Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

Comparative Domain-Fold Analysis of the SARS-CoV-2 ORF1ab Polyprotein: Insight into Co-Evolution, Conservation of Folding Patterns, Potential Therapeutic Strategies, and the Possibility of Reemergence

Version 1 : Received: 14 April 2020 / Approved: 16 April 2020 / Online: 16 April 2020 (16:13:13 CEST)

How to cite: Karmakar, S.; Kumar, S.; Katiyar, V. Comparative Domain-Fold Analysis of the SARS-CoV-2 ORF1ab Polyprotein: Insight into Co-Evolution, Conservation of Folding Patterns, Potential Therapeutic Strategies, and the Possibility of Reemergence. Preprints 2020, 2020040286 (doi: 10.20944/preprints202004.0286.v1). Karmakar, S.; Kumar, S.; Katiyar, V. Comparative Domain-Fold Analysis of the SARS-CoV-2 ORF1ab Polyprotein: Insight into Co-Evolution, Conservation of Folding Patterns, Potential Therapeutic Strategies, and the Possibility of Reemergence. Preprints 2020, 2020040286 (doi: 10.20944/preprints202004.0286.v1).

Abstract

The high transmissibility and replication of SARS-CoV-2 have been attributed to enhanced protein functions which are dependent on protein folding. Our in silico study endeavored to scrutinize SARS-CoV-2 ORF1ab by analyzing the conserved folding patterns of its transcribed proteins. Accordingly, the findings indicated that SARS-CoV-2 ORF1ab shares domain-specific fold-fingerprints with a spectrum of unrelated organisms. Closer observation revealed slight changes in folding patterns engendered with small variation in the intrinsic amino acid sequence. By correlating with the evolvability-potential of RNA-viruses and COVID-19 pandemic, we hypothesize that SARS-CoV-2 could undergo fast recombination with the host, SARS-CoV-2 minor variants and other viral species resulting in a reservoir of SARS-CoV-2 quasispecies. It is highly possible that natural selection will cause a future emergence of evolved SARS-CoV-2-descendants. Nonetheless, we hope that this insightful study will assist in elucidating SARS-CoV-2 protein functionalities, development of vaccines, and the possibility and nature of future emergence.

Subject Areas

SARS-CoV-2; domain-fold; evolutionary fingerprint; conserved domain; point mutation; recombination

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