs.3.rs-59323/v1 Date: 2020-08-14 Source: ResearchSquare

    Background: The follow-up of COVID-19 MESHD recovered patients is especially important to assess their infectivity and/or transmissibility statuses in order to maximize the COVID-19 MESHD management and containment. The aim of this study was to determine both total (genomic) and replicative (sub-genomic) SARS-CoV-2 RNA levels in nasal/oropharyngeal swab (NOS) samples from patients at follow-up times after COVID-19 MESHD recovering. Materials/methods: We tested 176 NOS samples of COVID-19 MESHD recovered patients who were followed up at the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from 21 April to 18 June 2020, according to our COVID-19 MESHD care protocol. The RT-PCR tests were performed using the Allplex™ 2019-nCoV and the Quanty COVID-19 MESHD assays (for total RNA detection and quantification, respectively) and an in-house assay (for replicative RNA detection).  Results: Of 176 NOS samples studied, 32 (18.2%) tested positive for total RNA, with CT values ranging from 29.3 to 38.8 for E, RdRP PROTEIN, and N genes PROTEIN (9 samples), 32.2 to 39.3 for RdRP PROTEIN and N genes PROTEIN (7 samples) or 35.8 to 39.8 for the N gene PROTEIN (16 samples). Consistently, viral loads ranged from 1.6 × 101 to 1.3 × 104 RNA copies/mL. Interestingly, we found replicative RNA in only one of 32 positive samples based on the presence of E-gene PROTEIN sub-genomic RNA (CT value of 39.1). The CT value (29.3) of E-gene PROTEIN genomic RNA in this sample was the lowest among the CT values of all 9 samples in which the E gene PROTEIN was detected. Testing samples obtained from the 32 patients at the time of COVID-19 MESHD diagnosis showed that the CT values ranged from 17.1 to 38.1 for E, RdRP PROTEIN, and N genes PROTEIN. Of note, the mean CT value of E-gene PROTEIN sub-genomic RNA (34.9) in these samples differed of 9.0 ± 2.8 from the mean CT value of E-gene PROTEIN genomic RNA (25.9). Finally, all but one of the 32 patients had positive serology results against SARS-CoV-2. Conclusions: Our findings show that at least a proportion of COVID-19 MESHD recovered patients were still positive for SARS-CoV-2 RNA, despite to a lower extent, and that only a minority of them was likely to have actively replicating virus in the upper respiratory tract.

    Discovery of Natural Phenol Catechin as a Multitargeted Agent Against SARS-CoV-2 For the Plausible Therapy of COVID-19 MESHD

    Authors: Chandra Bhushan Mishra; Preeti Pandey; Ravi Datta Sharma; Raj Kumar Mongre; Andrew M Lynn; Rajendra Prasad; Raok Jeon; Amresh Prakash

    doi:10.26434/chemrxiv.12752402.v1 Date: 2020-08-04 Source: ChemRxiv

    The global pandemic crisis, COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus MESHD 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19 MESHD. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S PROTEIN) glycoprotein, human angiotensin-converting enzyme 2 ( hACE2 HGNC), 3-chymotrypsin- like cysteine protease PROTEIN ( 3CLpro PROTEIN), Cathepsin L HGNC, Nucleocapsid protein PROTEIN, RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) and nonstructural protein 6 ( NSP6 PROTEIN) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro PROTEIN, Cathepsin L HGNC, RBD of S protein PROTEIN, NSP-6, and Nucleocapsid protein PROTEIN. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol ( Cathepsin L HGNC) to -26.09 kcal/mol ( NSP6 PROTEIN). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19 MESHD.

    Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

    Authors: L Ponoop Prasad Patro; Chakkarai Sathyaseelan; Patil Pranita Uttamrao; Thenmalarchelvi Rathinavelan

    doi:10.1101/2020.07.31.230987 Date: 2020-07-31 Source: bioRxiv

    To accelerate the drug and vaccine development against the severe acute respiratory syndrome MESHD virus 2 (SARS-CoV-2), a comparative analysis of SARS-CoV-2 proteome has been performed in two phases by considering manually curated 31389 whole genome sequences from 84 countries. Among the 9 mutations that occur at a high significance (T85I-NPS2, L37F- NSP6 PROTEIN, P323L- NSP12 PROTEIN, D614G-spike, Q57H- ORF3a PROTEIN, G251V- ORF3a PROTEIN, L84S- ORF8 PROTEIN, R203K-nucleocapsid and G204R-nucleocapsid), R203K-nucleocapsid and G204R-nucleocapsid are co-occurring (dependent) mutations and P323L- NSP12 PROTEIN and D614G-spike often appear simultaneously. Other notable variations that appear with a moderate to low significance are, M85- NSP1 HGNC deletion, D268- NSP2 HGNC NSP2 PROTEIN deletion, 112 amino acids deletion in ORF8 PROTEIN, a phenylalanine insertion amidst F34-F36 ( NSP6 PROTEIN) and several co-existing (dependent) substitution/deletion (I559V & P585S in NSP2 HGNC NSP2 PROTEIN, P504L & Y541C in NSP13 PROTEIN, G82 & H83 deletions in NSP1 HGNC and K141, S142 & F143 deletions in NSP2 HGNC NSP2 PROTEIN) mutations. P323L- NSP12 PROTEIN, D614G-spike, L37F- NSP6 PROTEIN, L84S- ORF8 PROTEIN and the sequences deficient of the high significant mutations have led to 4 major SARS-CoV-2 clades. The top 5 countries bearing all the high significant and majority of the moderate significant mutations are: USA, England, Wales, Australia and Scotland. Further, the majority of the significant mutations have evolved in the first phase and have already transmitted around the globe indicating the positive selection pressure. Among the 26 SARS-CoV-2 proteins, nucleocapsid PROTEIN protein, ORF3a PROTEIN, ORF8 PROTEIN, RNA dependent RNA polymerase PROTEIN and spike exhibit a higher heterogeneity compared with the rest of the proteins. However, NSP9 PROTEIN, NSP10 PROTEIN, NSP8 PROTEIN, the envelope protein PROTEIN and NSP4 HGNC NSP4 PROTEIN are highly resistant to mutations and can be exploited for drug/vaccine development.

    Dynamic tracking of variant frequencies depicts the evolution of mutation sites amongst SARS-CoV-2 genomes from India

    Authors: Gaurav Sharma; Vaishnavi Kolte; Shenu Hudson B.; Azra Khan

    doi:10.1101/2020.07.14.201905 Date: 2020-07-14 Source: bioRxiv

    With the exponential spread of COVID-19 MESHD COVID-19 MESHD pandemic across the world within the last six months, SARS-CoV-2 strains are continuously trying to adapt themselves in their host environment by random mutations. While doing so, some variants with evolutionary advantages such as better human to human transmissibility potential should get naturally selected. This short communication demonstrates how the mutation probability patterns are evolving in 864 SAR-CoV-2 strains isolated from COVID-19 MESHD patients across diverse Indian states. We have identified 30 such variants showing contrasting mutational probabilities in the span of four months. Out of these, the mutational probabilities of 25 variants including C14408T (in RdRp PROTEIN gene), A23403G (in spike gene), C6312A ( nsp3 HGNC gene) are continuously increasing suggesting that these mutations are being propagated with time due to their unexplored evolutionary advantages. In contrast, the mutational probabilities of five variants including C6312A ( nsp3 HGNC gene), G11083T (nsp6 gene), C28311T ( N gene PROTEIN) have significantly decreased in May-June as compared to March-April, suggesting these mutations are being terminated with time. Further in-depth investigation of these identified variants will provide valuable knowledge about the evolution, infection strategies, transmission rates, and epidemiology of SARS-CoV-2 in India.

