Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The open reading frame 3 of the severe acute respiratory syndrome coronavirus (SARS-CoV) genome encodes a predicted protein 3a, consisting of 274 amino acids, that lacks any significant similarities to any known protein. We generated specific antibodies against SARS protein 3a by using a synthetic peptide (P2) corresponding to amino acids 261-274 of the putative protein. Anti-P2 antibodies and the sera from SARS patients could specifically detect the recombinant SARS protein 3a expressed in Escherichia coli and in Vero E6 cells. Expression of SARS protein 3a was detected at 8-12 h after infection and reached a higher level after approximately 24 h in SARS-CoV-infected Vero E6 cells. Protein 3a was also detected in the alveolar lining pneumocytes and some intra-alveolar cells of a SARS-CoV-infected patient's lung specimen. Recombinant protein 3a expressed in Vero E6 cells and protein 3a in the SARS-CoV-infected cells was distributed over the cytoplasm in a fine punctate pattern with partly concentrated staining in the Golgi apparatus. Our study demonstrates that SARS-CoV indeed expresses a novel protein 3a, which is present only in SARS-CoV and not in other known CoVs.
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PMID:Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus. 1513 62

Two natural products databases, the marine natural products database (MNPD) and the traditional Chinese medicines database (TCMD), were used to find novel structures of potent SARS-CoV protease inhibitors through virtual screening. Before the procedure, the databases were filtered by Lipinski's ROF and Xu's extension rules. The results were analyzed by statistic methods to eliminate the bias in target-based database screening toward higher molecular weight compounds for enhancing the hit rate. Eighteen lead compounds were recommended by the screening procedure. They were useful for experimental scientists in prioritizing drug candidates and studying the interaction mechanism. The binding mechanism was also analyzed between the best screening compound and the SARS protein.
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PMID:SARS-CoV protease inhibitors design using virtual screening method from natural products libraries. 1569 56

We have tested the hypothesis that severe acute respiratory syndrome (SARS) coronavirus protein E (SCoVE) and its homologs in other coronaviruses associate through their putative transmembrane domain to form homooligomeric alpha-helical bundles in vivo. For this purpose, we have analyzed the results of molecular dynamics simulations where all possible conformational and aggregational space was systematically explored. Two main assumptions were considered; the first is that protein E contains one transmembrane alpha-helical domain, with its N- and C-termini located in opposite faces of the lipid bilayer. The second is that protein E forms the same type of transmembrane oligomer and with identical backbone structure in different coronaviruses. The models arising from the molecular dynamics simulations were tested for evolutionary conservation using 13 coronavirus protein E homologous sequences. It is extremely unlikely that if any of our assumptions were not correct we would find a persistent structure for all the sequences tested. We show that a low energy dimeric, trimeric and two pentameric models appear to be conserved through evolution, and are therefore likely to be present in vivo. In support of this, we have observed only dimeric, trimeric, and pentameric aggregates for the synthetic transmembrane domain of SARS protein E in SDS. The models obtained point to residues essential for protein E oligomerization in the life cycle of the SARS virus, specifically N15. In addition, these results strongly support a general model where transmembrane domains transiently adopt many aggregation states necessary for function.
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PMID:The transmembrane oligomers of coronavirus protein E. 1571 1

An immune antibody phage-display library was constructed from B cells of SARS convalescent patients. More than 80 clones were selected from the library by using the whole inactivated SARS-CoV virions as target. One human scFv, B1, was characterized extensively. The B1 recognized SARS pseudovirus in vivo and competed with SARS sera for binding to SARS-CoV with high affinity (equilibrium dissociation constant, K(d) = 105 nM). The B1 also has potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein in vitro. Finally, we found that the B1 recognized an epitope on S2 protein, especially within amino acids 1023-1189 of S2 protein. This study not only first made a human neutralizing antibody, which recognized an epitope on S2 protein like natural antibody in sera, but also may help us to better understand the immunological characteristics of SARS protein and SARS vaccine design.
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PMID:A human SARS-CoV neutralizing antibody against epitope on S2 protein. 1593 99

An antibody phage-display library was constructed from the B cells of convalescent severe acute respiratory syndrome (SARS) patients and screened using inactivated SARS coronavirus (CoV) virions as antigens. More than 80 positive clones were isolated from the library and one of them, scFv H12, was extensively characterized. scFv H12 bound to SARS-CoV with high affinity (equilibrium dissociation constant, Kd=73.5 nM), and neutralized SARS virions in vitro. The facts that scFv H12 bound to the SARS-S1 protein under non-reducing conditions and that it did not bind to monomeric S1 protein under reducing conditions strongly suggest that scFv H12 recognizes a conformational epitope shared by oligomeric S1 proteins. This study should aid in the manufacture of neutralizing antibody, provide a better understanding the immunological characteristics of SARS protein and facilitate the design of a SARS vaccine.
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PMID:A human neutralizing antibody against a conformational epitope shared by oligomeric SARS S1 protein. 1651 67

SARS-CoV-2 has devastated the world with its rapid spread and fatality. The researchers across the globe are struggling hard to search a drug to treat this infection. Understanding the time constraint, the best approach is to study clinically approved drugs for control of this deadly pandemic of COVID 19. The repurposing of such drugs can be supported with the study of molecular interactions to enhance the possibility of application. The present work is a molecular docking study of proteins responsible for viral propagation namely 3Clpro, Nsp10/16, Spike protein, SARS protein receptor binding domain, Nsp 9 viral single strand binding protein and viral helicase. The protein through virus enters the host cell-human angiotensin-converting enzyme 2 (ACE2) receptor, is also used as a target for molecular docking. The docking was done with most discussed drugs for SARS-CoV-2 like Ritonavir, Lopinavir, Remdesivir, Chloroquine, Hydroxychloroquine (HCQ), routine antiviral drugs like Oseltamivir and Ribavirin. In addition, small molecules with anti-inflammatory actions like Mycophenolic acid (MPA), Pemirolast, Isoniazid and Eriodictyol were also tested. The generated data confirms the potential of Ritonavir, Lopinavir and Remdesivir as a therapeutic candidate against SARS-CoV-2. It is observed that Eriodictyol binds to almost all selected target proteins with good binding energy, suggesting its importance in treatment of COVID 19. Molecular interactions of Ritonavir, Lopinavir and Remdesivir against SARS-CoV-2 proteins enhanced their potential as a candidate drug for treatment of COVID-19. Eriodictyol had emerged as a new repurposing drug that can be used in COVID-19.
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PMID:In silico molecular docking analysis for repurposing therapeutics against multiple proteins from SARS-CoV-2. 3275 69