For the expression of their genes, viruses need the host transcriptional
machinery. There is a lot of evidence that suggests that cellular factors are
subverted by RNA viruses, many of which are used as replication factors or
translation machines for replication as well as transcription of viral RNAs. A
virus uses the host cell machinery, especially human transcription factors
(TFs), in order to synthesise its proteins. Therefore, we selected the TFs
involved in the development of various complex diseases. The main enzymes
responsible for coagulation as well as fibrinolysis, respectively, are thrombin
and plasmin. It was stated earlier that due to thrombin and plasmin factor Xa
along with trypsin, the infectivity of viruses with wild type SARS-spike
protein was lessened to a particular extent. Our objective in this
computational study was to investigate the interaction of human TFs with
thrombin, plasmin and cysteine protease through molecular docking,
including STAT1, TP53, NRF2, CALPAIN 10 and KCNJ11, respectively.
Therefore, we define the predicted interactions between these TFs and the
aforementioned molecules to infer the mechanism through which replication
of viral material can be indirectly prevented through inhibiting human TFs
using molecular docking analysis followed by molecular visualisation of
gleaned binding data. In accordance with the docking findings for
transcription factors, transcription factors that had a higher binding affinity
were selected and small molecules of cysteine protease had a higher binding affinity for E2F7, KCNJ11 thrombin and E2F7 plasmin. The actions of the transcription factors could be inhibited based on
potentially small molecule interactions and could serve as a potential target. In interfering with viral gene replication and synthesis,
these new perceptions into the roles of host proteins can be essential steps towards new, more powerful antivirals with fewer side
effects.
Keywords: Sars-CoV-2, Covid-19, Human Transcription Factors, Thrombin, Plasmin, Cysteine Protease, molecular docking