    A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 MESHD Patients

    Authors: Dharmendra Kumar Maurya

    doi:10.26434/chemrxiv.12630539.v1 Date: 2020-07-09 Source: ChemRxiv

    The current outbreak of the corona virus disease 2019 ( COVID-19 MESHD), has affected almost entire world and become pandemic now. Currently, there is neither any FDA approved drugs nor any vaccines available to control it. Very recently in Bangladesh, a group of doctors reported astounding success in treating patients suffering from COVID-19 MESHD with two commonly used drugs, Ivermectin and Doxycycline. In the current study we have explored the possible mechanism by which these drugs might have worked for the positive response in the COVID-19 MESHD patients. To explore the mechanism we have used molecular docking and molecular dynamics simulation approach. Effectiveness of Ivermectin and doxycycline were evaluated against Main Protease PROTEIN ( Mpro PROTEIN), Spike (S) protein PROTEIN, Nucleocapsid (N PROTEIN), RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN, NSP12 PROTEIN), ADP Ribose Phosphatase ( NSP3 HGNC NSP3 PROTEIN), Endoribonuclease ( NSP15 PROTEIN) and methyltransferase ( NSP10 PROTEIN- NSP16 PROTEIN complex) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) receptor. Our study shows that both Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins but Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding site to the Spike-RBD and ACE2 HGNC interacting region indicating that it might be interfering in the interaction of spike with ACE2 HGNC and preventing the viral entry in to the host cells. Ivermectin also exhibited significant binding affinity with different SARS-CoV-2 structural and non-structural proteins (NSPs) which have diverse functions in virus life cycle. Significant binding of Ivermectin with RdRp PROTEIN indicate its role in the inhibition of the viral replication and ultimately impeding the multiplication of the virus. Ivermectin also possess significant binding affinity with NSP3 HGNC NSP3 PROTEIN, NSP10 PROTEIN, NSP15 PROTEIN and NSP16 PROTEIN which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro PROTEIN, Spike, NSP3 HGNC NSP3 PROTEIN, NSP16 PROTEIN and ACE2 HGNC was quiet stable. Thus, our docking and simulation studies reveal that combination of Ivermectin and doxycycline might be executing the effect by inhibition of viral entry and enhance viral load clearance by targeting various viral functional proteins.

    Evaluation of Different PCR Assay Formats for Sensitive and Specific Detection of SARS-CoV-2 RNA

    Authors: Jeremy Ratcliff; Dung Nguyen; Monique Andersson; Peter Simmonds

    doi:10.1101/2020.06.24.168013 Date: 2020-06-24 Source: bioRxiv

    Accurate identification of individuals infected with SARS-CoV-2 is crucial for efforts to control the ongoing COVID-19 MESHD COVID-19 MESHD pandemic. Polymerase chain reaction (PCR)-based assays are the gold standard for detecting viral RNA in patient samples and are used extensively in clinical settings. Most currently used quantitative PCR (RT-qPCRs) rely upon real-time detection of PCR product using specialized laboratory equipment. To enable the application of PCR in resource-poor or non-specialist laboratories, we have developed and evaluated a nested PCR method for SARS-CoV-2 RNA using simple agarose gel electrophoresis for product detection. Using clinical samples tested by conventional qPCR methods and RNA transcripts of defined RNA copy number, the nested PCR based on the RdRP PROTEIN gene demonstrated high sensitivity and specificity for SARS-CoV-2 RNA detection in clinical samples, but showed variable and transcript length-dependent sensitivity for RNA transcripts. Samples and transcripts were further evaluated in an additional N protein PROTEIN real-time quantitative PCR assay. As determined by 50% endpoint detection, the sensitivities of three RT-qPCRs and nested PCR methods varied substantially depending on the transcript target with no method approaching single copy detection. Overall, these findings highlight the need for assay validation and optimization and demonstrate the inability to precisely compare viral quantification from different PCR methodologies without calibration.

    Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the "confined virus"?

