Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Feline calicivirus (FCV) is a major pathogen of cats associated with either respiratory disease or systemic disease, but its possible role as an enteric pathogen is neglected. Using RT-PCR, the RNA of FCV was identified in 25.9% (62/239) of stools of cats with enteritis and in 0/58 (0%) of cats without diarrhoea or other clinical signs. Isolates of enteric origin were obtained and a large 3.2-kb portion of the genome was sequenced, encompassing the 3' end of the RNA polymerase, the capsid protein precursor and the minor capsid protein. Also, the complete genome sequence of one such strain, the 160/2015/ITA, was determined. Upon sequence analysis, the enteric viruses were found to be genetically heterogeneous and to differ from each other and from isolates of respiratory origin. The enteric isolates were found to be more resistant to low pH conditions, to trypsin and to bile treatment than respiratory isolates. Overall, these findings are consistent with the hypothesis that some FCVs may acquire enteric tropism and eventually act as enteric pathogens. Whether this enteric tropism is maintained stably and whether it may affect, to some extent, the ability of the virus to trigger the classical and/or hypervirulent forms of disease should be assessed. Also, FCV should be included in the diagnostic algorithms of enteric diseases of cats to gain further information about FCV strains displaying enteric pathotype.
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PMID:Identification of feline calicivirus in cats with enteritis. 3235 95

Influenza A virus and coronavirus strains cause a mild to severe respiratory disease that can result in death. Although vaccines exist against circulating influenza A viruses, such vaccines are ineffective against emerging pandemic influenza A viruses. Currently, no vaccine exists against coronavirus infections, including pandemic SARS-CoV-2, the causative agent of the Coronavirus Disease 2019 (COVID-19). To combat these RNA virus infections, alternative antiviral strategies are needed. A key drug target is the viral RNA polymerase, which is responsible for viral RNA synthesis. In January 2020, the World Health Organisation identified enisamium as a candidate therapeutic against SARS-CoV-2. Enisamium is an isonicotinic acid derivative that is an inhibitor of multiple influenza B and A virus strains in cell culture and clinically approved in 11 countries. Here we show using in vitro assays that enisamium and its putative metabolite, VR17-04, inhibit the activity of the influenza virus and the SARS-CoV-2 RNA polymerase. VR17-04 displays similar efficacy against the SARS-CoV-2 RNA polymerase as the nucleotide analogue remdesivir triphosphate. These results suggest that enisamium is a broad-spectrum small molecule inhibitor of RNA virus RNA synthesis, and implicate it as a possible therapeutic option for treating SARS-CoV-2 infection. Unlike remdesivir, enisamium does not require intravenous administration which may be advantageous for the development of COVID-19 treatments outside a hospital setting.
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PMID:Enisamium is a small molecule inhibitor of the influenza A virus and SARS-CoV-2 RNA polymerases. 3251 88

Corona virus disease 2019 (COVID-19) is a respiratory disease caused by a new coronavirus (SARS-CoV-2) which causes significant morbidity and mortality. The emergence of this novel and highly pathogenic SARS-CoV-2 and its rapid international spread poses a serious global public health emergency. To date 32,174,627 cases, of which 962,613 (2.99%) have died, have been reported (https://www.who.int/westernpacific/health-topics/coronavirus, accessed 23 Sep 2020). The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. There are still not many SARS-CoV-2-specific and effective treatments or vaccines available. A second round of infection is obviously unavoidable. Aptamers had already been at the centre of interest in the fight against viruses before now. The selection and development of a new aptamer is, however, a time-consuming process. We therefore checked whether a clinically developed aptamer, BC 007, which is currently in phase 2 of clinical testing for a different indication, would also be able to efficiently bind DNA-susceptible peptide structures from SARS-CoV-2-spreading crucial proteins, such as the receptor binding domain (RBD) of the spike protein and the RNA dependent RNA polymerase of SARS-CoV-2 (re-purposing). Indeed, several such sequence-sections have been identified. In particular for two of these sequences, BC 007 showed specific binding in a therapy-relevant concentration range, as shown in Nuclear magnetic resonance (NMR)- and Circular dicroism (CD)-spectroscopy and isothermal titration calorimetry (ITC). The excellent clinical toxicity and tolerability profile of this substance opens up an opportunity for rapid clinical testing of its COVID-19 effectiveness.
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PMID:Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins. 3316 83


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