Abstract
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His6-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2.
Highlights
A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 as the causative agent of coronavirus disease-19 (COVID-19) that occurred first in Wuhan, Hubei province, China [1]
Viruses rely on the host machinery for the efficient infection and for the completion of the replication cycle, changing expression profiles of host genes and interactions with the host proteins can help the virus to evade the immune reaction after the infection, as it was observed in the case of SARS-CoV and SARS-CoV-2 infection, as well [2,3,4,5]
Neither stretches of homologous host-pathogen protein sequences (SSHHPS) analysis nor NetCorona webserver predicted SARS-CoV-2 3CLpro cleavage sites in bovine serum albumin (BSA) (Table S2), in agreement with this we found that BSA was not processed by the protease (Figure 5b)
Summary
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