Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronaviruses are positive-strand RNA viruses that translate their genome RNA into polyproteins that are co- and posttranslationally processed into intermediate and mature replicase nonstructural proteins (nsps). In murine hepatitis virus (MHV), nsps 1, 2, and 3 are processed by two papain-like proteinase activities within nsp3 (PLP1 and PLP2) to yield nsp1, an nsp2-3 intermediate, and mature nsp2 and nsp3. To determine the role in replication of processing between nsp2 and nsp3 at cleavage site 2 (CS2) and PLP1 proteinase activity, mutations were engineered into the MHV genome at CS2, at CS1 and CS2, and at the PLP1 catalytic site, alone and in combination. Mutant viruses with abolished cleavage at CS2 were delayed in growth and RNA synthesis but grew to wild-type titers of >10(7) PFU/ml. Mutant viruses with deletion of both CS1 and CS2 exhibited both a delay in growth and a decrease in peak viral titer to approximately 10(4) PFU/ml. Inactivation of PLP1 catalytic residues resulted in a mutant virus that did not process at either CS1 or CS2 and was severely debilitated in growth, achieving only 10(2) PFU/ml. However, when both CS1 and CS2 were deleted in the presence of inactivated PLP1, the growth of the resulting mutant virus was partially compensated, comparable to that of the CS1 and CS2 deletion mutant. These results demonstrate that interactions of PLP1 with CS1 and CS2 are critical for protein processing and suggest that the interactions play specific roles in regulation of the functions of nsp1, 2, and 3 in viral RNA synthesis.
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PMID:Replication of murine hepatitis virus is regulated by papain-like proteinase 1 processing of nonstructural proteins 1, 2, and 3. 1697 28

In less than eleven months, the world was brought to a halt by the COVID-19 outbreak. With hospitals becoming overwhelmed, one of the highest priorities concerned critical care triage to ration the scarce resources of intensive care units. Which patient should be treated first? Based on what clinical and biological criteria? A global joint effort rapidly led to sequencing the genomes of tens of thousands of COVID-19 patients to determine the patients' genetic signature that causes them to be at risk of suddenly developing severe disease. In this commentary, we would like to consider some points concerning the use of a multifactorial risk score for COVID-19 severity. This score includes macroautophagy (hereafter referred to as autophagy), a critical host process that controls all steps harnessed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Abbreviation list: ATG5: autophagy related 5; BECN1: beclin 1; COVID-19: coronavirus infectious disease-2019; EGR1: early growth response 1; ER: endoplasmic reticulum; DMVs: double-membrane vesicles; IBV: infectious bronchitis virus; MAP1LC3: microtubule associated protein 1 light chain 3; LC3-I: proteolytically processed, non-lipidated MAP1LC3; LC3-II: lipidated MAP1LC3; MEFs: mouse embryonic fibroblasts; MERS-CoV: Middle East respiratory syndrome-coronavirus; MHV: mouse hepatitis virus; NSP: non-structural protein; PEDV: porcine epidemic diarrhea virus; PLP2-TM: membrane-associated papain-like protease 2; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TGEV: transmissible gastroenteritis virus.
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PMID:A multifactorial score including autophagy for prognosis and care of COVID-19 patients. 3324 89