Disease relevance of HRVBgp1

• Structure of human rhinovirus 3C protease reveals a trypsin-like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein [1].
• Implications of the picornavirus capsid structure for polyprotein processing [2].
• Human rhinovirus, the chief cause of the common cold, contains a positive-sense strand of RNA which is translated into a large polyprotein in infected cells [3].
• In the case of HRVs, these small single-stranded positive-sense RNA viruses translate their genetic information into a polyprotein precursor which is further processed mainly by two viral proteases designated 2A and 3C [4].

High impact information on HRVBgp1

• Most maturation cleavages within the precursor polyprotein are mediated by rhinovirus 3C protease (or its immediate precursor, 3CD), a cysteine protease with a trypsin-like polypeptide fold [5].
• Nucleotide sequences coding for the complete polyprotein, the RNA polymerase, and VP1 were analyzed separately [6].
• Compound 1 inhibited HRV 3C-mediated polyprotein processing in infected cells in a concentration-dependent manner, providing direct confirmation that the cell-based antiviral activity is due to inhibition of 3C protease [7].
• Deletions in the 5' non-coding sequence modulated viral polyprotein synthesis significantly in a reticulocyte lysate system [8].
• The predicted amino acid sequence of the polyprotein shows close homology (88%) to that of the previously sequenced coxsackievirus B3 and to certain regions of the polyproteins of the polioviruses and human rhinovirus 14 [9].

Chemical compound and disease context of HRVBgp1

• Peptidyl diazomethyl ketones inhibit the human rhinovirus 3C protease: effect on virus yield by partial block of P3 polyprotein processing [10].

Biological context of HRVBgp1

• Comparison of the nucleotide sequence and the predicted amino acid sequence with those of the polioviruses reveals a surprising degree of homology which may allow recognition of regions of antigenic importance and prediction of the virus polyprotein cleavage sites [11].
• Excluding the poly(A) tract, the RNA genome is 7395 nucleotides in length and appears to encode a single polyprotein of 2183 amino acids [9].
• Human rhinovirus (HRV) is a positive-stranded RNA virus with an open reading frame that encodes for a single polyprotein of about 3000 amino acids [12].

Associations of HRVBgp1 with chemical compounds

• The enzyme activity of the purified protease was measured by cleavage of a synthetic peptide representing a predicted Gln/Gly viral polyprotein cleavage site [13].
• Several peptides mimicking the native 3C cleavage site of HRV-14 polyprotein have been synthesized with an N-acylated p-nitroaniline at position P1' and examined as substrates for the purified 3C protease [14].

Analytical, diagnostic and therapeutic context of HRVBgp1

• Western blot analysis of viral proteins from infected cells indicates that this inhibitor works specifically by blocking viral polyprotein maturation, displaying a reduction of detectable 3C protease and an accumulation of the 3CD polypeptide [10].

References