Key Event Description
A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. For example, the biological state being measured could be the activity of an enzyme, the expression of a gene or abundance of an mRNA transcript, the concentration of a hormone or protein, neuronal activity, heart rate, etc. The biological compartment may be a particular cell type, tissue, organ, fluid (e.g., plasma, cerebrospinal fluid), etc. The role in the biology could describe the reaction that an enzyme catalyses and the role of that reaction within a given metabolic pathway; the protein that a gene or mRNA transcript codes for and the function of that protein; the function of a hormone in a given target tissue, physiological function of an organ, etc. Careful attention should be taken to avoid reference to other KEs, KERs or AOPs. Only describe this KE as a single isolated measurable event/state. This will ensure that the KE is modular and can be used by other AOPs, thereby facilitating construction of AOP networks.
Coronavirus is a class of viruses which have single-stranded positive-sense RNA genomes in their envelopes [Cui J, et al. Nature Reviews Microbiology. 2019;17(3):181-192.]. Infected virus particles release their genomic RNA inside the human cells, followed by RNA translation or genomic RNA replication by RNA-dependent RNA polymerase (RdRp). RNA viral genome is transcribed into messenger RNA by viral RdRps [Ahlquist, P. Science 2002, 296, 1270, Florindo HF, Nature Nanotechnology. 2020:15(8):630-45.]. Viral RdRps act in combination with other viral and host factors involved in selecting template RNAs, elongating RNA synthesis, differentiating genomic RNA replication from mRNA transcription, modifying product RNAs with 5’ caps or 3’ polyadenylate [Ahlquist, P. Science 2002, 296, 1270]. Positive-sense (messenger-sense) RNA viruses replicate their genomes through negative-strand RNA intermediates [Schwartz, Michael et al. Molecular Cell. 2002;9(3):505-514]. Upon virus entry into host cells, genomic RNA serves as mRNA for the first open reading frame (ORF1), being thus translated into viral replicase polyproteins [Florindo HF, Nature Nanotechnology. 2020:15(8):630-45]. The cleaved-polyproteins assemble on double-membrane vesicles, where the RNA genome replication and subgenomic RNA transcription occur [Florindo HF, Nature Nanotechnology. 2020:15(8):630-45, Schwartz, Michael et al. Molecular Cell. 2002;9(3):505-514]. The RdRp complex uses the genome as a template to generate negative-sense subgenome and genome-length RNAs, which are in turn used as templates for synthesis of positive-sense full-length progeny genomes and subgenomic mRNAs [Hartenian E, et al. J Biol Chem. 2020;295(37):12910-12934].