Volume 16, Issue 37, January - June, 2022

Antagonizing the interplay between SARS-CoV-2 viral RNA polymerase components and the host transcriptional machinery with Thrombin, Plasmin & Cysteine Protease as a potential mechanism of interference with viral RNA synthesis

Piyush Bhanu¹, Nisha Hemandhar Kumar², Sakshi Buchke³, Daniel Alex Anand⁴, Jitendra Kumar^5♦

¹Xome Life Sciences, Bangalore Bioinnovation Centre (BBC), Helix Biotech Park, Bengaluru, Karnataka- 560100, India
²Institute of Neuro and sensory physiology, University Medical Centre, Goettingen, Germany
³Xome Life Sciences, Bangalore Bioinnovation Centre (BBC), Helix Biotech Park, Bengaluru, Karnataka- 560100, India
⁴Department of Bioinformatics and The Centre for Molecular Data Science and Systems Biology, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu - 600119
⁵Bangalore Bioinnovation Centre (BBC), Helix Biotech Park, Electronics City Phase- 1, Bengaluru- 560100, Karnataka, India

^♦Corresponding author
Jitendra Kumar, Bangalore Bioinnovation Centre (BBC), Helix Biotech Park, Bengaluru, Karnataka - 560100

ABSTRACT

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

Drug Discovery, 2022, 16(37), 18-28

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