Biochim Biophys Acta Mol Basis Dis . Insights Into SARS-CoV-2 Genome, Structure, Evolution, Pathogenesis and Therapies: Structural Genomics Approach

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Biochim Biophys Acta Mol Basis Dis


. 2020 Jun 13;165878.
doi: 10.1016/j.bbadis.2020.165878. Online ahead of print.
Insights Into SARS-CoV-2 Genome, Structure, Evolution, Pathogenesis and Therapies: Structural Genomics Approach


Ahmad Abu Turab Naqvi ¹ , Kisa Fatima ² , Taj Mohammad ¹ , Urooj Fatima ³ , Indrakant K Singh ⁴ , Archana Singh ⁵ , Shaikh Muhammad Atif ⁶ , Gururao Hariprasad ⁷ , Gulam Mustafa Hasan ⁸ , Md Imtaiyaz Hassan ⁹



Affiliations

• PMID: 32544429
• DOI: 10.1016/j.bbadis.2020.165878

Abstract

The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present review looks to highlight the differences in genomic, proteomic, pathogenesis, and therapeutic strategies of SARS-CoV-2. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV-1 and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins was performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, makes available drugs ineffective.

Keywords: COVID-19; Comparative genomics; Drug target; Molecular basis of pathogenesis; Molecular evolution; SARS-CoV-2.