    Authors: Tarek Alouane; Meriem Laamarti; Abdelomunim Essabbar; Mohammed Hakmi; El Mehdi Bouricha; M.W. Chemao-Elfihri; Souad Kartti; Nasma Boumajdi; Houda Bendani; Rokia Laamarti; Fatima Ghrifi; Loubna Allam; Tarik Aanniz; Mouna Ouadghiri; Naima El Hafidi; Rachid El Jaoudi; Houda Benrahma; Jalil El Attar; Rachid Mentag; Laila Sbabou; Chakib Nejjari; Saaid Amzazi; Lahcen Belyamani; Azeddine Ibrahimi

    doi:10.1101/2020.06.20.163188 Date: 2020-06-21 Source: bioRxiv

    The COVID-19 MESHD COVID-19 MESHD pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from December 24, 2019, to May 13, 2020, according to the GISAID database. Our analysis revealed the presence of 3,206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (> 10%) have been identified at different locations along the viral genome; eight in ORF1ab PROTEIN polyprotein (in nsp2 HGNC, nsp3 HGNC, transmembrane domain, RdRp PROTEIN, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein PROTEIN and one in each of three proteins: spike PROTEIN, ORF3a PROTEIN, and ORF8 PROTEIN. Moreover, 36 non-synonymous mutations were identified in the RBD of the spike protein PROTEIN with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike PROTEIN protein to the human ACE2 HGNC receptor. These results along with mutational frequency dissimilarity and intra-genomic divergence of SARS-CoV-2 could indicate that the SARS-CoV-2 is not yet adapted to its host. Unlike the influenza virus or HIV viruses, the low mutation rate of SARS-CoV-2 makes the development of an effective global vaccine very likely.

    Epidemiological description and analysis of RdRp PROTEIN, E and N genes PROTEIN dynamic by RT-PCR of SARS-CoV-2 in Moroccan population: Experience of the National Reference Laboratory (LNR)-UM6SS

    Authors: Houda Benrahma; Idrissa Diawara; Imane Smyej; Jalila Rahoui; Nida Meskaouni; Rachid Benmessaoud; Khadija Arouro; Khadija Jaras; Zahra Adam; Salma Nahir; Zineb Aouzal; Hajar Elguazzar; Leila Jeddane; Fadwa Ousti; Jalila Elbakkouri; Chakib Nejjari

    doi:10.1101/2020.06.18.20135137 Date: 2020-06-20 Source: medRxiv

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease MESHD that first emerged in Hubei province, China, in December 2019. On 2 March 2020, the Moroccan Ministry of Health confirmed the first COVID-19 MESHD case in Morocco. The new virus SARS-CoV-2 was identified in the sample of a Moroccan expatriate residing in Italy. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. This study aims to analyze the epidemiological profile of the SARS-CoV-2 in Moroccan cases and to investigate the dynamic of RdRp PROTEIN gene, N PROTEIN gene, and E PROTEIN gene in patients from diagnosis until the recovery. Among 859 Covid-19 MESHD RT-PCR tests realized for 285 patients, 133 cases had positive results Covid-19 MESHD. 9 % of these cases present the 3 genes RdRp PROTEIN, N, and E, 47% only the RdRp PROTEIN gene, 2% with RdRp PROTEIN and N gene PROTEIN, 26% cases are positives with N gene PROTEIN, and 16 % with N and E gene PROTEIN. The analysis of the Covid-19 MESHD genes ( RdRp PROTEIN, N, and E) dynamic reveal that more than 6% stay positive with detection of the N and E gene PROTEIN, and 14% with the N gene PROTEIN after 12 days of treatment. The median period from positive to the first negative Covid-19 MESHD RT-PCR tests was 6.8{+/-}2.24 days for 44% cases, 14.31 {+/-} 2.4 days for 30%, and 22.67 {+/-} 1.21 days for 4%. This a first description of the Moroccan COVID-19 MESHD cases and the analysis of the dynamic of the 3 genes RdRp PROTEIN, N, and E. The analysis of our population can help to involved in the care of patients.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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