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ORF8 protein in SARS-CoV-2 might be a non-canonical RNA dependent RNA polymerase (RdRp)
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  • Ramya Venkatesan,
  • Prakash Shyam Karuppiah,
  • Rajkumar Prabhakaran,
  • Vignesh Kalimuthu,
  • Sathya Priya Krishnamoorthy,
  • Sivabalan Sivasamy,
  • Kadalmani Balamuthu
Ramya Venkatesan
Bharathidasan University
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Prakash Shyam Karuppiah
VVD and Sons Private Limited
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Rajkumar Prabhakaran
VVD and Sons Private Limited
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Vignesh Kalimuthu
Bharathidasan University
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Sathya Priya Krishnamoorthy
Bharathidasan University
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Sivabalan Sivasamy
VVD and Sons Private Limited
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Kadalmani Balamuthu
Bharathidasan University
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Abstract

No current treatment options were successful in containing the ongoing pandemic COVID-19 caused by SARS-CoV-2. It is essential to understand the molecular players of SARS-CoV-2 to find a suitable treatment method and to develop an effective antiviral drug as early as possible. Global researchers have undertaken accelerated structural studies of key proteins involved in host-virus interaction, replication, and transcription. In silico studies support structural biologist with preliminary information to efficiently drive further studies and characterization. From the genome sequence, most SARS-CoV-2 annotated ORF has conserved sequence similar to SARS-CoV-1, except for ORF8 and ORF10. The function of ORF8 protein in SARS-CoV-2 is uncertain. Herein, we had modelled the ORF8 protein and studied its putative function using various substrates as probe to determine its biological significance. The modelled SARS-CoV-2 (mORF87A) protein shows IgG characteristic folds and thus may belong to IgG superfamily. Further, we studied the binding efficacy of various antiviral drugs against the modelled ORF8 of SARS-CoV-2 (mORF8) to repurpose the drug and to use them as a probe to study its function by studying the binding/active sites interaction. Remdesivir had the highest binding affinity to ORF8 protein of SARS-CoV-2. The high affinity of the adenosine analogue yields critical information about the non-canonical RNA dependent RNA polymerase (RdRp) function of ORF8 protein. We hypothesize that the ORF8 protein may be a non-canonical RdRp in SARS-CoV-2 with ability to bind to canonical nsp12 complex.